Study Evaluating the Safety and Efficacy of iR2 in Untreated and Unfit Elderly Patients With DLBCL

• ClinicalTrials.gov Identifier: NCT03949062
• Recruitment Status: Unknown
• First Posted: May 14, 2019
• Last Update Posted: February 17, 2021
• Sponsor: Ruijin Hospital
• Information provided by (Responsible Party): Zhao Weili, Ruijin Hospital

Study Description

Brief Summary:

This is a single-arm, open-label phase 2 study of iR2 in the treatment of unfit and elderly patients with untreated diffuse large B-cell lymphoma。

Condition or disease	Intervention/treatment	Phase
Diffuse Large B Cell Lymphoma	Drug: Ibrutinib; Drug: Lenalidomide; Drug: Rituximab	Phase 2

Detailed Description:

This open-label, single arm study will evaluate the efficacy and safety of ibrutinib， lenalidomide, rituximab (iR2) in previously untreated and unfit elderly subjects with diffuse large B-cell lymphoma. Subjects will receive 6 cycles of ibrutinib 560mg, day 1-21, orally (PO) , lenalidomide 25mg, day 1-10, rituximab 375mg/m2, intravenously, every 21 days.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Open-Label Study to Evaluate the Safety and Efficacy of iR2 (Ibrutinib，Lenalidomide, Rituximab）in Untreated and Unfit Elderly Patients With Diffuse Large B-cell Lymphoma
• Actual Study Start Date: March 13, 2019
• Estimated Primary Completion Date: March 2021
• Estimated Study Completion Date: May 2022

Arms and Interventions

Arm

Intervention/treatment

Experimental: iR2; Participants received six 21-day cycles of ibrutinib, lenalidomide, and rituximab (iR2) treatment (21-day cycles).

Drug: Ibrutinib; Ibrutinib 560mg per day administered orally on Day 1-21 of each 21-day cycle for 6 cycles; Other Name: Imbruvica; Drug: Lenalidomide; Lenalidomide 25mg per day administered orally on Day 1-10 of each 21-day cycle for 6 cycles; Other Name: Relvimid; Drug: Rituximab; Rituximab 375mg/m2 per day administered intraveneously on Day 1 of each 21-day cycle for 6 cycles; Other Name: Rituxan

Outcome Measures

Primary Outcome Measures :

1. Complete response rate [ Time Frame: At the end of Cycle 6 (each cycle is 21 days) ]
   Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria

Secondary Outcome Measures :

1. Overall response rate [ Time Frame: At the end of Cycle 6 (each cycle is 21 days) ]
   Percentage of participants with response(complete response and partial response) was determined on the basis of investigator assessments according to 2014 Lugano criteria
2. Progression free survival [ Time Frame: Baseline up to data cut-off (up to approximately 4 years) ]
   Progression-free survival was defined as the time from the date of diagnosis until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria, or death from any cause, whichever occurred first.
3. Overall survival [ Time Frame: Baseline up to data cut-off (up to approximately 4 years) ]
   Overall survival in the overall study population was defined as the time from the date of diagnosis to the date of death from any cause. Reported is the percentage of participants with event.
4. Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 [ Time Frame: Baseline up to data cut-off (up to approximately 4 years) ]
   An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Other Outcome Measures:

1. Circulating free Deoxyribonucleic Acid (cfDNA) monitoring [ Time Frame: Baseline up to data cut-off (up to approximately 4 years) ]
   cfDNA in peripheral blood assessed by local lab

Eligibility Criteria

• Ages Eligible for Study: 75 Years and older (Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Pathologically confirmed diffuse large B cell lymphoma, treatment naive
2. Age > 75 years
3. Ineligible for standard chemotherapy
4. Must has measurable lesion in CT or PET-CT prior to treatment
5. At least 3 months life expectation
6. Informed consented
7. No previous use of study drug

Exclusion Criteria:

1. Has accepted Chemotherapy before
2. Uncontrollable cardio-cerebral vascular, coagulative, autoimmune, serious infectious disease
3. Lab at enrollment (Unless caused by lymphoma): Neutrophile<1.5*10^9/L ;Platelet<80*10^9/L; ALT or AST >2*ULN; AKP or bilirubin >1.5*ULN ;Creatinine>1.5*ULN
4. Not able to comply to the protocol for mental or other unknown reasons Pregnant or lactation
5. HIV infection
6. If HbsAg positive, should check HBV DNA, DNA positive patients cannot be enrolled. If HBsAg negative but HBcAb positive (whatever HBsAb status), should check HBV DNA,DNA positive patients cannot be enrolled.
7. Other uncontrollable medical condition that may that may interfere the participation of the study

Contacts and Locations

Locations

China, Shanghai

Ruijin hospital

Shanghai, Shanghai, China, 200025

Sponsors and Collaborators

Ruijin Hospital

Investigators

• Study Chair: Weili Zhao, PhD; Ruijin Hospital

More Information

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

Xu PP, Shi ZY, Qian Y, Cheng S, Zhu Y, Jiang L, Li JF, Fang H, Huang HY, Yi HM, Ouyang BS, Wang L, Zhao WL. Ibrutinib, rituximab, and lenalidomide in unfit or frail patients aged 75 years or older with de novo diffuse large B-cell lymphoma: a phase 2, single-arm study. Lancet Healthy Longev. 2022 Jul;3(7):e481-e490. doi: 10.1016/S2666-7568(22)00123-4.

• Responsible Party: Zhao Weili, First Deputy Director，Hematology Department, Ruijin Hospital
• ClinicalTrials.gov Identifier: NCT03949062
• Other Study ID Numbers: NHL-iR2
• First Posted: May 14, 2019
• Last Update Posted: February 17, 2021
• Last Verified: February 2021

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

Keywords provided by Zhao Weili, Ruijin Hospital:

iR2

Additional relevant MeSH terms:

Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Rituximab; Lenalidomide; Ibrutinib; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Tyrosine Kinase Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action