A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-Cell Maturation Antigen (BCMA) in Participants With Relapsed or Refractory Multiple Myeloma (CARTITUDE-1)

• ClinicalTrials.gov Identifier: NCT03548207
• Recruitment Status: Completed
• First Posted: June 7, 2018
• Results First Posted: April 2, 2024
• Last Update Posted: April 2, 2024
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Study Description

Brief Summary:

The purpose of the study is to characterize safety of JNJ-68284528 and establish the recommended Phase 2 dose (RP2D) (Phase 1b) and to evaluate the efficacy of JNJ-68284528 (Phase 2).

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Biological: JNJ-68284528	Phase 1; Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Detailed Description:

This study will evaluate the safety and efficacy of JNJ-68284528. The study will include two phases. In Phase1b the study will enroll adults with multiple myeloma with interval assessments for potential dose escalation or de-escalation in subsequent participants. The dose selected at the completion of phase 1b will be used in Phase 2. Following consent, enrolled participants will undergo an apheresis procedure to collect cells for manufacture of investigational drug product (JNJ-68284528). Following manufacture of the drug product, participants will undergo lymphodepletion prior to infusion of JNJ-68284528. Participants will be followed for at least 2 years after study drug infusion, with long-term 15 year follow-up on a separate study. The study will evaluate safety, biomarkers, pharmacokinetic/pharmacodynamic evaluations and efficacy.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 126 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1b-2, Open-Label Study of JNJ-68284528, A Chimeric Antigen Receptor T-Cell (CAR-T) Therapy Directed Against BCMA in Subjects With Relapsed or Refractory Multiple Myeloma
• Actual Study Start Date: June 29, 2018
• Actual Primary Completion Date: August 23, 2022
• Actual Study Completion Date: August 23, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: JNJ-68284528; After lymphodepletion JNJ-68284528 will be administered as a single infusion.	Biological: JNJ-68284528; JNJ-68284528 consist of autologous T lymphocytes transduced with LCAR-B38M, a lentiviral vector to express a chimeric antigen receptor targeting the human B cell maturation antigen (anti-BCMA CAR).

Outcome Measures

Primary Outcome Measures :

1. Phase 1b: Number of Participants With Adverse Events as Per Severity [ Time Frame: Day 1 up to 45.2 months ]
   An AE was any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
2. Phase 2: Overall Response Rate (ORR) [ Time Frame: Day 1 up to 45.2 months ]
   ORR was defined as the percentage of participants who achieved partial response (PR) or better according to international myeloma working group (IMWG) criteria. IMWG criteria for PR: greater than or equal to (>=) 50 percent (%) reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to less than (<) 200 milligrams (mg) per 24 hours. If the serum and urine M-protein were not measurable, a decrease of >=50% in the difference between involved and uninvolved free light chain (FLC) levels was required in place of the M-protein criteria. If serum and urine M-protein were not measurable, and serum free light assay was also not measurable, >=50% reduction in bone marrow plasma cells (PCs) was required in place of M-protein, provided baseline bone marrow PC percentage was >=30%. In addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas was also required.

Secondary Outcome Measures :

1. Phase 2: Number of Participants With Adverse Events (AEs) as Per Severity [ Time Frame: Day 1 up to 45.2 months ]
   An AE was any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Severity was graded according to the NCI-CTCAE version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
2. Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-68284528 Transgene [ Time Frame: Pre and post dose on Day 1, and Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100, then every 4 weeks up to 1 year, and at the time of progressive disease or at study completion for participants without progressive disease (up to approximately 2.5 years) ]
   Maximum observed plasma concentration (Cmax) of JNJ-68284528 transgene was reported. Cmax was calculated in copies per microgram (mcg) genomic deoxyribonucleic acid (DNA).
3. Phase 1b and Phase 2: Actual Sampling Time of Last Measurable Analyte Concentration (Tlast) of JNJ-68284528 Transgene [ Time Frame: Pre and post dose on Day 1 and Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100, then every 4 weeks up to 1 year, and at the time of progressive disease or at study completion for participants without progressive disease (up to approximately 2.5 years) ]
   Tlast was defined as actual sampling time of last measurable (non-below quantification limit [BQL]) analyte concentration of JNJ-68284528 transgene.
4. Phase 1b and Phase 2: Area Under the Plasma Concentration Versus Time Curve From Time 0 To Last Measurable Concentration (AUC0-last) of JNJ-68284528 Transgene [ Time Frame: Pre and post dose on Day 1; Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100, then every 4 weeks up to 1 year, and at the time of progressive disease or at study completion for participants without progressive disease (up to approximately 2.5 years) ]
   Area under the plasma concentration versus time curve from time 0 to last measurable concentration of JNJ-68284528 transgene was reported.
5. Phase 1b and Phase 2: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinite Time (AUC0-infinity) of JNJ-68284528 Transgene [ Time Frame: Pre and post dose on Day 1 and Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100, then every 4 weeks up to 1 year, and at the time of progressive disease or at study completion for participants without progressive disease (up to approximately 2.5 years) ]
   Area under the plasma concentration versus time curve from time 0 to infinite time of JNJ-68284528 transgene was reported.
6. Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of CD3+CAR+ Cells in Blood After a Single Infusion of JNJ-68284528 [ Time Frame: Pre and post dose on Day 1 and Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100, then every 4 weeks up to 1 year, and at the time of progressive disease or at study completion for participants without progressive disease (up to approximately 2.5 years) ]
   Maximum observed plasma concentration (Cmax) of CD3+CAR+ Cells was reported. Cmax was calculated in cells per microliter.
7. Phase 1b and Phase 2: T Cell Persistence After a Single Infusion of JNJ-68284528 [ Time Frame: Pre and post dose on Day 1 and Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100, then every 4 weeks up to 1 year, and at the time of progressive disease or at study completion for participants without progressive disease (up to approximately 2.5 years) ]
   T Cell persistence after a single infusion of JNJ-68284528 was reported. T Cell persistence was defined as actual sampling time of last measurable (non-below quantification limit [BQL]) analyte concentration.
8. Phase 1b and Phase 2: Area Under the Plasma Concentration Versus Time Curve From Time 0 To Last Measurable Concentration (AUC0-last) of CD3+CAR+ Cells in Blood After a Single Infusion of JNJ-68284528 [ Time Frame: Pre and post dose on Day 1 and Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100, then every 4 weeks up to 1 year, and at the time of progressive disease or at study completion for participants without progressive disease (up to approximately 2.5 years) ]
   Area under the plasma concentration versus time curve from time 0 to last measurable concentration of CD3+CAR+ Cells was reported.
9. Phase 1b and Phase 2: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinite Time (AUC0-infinity) of CD3+CAR+ Cells in Blood After a Single Infusion of JNJ-68284528 [ Time Frame: Pre and post dose on Day 1 and Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100, then every 4 weeks up to 1 year, and at the time of progressive disease or at study completion for participants without progressive disease (up to approximately 2.5 years) ]
   Area under the plasma concentration versus time curve from time 0 to infinite time of CD3+CAR+ Cells in blood after a single infusion of JNJ-68284528 was reported.
10. Phase 1b and Phase 2: Mean Concentration of Soluble B-cell Maturation Antigen (BCMA) Levels in Serum After Single Infusion of JNJ-68284528 [ Time Frame: Days 352 and 1024 ]
    Mean concentration of soluble BCMA levels in serum after single infusion of JNJ-68284528 were reported.
11. Number of Participants With Depletion of BCMA Expressing Cells [ Time Frame: Pre dose (Day 1) up to 2 years ]
    Number of participants with depletion of BCMA expressing cells were reported.
12. Phase 1b and Phase 2: Serum Systemic Cytokine Concentrations [ Time Frame: Pre-infusion and 2 hours post infusion on Day 1, Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100 ]
    Serum systemic cytokine concentrations (Interleukin [IL]-6, IL-10, and Interferon Gamma [IFN-g]) were reported.
13. Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of CAR-T Cells (CD3+CAR+ Cells in Blood) After a Single Infusion of JNJ-68284528 [ Time Frame: Pre and post dose on Day 1 and Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100, then every 4 weeks up to 1 year, and at the time of progressive disease or at study completion for participants without progressive disease (up to approximately 2.5 years) ]
    Cmax of CAR-T cells (CD3+CAR+ cells in blood) after a single infusion of JNJ-68284528 was reported.
14. Phase 1b and Phase 2: Maximum T Cell Expansion After a Single Infusion of JNJ-68284528 [ Time Frame: Pre and post dose on Day 1 and Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100, then every 4 weeks up to 1 year, and at the time of progressive disease or at study completion for participants without progressive disease (up to approximately 2.5 years) ]
    Maximum T cell expansion was defined as maximum observed plasma concentration (Cmax) after a single Infusion of JNJ-68284528.
15. Phase 1b and Phase 2: Percentage of Participants With Positive Antibodies to JNJ-68284528 [ Time Frame: Pre dose (Day 1) up to 2 years ]
    Percentage of participants with positive antibodies to JNJ-68284528 were reported.
16. Phase 1b and Phase 2: Very Good Partial Response (VGPR) or Better Response Rate [ Time Frame: Pre dose (Day 1) up to 45.2 months ]
    VGPR or better response rate was defined as the percentage of participants who achieved VGPR or complete response (CR) (including stringent complete response [sCR]) according to the IMWG criteria during or after the study treatment. VGPR: Serum and urine component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein level less than (<) 100 mg/24 hour; CR: negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <5% PCs in bone marrow; sCR: CR in addition to having a normal free light chain (FLC) ratio and an absence of clonal cells in bone marrow by immunohistochemistry, immunofluorescence, 2-4 color flow cytometry.
17. Phase 1b and Phase 2: Minimal Residual Disease (MRD) Negative Rate [ Time Frame: Pre dose (Day 1) up to 45.2 months ]
    MRD negativity rate was defined as percentage of participants who had negative MRD by bone marrow aspirate at any timepoint after initial dose of JNJ-68284528 and before disease progression or starting subsequent therapy or retreatment with JNJ-68284528. MRD negativity rate was assessed by next-generation sequencing at a threshold of <10^5.
18. Phase 1b and Phase 2: Clinical Benefit Rate (CBR) [ Time Frame: Pre dose (Day 1) up to 45.2 months ]
    Clinical benefit rate was defined as the percentage of participants with best response of minimal response (MR) or better (including sCR, CR, VGPR, PR, and MR). MR was defined as >=25% but less than or equal to (<=) 49% reduction of serum M-protein and reduction in 24-hour urine M-protein by 50% to 89%. In addition to the above criteria, if present at baseline, >=50% reduction in the size of soft tissue plasmacytomas was also required.
19. Phase 1b and Phase 2: Duration of Response (DOR) [ Time Frame: Pre dose (Day 1) up to first documented PD or death (up to 45.2 months) ]
    DOR was defined as the time (in months) from the date of initial documented response (PR or better response) to the date of first documented evidence of progressive disease (PD) or death. PD is defined as an increase of 25% from the lowest response value in one of the following: serum and urine M-component (absolute increase must be >=0.5 gram per deciliter [g/dL] and >=200 mg/24 hours respectively); only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be >10 mg/dL); definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder, appearance of a new lesion(s), >=50% increase in circulating plasma cells if this was the only measure of disease.
20. Phase 1b and Phase 2: Time to First Response [ Time Frame: Pre dose (Day 1) up to 45.2 months ]
    Time to first response was defined as the time between date of the initial infusion of JNJ-68284528 and the first efficacy evaluation that the participant met all criteria for PR or better. IMWG criteria for PR: >=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or <200 mg per 24 hours, If the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria, If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow PCs is required in place of M-protein, provided baseline bone marrow plasma cell percentage was >=30%. In addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required.
21. Phase 1b and Phase 2: Progression-free Survival (PFS) [ Time Frame: Pre dose (Day 1) up to 45.2 months ]
    Progression-free survival was defined as the time from the date of the initial infusion of JNJ-68284528 to the date of first documented disease progression.
22. Phase 1b and Phase 2: Overall Survival [ Time Frame: Pre dose (Day 1) up to 45.2 months ]
    Overall survival was defined as the time from the date of the initial infusion of JNJ-68284528 to the date of the participant's death.
23. Phase 2 (US Population): Change From Baseline in EuroQol Five Dimension Questionnaire (EQ-5D-5L) Utility Score at Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296, 324, 352 and 380 [ Time Frame: Baseline, Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296, 324, 352 and 380 ]
    EQ-5D-5L was a 5-item questionnaire consisted of 2 components: a health state profile/a single utility index value and an optional VAS. EQ-5D health state profile/a single utility index value had 5 dimensions including mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension had 5 response levels: 1 =no problems, 2 =slight problems, 3 =moderate problems, 4 =severe problems and 5 =extreme problems. The scores for the 5 dimensions were used to compute a single utility score ranging from 0 to 1 representing the general health status of the individual. Higher score indicated better health status. EQ-5D VAS was used to record participant's rating for his/her "health today" and ranging from 0 to 100, where 0 = worst imaginable health state and 100 = best imaginable health state.
24. Phase 2 (Japan Population): Change From Baseline in EuroQol Five Dimension Questionnaire (EQ-5D-5L) Utility Score at Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296 and 324 [ Time Frame: Baseline, Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296 and 324 ]
    EQ-5D-5L was a 5-item questionnaire consisted of 2 components: a health state profile/a single utility index value and an optional VAS. EQ-5D health state profile/a single utility index value had 5 dimensions including mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension had 5 response levels: 1 =no problems, 2 =slight problems, 3 =moderate problems, 4 =severe problems and 5 =extreme problems. The scores for the 5 dimensions were used to compute a single utility score ranging from 0 to 1 representing the general health status of the individual. Higher score indicated better health status. EQ-5D VAS was used to record participant's rating for his/her "health today" and ranging from 0 to 100, where 0 = worst imaginable health state and 100 = best imaginable health state.
25. Phase 2 (US Population): Change From Baseline in EuroQol Five Dimension Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS) Score at Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296, 324, 352 and 380 [ Time Frame: Baseline, Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296, 324, 352 and 380 ]
    EQ-5D-5L was a 5-item questionnaire consisted of 2 components: a health state profile/a single utility index value and an optional VAS. EQ-5D health state profile/a single utility index value had 5 dimensions including mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension had 5 response levels: 1 =no problems, 2 =slight problems, 3 =moderate problems, 4 =severe problems and 5 =extreme problems. The scores for the 5 dimensions were used to compute a single utility score ranging from 0 to 1 representing the general health status of the individual. Higher score indicated better health status. EQ-5D VAS was used to record participant's rating for his/her "health today" and ranging from 0 to 100, where 0 =worst imaginable health state and 100 = best imaginable health state.
26. Phase 2 (Japan Population): Change From Baseline in EuroQol Five Dimension Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS) Score at Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296 and 324 [ Time Frame: Baseline, Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296 and 324 ]
    EQ-5D-5L was a 5-item questionnaire consisted of 2 components: a health state profile/a single utility index value and an optional VAS. EQ-5D health state profile/a single utility index value had 5 dimensions including mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension had 5 response levels: 1 =no problems, 2 =slight problems, 3 =moderate problems, 4 =severe problems and 5 =extreme problems. The scores for the 5 dimensions were used to compute a single utility score ranging from 0 to 1 representing the general health status of the individual. Higher score indicated better health status. EQ-5D VAS was used to record participant's rating for his/her "health today" and ranging from 0 to 100, where 0 = worst imaginable health state and 100 = best imaginable health state.
27. Phase 2 (US Population): Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 Subscales at Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296, 324, 352 and 380 [ Time Frame: Baseline, Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296, 324, 352 and 380 ]
    EORTC QLQ-C30 was a 30 items self-reporting questionnaire, with 1 week recall period, resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status scale (GHS), 3 symptom scales (fatigue, nausea and vomiting, and pain) and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Questionnaire includes 28 items with 4-point Likert type responses from "1-not at all" to "4-very much" to assess functioning and symptoms;2 items with 7-point Likert scales (1= poor and 7= excellent) for global health and overall health related QoL. Scores are transformed to 0 to 100 scale, with higher scores representing better GHS, better functioning, and more symptoms. Negative change from baseline values shows deterioration in quality of life or functioning and reduction in symptom and positive values indicate improvement and worsening of symptoms.
28. Phase 2 (Japan Population): Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 Subscales at Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296 and 324 [ Time Frame: Baseline, Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296 and 324 ]
    EORTC QLQ-C30 was a 30 items self-reporting questionnaire, with 1 week recall period, resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status scale (GHS), 3 symptom scales (fatigue, nausea and vomiting, and pain) and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Questionnaire includes 28 items with 4-point Likert type responses from "1-not at all" to "4-very much" to assess functioning and symptoms;2 items with 7-point Likert scales (1= poor and 7= excellent) for global health and overall health related QoL. Scores are transformed to 0 to 100 scale, with higher scores representing better GHS, better functioning, and more symptoms. Negative change from baseline values shows deterioration in quality of life or functioning and reduction in symptom and positive values indicate improvement and worsening of symptoms.
29. Phase 2: Change From Baseline in Patient Global Impression of Severity (PGIS) Score at Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296, 324, 352, 380 [ Time Frame: Baseline, Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296, 324, 352, 380 ]
    PGIS was a single item to assess severity of pain on a 5-point verbal rating scale ranged from 1 (no pain) to 5 (very severe pain), where 1: none; 2: mild; 3: moderate; 4: severe; 5: very severe. A higher score indicated a more severe pain.
30. Phase 2: Patient Global Impression of Change (PGIC) Score at Days 28, 56, 78, 100 [ Time Frame: Days 28, 56, 78, 100 ]
    PGIC was a single item to assess the participant's perception in change of their overall health status using a 7-point verbal rating scale ranging from 1(a lot better now) to 7 (a lot verse now), where 1: a lot better now; 2: moderately better now; 3: a little better now; 4: neither better nor worse; 5: a little worse now; 6: moderately worse now; 7: a lot worse now. Higher score indicated worse health status.
31. Phase 2 (US Population): Change From Baseline in EORTC QLQ-MY20 at Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296, 324, 352 and 380 [ Time Frame: Baseline, Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296, 324, 352 and 380 ]
    EORTC QLQ-MY20 scale comprised of 20 questions that addressed four myeloma-specific HRQoL domains: disease symptoms (includes bone aches or pain, back pain, hip pain, arm or shoulder pain, chest pain, and pain increasing with activity), side effects of treatment (includes drowsiness, thirst, feeling ill, dry mouth, hair loss, upset by hair loss, tingling hands or feet, restlessness/agitation, acid indigestion/heartburn, and burning or sore eyes), future perspective (includes worry about death and health in the future, and thinking about illness) and body image. The scale was administered to assess 4 single items: feel restless or agitated, thinking about your illness, worried about dying, worried about health in the future. Scores were averaged and scales were transformed on a 0 to 100 scale. A high score for side effects of treatment represented a high level of symptomatology or problems, whereas a high score for future perspective represented better outcomes.
32. Phase 2 (Japan Population): Change From Baseline in EORTC QLQ-MY20 at Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296 and 324 [ Time Frame: Baseline, Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296 and 324 ]
    EORTC QLQ-MY20 scale comprised of 20 questions that addressed four myeloma-specific HRQoL domains: disease symptoms (includes bone aches or pain, back pain, hip pain, arm or shoulder pain, chest pain, and pain increasing with activity), side effects of treatment (includes drowsiness, thirst, feeling ill, dry mouth, hair loss, upset by hair loss, tingling hands or feet, restlessness/agitation, acid indigestion/heartburn, and burning or sore eyes), future perspective (includes worry about death and health in the future, and thinking about illness) and body image. The scale was administered to assess 4 single items: feel restless or agitated, thinking about your illness, worried about dying, worried about health in the future. Scores were averaged and scales were transformed on a 0 to 100 scale. A high score for side effects of treatment represented a high level of symptomatology or problems, whereas a high score for future perspective represented better outcomes.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Have documented diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria
• Have measurable disease at Screening as defined by any of the following a) Serum monoclonal paraprotein (M-protein) level more than or equal to (>=) 1.0 gram per deciliter(g/dL) or urine M-protein level >=200 milligram per 24 hours (mg/24hr); or b) Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin free light chain 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio
• Have received at least 3 prior multiple myeloma treatment lines of therapy or are double refractory to an immunomodulatory drug (IMiD) and proteasome inhibitor (PI) (refractory multiple myeloma as defined by IMWG consensus criteria). Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single lines of therapy a) Undergone at least 1 complete cycle of treatment for each line of therapy, unless progressive disease (PD) was the best response to the regimen
• Have received as part of previous therapy a PI, an IMiD, and an anti-CD38 antibody
• Participant must have documented evidence of progressive disease based on investigator's determination of response by the IMWG criteria on or within 12 months of their last line of therapy. Confirmation may be from either central or local testing. Also, participants with documented evidence of progressive disease (as above) within the previous 6 months and who are refractory or non-responsive to their most recent line of therapy afterwards are eligible
• Have Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 or 1

Exclusion Criteria:

• Have received prior treatment with chimeric antigen receptor T (CAR-T) therapy directed at any target
• Have received any therapy that is targeted to B-cell maturation antigen (BCMA)
• Have following cardiac conditions: a) New York Heart Association (NYHA) stage III or IV congestive heart failure b) Myocardial infarction or coronary artery bypass graft (CABG) less than or equal to (<=) 6 months prior to enrollment c) History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration d) History of severe non-ischemic cardiomyopathy e) Impaired cardiac function (left ventricular ejection fraction [LVEF] less than [<]45%) as assessed by echocardiogram or multiple-gated acquisition (MUGA) scan (performed less than or equal to (<=) 8 weeks of apheresis)
• Received a cumulative dose of corticosteroids equivalent to >= 70 mg of prednisone within the 7 days prior to apheresis
• Have received either of the following: a) An allogenic stem cell transplant within 6 months before apheresis. Participants who received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft-versus-host disease (GVHD) b) An autologous stem cell transplant less than or equal to (<=) 12 weeks before apheresis
• Have known active, or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma

Contacts and Locations

Locations

United States, Arizona

Mayo Clinic Cancer Center-Scottsdale

Phoenix, Arizona, United States, 85054

United States, California

City of Hope

Duarte, California, United States, 91010

University of California San Francisco

San Francisco, California, United States, 94143

United States, Illinois

University of Chicago

Chicago, Illinois, United States, 60637

United States, Massachusetts

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02115

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

Massachusetts General Hospital

Boston, Massachusetts, United States, 02215

United States, Michigan

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

United States, Minnesota

Mayo Clinic Rochester

Rochester, Minnesota, United States, 55902

United States, Nebraska

University of Nebraska Medical Center

Omaha, Nebraska, United States, 68198

United States, New York

Mount Sinai Medical Center

New York, New York, United States, 10029

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

United States, North Carolina

Levine Cancer Institute

Charlotte, North Carolina, United States, 28204

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States, 15232

United States, Tennessee

Sarah Cannon Research Institute

Nashville, Tennessee, United States, 37203

United States, Wisconsin

Froedtert Memorial

Milwaukee, Wisconsin, United States, 53226

Japan

University Hospital Kyoto Perfectural University of Medicine

Kyoto, Japan, 602-8566

Nagoya City University Hospital

Nagoya, Japan, 467-8602

Hokkaido University Hospital

Sapporo-shi, Japan, 060-8648

Japanese Red Cross Medical Center

Shibuya, Japan, 150-8935

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

  Study Documents (Full-Text)

Documents provided by Janssen Research & Development, LLC:

Study Protocol  [PDF] June 15, 2022

Statistical Analysis Plan  [PDF] September 23, 2020

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Martin T, Lin Y, Agha M, Cohen AD, Htut M, Stewart AK, Hari P, Berdeja JG, Usmani SZ, Yeh TM, Olyslager Y, Goldberg JD, Schecter JM, Madduri D, Jackson CC, Deraedt W, Gries KS, Fastenau JM, Trudeau JJ, Akram M, Pacaud L, Jakubowiak A, Jagannath S. Health-related quality of life in patients given ciltacabtagene autoleucel for relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b-2, open-label study. Lancet Haematol. 2022 Dec;9(12):e897-e905. doi: 10.1016/S2352-3026(22)00284-8. Epub 2022 Oct 7.

Van Oekelen O, Aleman A, Upadhyaya B, Schnakenberg S, Madduri D, Gavane S, Teruya-Feldstein J, Crary JF, Fowkes ME, Stacy CB, Kim-Schulze S, Rahman A, Lagana A, Brody JD, Merad M, Jagannath S, Parekh S. Neurocognitive and hypokinetic movement disorder with features of parkinsonism after BCMA-targeting CAR-T cell therapy. Nat Med. 2021 Dec;27(12):2099-2103. doi: 10.1038/s41591-021-01564-7. Epub 2021 Dec 10.

Berdeja JG, Madduri D, Usmani SZ, Jakubowiak A, Agha M, Cohen AD, Stewart AK, Hari P, Htut M, Lesokhin A, Deol A, Munshi NC, O'Donnell E, Avigan D, Singh I, Zudaire E, Yeh TM, Allred AJ, Olyslager Y, Banerjee A, Jackson CC, Goldberg JD, Schecter JM, Deraedt W, Zhuang SH, Infante J, Geng D, Wu X, Carrasco-Alfonso MJ, Akram M, Hossain F, Rizvi S, Fan F, Lin Y, Martin T, Jagannath S. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet. 2021 Jul 24;398(10297):314-324. doi: 10.1016/S0140-6736(21)00933-8. Epub 2021 Jun 24. Erratum In: Lancet. 2021 Oct 2;398(10307):1216.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT03548207
• Other Study ID Numbers: CR108480; 2018-000121-32 ( EudraCT Number ); 68284528MMY2001 ( Other Identifier: Janssen Research & Development, LLC )
• First Posted: June 7, 2018
• Results First Posted: April 2, 2024
• Last Update Posted: April 2, 2024
• Last Verified: March 2024

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases