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Trial record 1 of 1 for:    NCT04521231
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A Study of Subcutaneous Blinatumomab Administration in Acute Lymphoblastic Leukemia (ALL) Patients

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ClinicalTrials.gov Identifier: NCT04521231
Recruitment Status : Recruiting
First Posted : August 20, 2020
Last Update Posted : May 13, 2024
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Description
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Brief Summary:
The study aims to evaluate the safety, efficacy, and tolerability of subcutaneous (SC) blinatumomab for treatment of Acute Lymphoblastic Leukemia (ALL), to determine the maximum tolerated dose (MTD), and recommended phase 2 dose(s) (RP2D) of SC administered blinatumomab. It will also conduct a clinical PK evaluation of SC1 and SC2 blinatumomab formulations.

Condition or disease Intervention/treatment Phase
B Cell Precursor Acute Lymphoblastic Leukemia Drug: Blinatumomab Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 125 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Open-label Study to Investigate the Safety, Efficacy, and Pharmacokinetics of Administration of Subcutaneous Blinatumomab for the Treatment of Adults With Relapsed or Refractory B Cell Precursor Acute Lymphoblastic Leukemia (R/R B-ALL)
Actual Study Start Date : January 4, 2021
Estimated Primary Completion Date : November 23, 2026
Estimated Study Completion Date : September 21, 2028

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Dose Escalation Phase: Blinatumomab Subcutaneous Formulation 1 (SC1)
Cohorts of at least 3 participants each will be treated with escalating doses of bilinatumomab to determine the maximum tolerated dose (MTD). The MTD will be defined as the dose for which the estimate of the toxicity rate from an isotonic regression (Yan et al, 2017) is closest to the target toxicity rate. Safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy will be assessed.
 Drug: Blinatumomab
Blinatumomab will be administered as a subcutaneous (SC) injection.
Other Names:
  • AMG 103
  • Blincyto®
Experimental: Dose Expansion Phase: Blinatumomab SC1
Up to 4 cohorts of participants with R/R B-ALL will be enrolled to the preliminary recommended phase 2 dose (RP2D) and schedule determined from dose escalation phase. Each cohort will aim to further assess safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy.
 Drug: Blinatumomab
Blinatumomab will be administered as a subcutaneous (SC) injection.
Other Names:
  • AMG 103
  • Blincyto®
Experimental: Ph-IIC: Clinical PK Evaluation of SC Blinatumomab Formulations
1 cohort of participants will be enrolled into the Ph-IIC arm. The clinical PK evaluation cohort (Ph-IIC) will be conducted to compare the PK of SC1 and SC2 formulations at the RP2D determined from the dose expansion phase, in participants with R/R B-ALL.
 Drug: Blinatumomab
Blinatumomab will be administered as a subcutaneous (SC) injection.
Other Names:
  • AMG 103
  • Blincyto®


Outcome Measures
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Primary Outcome Measures :
  1. Dose Escalation Phase: Number of participants who experience dose limiting toxicities (DLTs) [ Time Frame: Up to 29 days ]
  2. Dose Escalation Phase: Number of participants who experience one or more treatment-emergent adverse events (TEAEs) [ Time Frame: Up to approximately 28 weeks ]
  3. Dose Escalation Phase: Number of participants who experience one or more serious TEAEs [ Time Frame: Up to approximately 28 weeks ]
  4. Dose Escalation Phase: Number of participants who experience one or more treatment-related treatment-emergent adverse events [ Time Frame: Up to approximately 28 weeks ]
  5. Dose Escalation Phase: Number of participants who experience one or more adverse events (AEs) [ Time Frame: Up to approximately 28 weeks ]
  6. Dose Expansion Phase (R/R B-ALL): Number of participants who achieve complete remission (CR) [ Time Frame: Up to 68 days ]
  7. Dose Expansion Phase (R/R B-ALL): Number of participants who achieve complete remission with partial hematological recovery (CRh) [ Time Frame: Up to 68 days ]
  8. Phase 2 Ph-IIC: Maximum concentration (Cmax) of blinatumomab SC1 and SC2 [ Time Frame: Up to approximately 4 weeks ]
  9. Phase 2 Ph-IIC: Average concentration (Cavg) of blinatumomab SC1 and SC2 [ Time Frame: Up to approximately 4 weeks ]
  10. Phase 2 Ph-IIC: Time to reach maximum concentration (Tmax) of blinatumomab SC1 and SC2 [ Time Frame: Up to approximately 4 weeks ]
  11. Phase 2 Ph-IIC: Area under the concentration-time curve (AUC) of blinatumomab SC1 and SC2 [ Time Frame: Up to approximately 4 weeks ]

Secondary Outcome Measures :
  1. Dose Escalation Phase: Minimum concentration over the dosing interval (Cmin) of blinatumomab [ Time Frame: Up to approximately 28 weeks ]
  2. Dose Escalation Phase: Cmax of blinatumomab [ Time Frame: Up to approximately 28 weeks ]
  3. Dose Escalation Phase: Tmax of blinatumomab [ Time Frame: Up to approximately 28 weeks ]
  4. Dose Escalation Phase: AUC of blinatumomab [ Time Frame: Up to approximately 28 weeks ]
  5. Dose Escalation Phase and Phase 2 (Ph-IIC cohort): Number of participants who achieve CR/CRh [ Time Frame: Up to 68 days ]
  6. Dose Escalation, Dose Expansion, and Ph-IIC: Number of participants with incidence of anti-blinatumomab antibody formation [ Time Frame: Up to approximately 28 weeks ]
  7. Dose Expansion Phase: Cmin of blinatumomab [ Time Frame: Up to approximately 28 weeks ]
  8. Dose Expansion Phase: Cmax of blinatumomab [ Time Frame: Up to approximately 28 weeks ]
  9. Dose Expansion Phase: Tmax of blinatumomab [ Time Frame: Up to approximately 28 weeks ]
  10. Dose Expansion Phase: AUC of blinatumomab [ Time Frame: Up to approximately 28 weeks ]
  11. Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Relapse-Free Survival in participants who achieve CR/CRh within the first 2 cycles(R/R B-ALL) [ Time Frame: Up to 68 days ]
  12. Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Overall survival (OS) [ Time Frame: Up to approximately 28 weeks ]
  13. Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Duration of complete response [ Time Frame: Up to approximately 28 weeks ]
  14. Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Number of participants who experience one or more TEAEs [ Time Frame: Up to approximately 28 weeks ]
  15. Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Number of participants who experience one or more serious treatment-emergent adverse event [ Time Frame: Up to approximately 28 weeks ]
  16. Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Number of participants who experience one or more treatment-related treatment-emergent adverse events [ Time Frame: Up to approximately 28 weeks ]
  17. Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Number of participants who experience one or more AEs [ Time Frame: Up to approximately 28 weeks ]
  18. Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Summary scores of quality of life at each assessment as assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) [ Time Frame: Baseline (Day 1) up to approximately 28 weeks ]
  19. Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Change from baseline of quality of life as assessed by the EORTC QLQ-C30 [ Time Frame: Baseline (Day 1) up to approximately 28 weeks ]

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

Inclusion Criteria:

  • Aged 18 years or older.

  • Participants with B-precursor ALL with any of the following:

    • Either refractory to primary induction therapy or refractory to at least 1 salvage therapy OR

    • In untreated first, second, third or greater relapse or refractory relapse

      • First Relapse is defined as achievement of first Complete Remission (CR) [CR1] during upfront therapy then relapse during or after continuation therapy
      • Primary Refractory disease is defined as the absence of CR after standard induction therapy
      • Refractory relapse is defined as lack of CR after salvage treatment
      • Second relapse or later relapse is defined as relapse after achieving a second CR (CR2) in first or later salvage
      • Refractory to salvage is defined as no attainment of CR after salvage
  • Relapsed or Refractory at any time after first salvage therapy.
  • Relapse at any time after allogenic hematopoietic stem cell transplant (HSCT).
  • Greater than or equal to 5% blasts in the Bone Marrow (Exception: Isolated Non-central nervous system (CNS) extramedullary disease [EMD]).
  • Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2.
  • Participants with relapse or refractory B Cell ALL Ph+ disease and that are intolerant or refractory to prior tyrosine kinase inhibitors (TKIs) are eligible.

The above is a summary, other inclusion criteria details may apply.

Exclusion Criteria:

  • Active ALL in the central nervous system (CNS). Presence of greater than 5 white blood cells per cubic millimeter in cerebrospinal fluid (CSF) with lymphoblasts present and/or clinical signs of CNS leukemia.
  • History or presence of clinically relevant CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis or severe (≥ grade 3) CNS events including immune effector cell-associated neurotoxicity syndrome (ICANS) from prior chimeric antigen receptor T-cell (CAR T) or other T cell engager therapies.
  • Isolated Extramedullary (EM) Disease
  • Symptoms and/or signs that indicate an acute or uncontrolled chronic infection, any other disease or condition that could be exacerbated by the treatment or would complicate protocol compliance.
  • Testicular leukemia
  • History of malignancy (with certain exceptions) other than ALL within 3 years prior to start of protocol-specified therapy.
  • Allogeneic HSCT within 12 weeks before the start of protocol-specified therapy.
  • Cancer chemotherapy within 2 weeks before the start of protocol-specified therapy (with certain exceptions).
  • Immunotherapy within 4 weeks before start of protocol-specified therapy. Prior failed cluster of differentiation (CD19) directed therapy such as prior blinatumomab or CD19 CAR T cells will be allowed, if treatment ended more than 4 weeks prior to start of protocol therapy therapy and no prior CNS complications.
  • Currently receiving treatment in or less than 30 days since ending treatment on another investigational study(ies).
  • Abnormal screening laboratory parameters.
  • Female participant: Expected to breastfeed during treatment and for 96 hours after the last dose of treatment.

The above is a summary, other exclusion criteria details may apply.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04521231


Contacts
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Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

Locations
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Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
More Information
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Additional Information:

Publications:

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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT04521231    
Other Study ID Numbers: 20180257
2019-004780-52 ( EudraCT Number )
First Posted: August 20, 2020    Key Record Dates
Last Update Posted: May 13, 2024
Last Verified: March 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
URL: https://www.amgen.com/datasharing

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Amgen:
R/R B-ALL
Blincyto®
AMG 103
Blinatumomab
Acute lymphoblastic leukemia (ALL)
Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Hematologic Diseases
 Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Blinatumomab
Antineoplastic Agents