We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Subcutaneous Blinatumomab Administration in Acute Lymphoblastic Leukemia (ALL) Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04521231
Recruitment Status : Recruiting
First Posted : August 20, 2020
Last Update Posted : June 24, 2022
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:
The study aims to evaluate the safety, efficacy, and tolerability of subcutaneous (SC) blinatumomab for treatment of Acute Lymphoblastic Leukemia (ALL) and to determine the maximum tolerated dose (MTD), and recommended phase 2 dose (RP2D) of SC administered blinatumomab.

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 105 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
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 : January 28, 2025
Estimated Study Completion Date : December 7, 2026


Arm Intervention/treatment
Experimental: Phase 1: Blinatumomab (Dose escalation)
Cohorts of at least 3 participants each will be treated with escalating doses of blinatumomab 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: Phase 2: Blinatumomab (Dose expansion)
Participants will be administered the recommend phase 2 dose (RP2D) determined from the dose escalation stage to further assess safety, pharmacokinetics (PK), pharmacodynamic (PD), and efficacy.
Drug: Blinatumomab
Blinatumomab will be administered as a subcutaneous (SC) injection.
Other Names:
  • AMG 103
  • Blincyto®




Primary Outcome Measures :
  1. Phase 1: Number of participants who experience dose limiting toxicities (DLTs) [ Time Frame: Up to 29 days ]
  2. Phase 1: Number of participants who experience one or more treatment-emergent adverse events (TEAEs) [ Time Frame: Up to approximately 28 weeks ]
  3. Phase 1: Number of participants who experience one or more serious TEAEs [ Time Frame: Up to approximately 28 weeks ]
  4. Phase 1: Number of participants who experience one or more treatment-related treatment-emergent adverse events [ Time Frame: Up to approximately 28 weeks ]
  5. Phase 1: Number of participants who experience one or more adverse events (AEs) [ Time Frame: Up to approximately 28 weeks ]
  6. Phase 2: Number of participants who achieve complete remission, complete remission with partial hematological recovery, or complete remission with incomplete hematological recovery (CR/CRh/CRi) [ Time Frame: Up to 68 days ]

Secondary Outcome Measures :
  1. Phase 1: Minimum concentration over the dosing interval (Cmin) of blinatumomab [ Time Frame: Up to approximately 28 weeks ]
  2. Phase 1: Maximum concentration (Cmax) of blinatumomab [ Time Frame: Up to approximately 28 weeks ]
  3. Phase 1: Time to reach maximum concentration (Tmax) of blinatumomab [ Time Frame: Up to approximately 28 weeks ]
  4. Phase 1: Area under the concentration-time curve (AUC) of blinatumomab [ Time Frame: Up to approximately 28 weeks ]
  5. Phase 1: Number of participants with incidence of anti-blinatumomab antibody formation [ Time Frame: Up to approximately 28 weeks ]
  6. Phase 1: Number of participants who achieve complete remission, complete remission with partial hematological recovery, and or complete remission with incomplete hematological recovery [ Time Frame: Up to 68 days ]
  7. Phase 2: Relapse-Free Survival in participants who achieve CR/CRh/CRi [ Time Frame: Up to 68 days ]
  8. Phase 2: Cmin of blinatumomab [ Time Frame: Up to approximately 28 weeks ]
  9. Phase 2: Cmax of blinatumomab [ Time Frame: Up to approximately 28 weeks ]
  10. Phase 2: Tmax of blinatumomab [ Time Frame: Up to approximately 28 weeks ]
  11. Phase 2: AUC of blinatumomab [ Time Frame: Up to approximately 28 weeks ]
  12. Phase 2: Cmin of blinatumomab (relapsed or refractory acute lymphoblastic leukemia participants only) [ Time Frame: Cycle 1 Day 1 (cycle is 34 days) ]
  13. Phase 2: Cmax of blinatumomab (relapsed or refractory acute lymphoblastic leukemia participants only) [ Time Frame: Cycle 1 Day 1 (cycle is 34 days) ]
  14. Phase 2: Tmax of blinatumomab (relapsed or refractory acute lymphoblastic leukemia participants only) [ Time Frame: Cycle 1 Day 1 (cycle is 34 days) ]
  15. Phase 2: AUC of blinatumomab (relapsed or refractory acute lymphoblastic leukemia participants only) [ Time Frame: Cycle 1 Day 1 (cycle is 34 days) ]
  16. Phase 2: Number of participants with incidence of anti-blinatumomab antibody formation [ Time Frame: Up to approximately 28 weeks ]
  17. Phase 2: Overall survival [ Time Frame: Up to approximately 28 weeks ]
  18. Phase 2: Duration of complete response [ Time Frame: Up to approximately 28 weeks ]
  19. Phase 2: Duration of minimal/measurable residual disease (MRD) response [ Time Frame: Up to approximately 28 weeks ]
  20. Phase 2: Number of participants who experience one or more TEAEs [ Time Frame: Up to approximately 28 weeks ]
  21. Phase 2: Number of participants who experience one or more serious treatment-emergent adverse event [ Time Frame: Up to approximately 28 weeks ]
  22. Phase 2: Number of participants who experience one or more treatment-related treatment-emergent adverse events [ Time Frame: Up to approximately 28 weeks ]
  23. Phase 2: Number of participants who experience one or more AEs [ Time Frame: Up to approximately 28 weeks ]
  24. Phase 2: 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 ]
  25. Phase 2: Change from baseline of quality of life 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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 first, second, third, or more than third 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.
  • 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 or psychosis.
  • 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.
  • 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 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.
  • 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.


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
Layout table for location contacts
Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

Locations
Show Show 21 study locations
Sponsors and Collaborators
Amgen
Investigators
Layout table for investigator information
Study Director: MD Amgen
Additional Information:
Layout table for additonal information
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: June 24, 2022
Last Verified: June 2022
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

Layout table for additional information
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:
Layout table for MeSH terms
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Blinatumomab
Antineoplastic Agents