Clinical trial NCT02000427: Blinatumomab in Adults With Relapsed/Refractory Philadelphia Positive B-precursor Acute Lymphoblastic Leukemia
Official title: A Phase 2 Single Arm, Multicenter Trial to Evaluate the Efficacy of the BiTE Antibody Blinatumomab in Adult Subjects With Relapsed/Refractory Philadelphia Positive B-precursor Acute Lymphoblastic Leukemia (Alcantara Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Relapsed/Refractory Philadelphia Positive B-precursor ALL
Keywords: Relapsed; Refractory; Philadelphia Positive; B-precursor; Acute Lymphoblastic Leukemia; ALL; Blinatumomab; Leukemia;
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2013-12-04
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective is to evaluate the rate of complete remission/complete remission with partial hematological recovery (CRh\*) in adults with relapsed/refractory Philadelphia chromosome positive (Ph+) B-precursor acute lymphoblastic leukemia (ALL) who receive blinatumomab.

Detailed description: This is a single-arm Simon II stage design, multicenter study consisting of a screening period, an induction treatment period (2 cycles of blinatumomab), a consolidation treatment period (up to 3 additional cycles of blinatumomab for applicable participants), and a safety follow-up visit 30 days after treatment. Following the safety follow-up visit, participants will be followed for response duration and survival every 3 months for 18 months or death, whichever occurs first.

Eligibility criteria: Inclusion Criteria

* Patients with Ph+ B-precursor ALL, with any of the following:

  * Relapsed or refractory to at least one second generation tyrosine kinase inhibitor (TKI) (dasatinib, nilotinib, bosutinib, ponatinib)
  * OR intolerant to second generation TKI and intolerant or refractory to imatinib mesylate
* Greater than 5% blasts in bone marrow
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Age ≥ 18 years of age, at the time of informed consent.
* Subject has provided informed consent or subject's legally acceptable representative has provided informed consent when the subject has any kind of condition that, in the opinion of the Investigator, may compromise the ability of the subject to give written informed consent.

Exclusion Criteria

* History of malignancy other than ALL within 5 years prior to start of protocol-required therapy, except for adequately treated selected cancers without evidence of disease
* History or presence of clinically relevant central nervous system (CNS) pathology as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis
* Active ALL in the CNS or testes
* Isolated extramedullary disease
* Current autoimmune disease or history of autoimmune disease with potential CNS involvement
* Allogeneic hematopoietic stem cell transplantation (HSCT) within 12 weeks before blinatumomab treatment
* Active acute or extensive chronic graft-versus-host disease (GvHD) which included the administration of immunosuppressive agents to prevent or treat GvHD within 2 weeks before blinatumomab treatment
* immediately previous cancer chemotherapy, radiotherapy, or immunotherapy; and eligibility for allogeneic HSCT at the time of enrollment.

Primary outcomes:
measure: Percentage of Participants With Complete Remission/Complete Remission With Partial Hematological Recovery (CR/CRh*) During the First Two Treatment Cycles
timeFrame: Approximately 12 weeks, as of the data cut-off date of 20 May 2015
Secondary outcomes:
measure: Percentage of Participants With Minimal Residual Disease (MRD) Remission During the First 2 Cycles of Treatment
timeFrame: Approximately 12 weeks
measure: Duration of CR or CRh* Response
timeFrame: Up to the data cut-off date of 20 May 2015; median observation time was 7.0 months
measure: Percentage of Participants With Complete Remission (CR) During the First Two Treatment Cycles
timeFrame: Approximately 12 weeks, as of the data cut-off date of 20 May 2015
measure: Percentage of Participants With Complete Remission With Partial Hematological Recovery (CRh*) During the First Two Treatment Cycles
timeFrame: Approximately 12 weeks, as of the data cut-off date of 20 May 2015
measure: Percentage of Participants With Complete Remission/Complete Remission With Partial Hematological Recovery/Complete Remission With Incomplete Hematological Recovery (CR/CRh*/CRi) During the First Two Treatment Cycles
timeFrame: Approximately 12 weeks, as of the data cut-off date of 20 May 2015
measure: Overall Survival
timeFrame: From first dose of blinatumomab until the data cut-off date; median observation time was 8.8 months.
measure: Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT) During Blinatumomab Induced Remission
timeFrame: Up to the data cut-of date of 20 May 2015; Maximum duration on study was 14.5 months.
measure: 100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplant
timeFrame: From the date of allogeneic HSCT until the data cut-off date of 20 May 2015; median observation time was 3.2 months.
measure: Number of Participants With Adverse Events
timeFrame: From the first dose of blinatumomab until 30 days after the last dose, up to the cut-off date of 20 May 2015; the median duration of treatment was 53.8 days.
measure: Number of Participants Who Developed Anti-blinatumomab Antibodies
timeFrame: Day 29 of each treatment period and 30 days after the last dose
measure: Steady State Concentration of Blinatumomab
timeFrame: Cycle 1, day 8, 6 to 8 hours after the dose step to 28 μg/day, and Cycle 2, day 1, 6 to 8 hours after blinatumomab infusion
Other outcomes:
Locations:
city: Duarte
country: United States
facility: Research Site
state: California
city: La Jolla
country: United States
facility: Research Site
state: California
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: New York
country: United States
facility: Research Site
state: New York
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Houston
country: United States
facility: Research Site
state: Texas
city: Nantes Cedex 1
country: France
facility: Research Site
city: Paris Cedex 10
country: France
facility: Research Site
city: Toulouse cedex 9
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Frankfurt am Main
country: Germany
facility: Research Site
city: Würzburg
country: Germany
facility: Research Site
city: Bergamo
country: Italy
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Venezia
country: Italy
facility: Research Site
city: Verona
country: Italy
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Sutton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Martinelli G, Boissel N, Chevallier P, Ottmann O, Gokbuget N, Topp MS, Fielding AK, Rambaldi A, Ritchie EK, Papayannidis C, Sterling LR, Benjamin J, Stein A. Complete Hematologic and Molecular Response in Adult Patients With Relapsed/Refractory Philadelphia Chromosome-Positive B-Precursor Acute Lymphoblastic Leukemia Following Treatment With Blinatumomab: Results From a Phase II, Single-Arm, Multicenter Study. J Clin Oncol. 2017 Jun 1;35(16):1795-1802. doi: 10.1200/JCO.2016.69.3531. Epub 2017 Mar 29.
citation: Kuchimanchi M, Zhu M, Clements JD, Doshi S. Exposure-response analysis of blinatumomab in patients with relapsed/refractory acute lymphoblastic leukaemia and comparison with standard of care chemotherapy. Br J Clin Pharmacol. 2019 Apr;85(4):807-817. doi: 10.1111/bcp.13864. Epub 2019 Feb 18.
citation: Kantarjian HM, Zugmaier G, Bruggemann M, Wood BL, Horst HA, Zeng Y, Martinelli G. Impact of Blinatumomab Treatment on Bone Marrow Function in Patients with Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia. Cancers (Basel). 2021 Nov 9;13(22):5607. doi: 10.3390/cancers13225607.
citation: Clements JD, Zhu M, Kuchimanchi M, Terminello B, Doshi S. Population Pharmacokinetics of Blinatumomab in Pediatric and Adult Patients with Hematological Malignancies. Clin Pharmacokinet. 2020 Apr;59(4):463-474. doi: 10.1007/s40262-019-00823-8.
citation: Martinelli G, Boissel N, Chevallier P, Ottmann O, Gokbuget N, Rambaldi A, Ritchie EK, Papayannidis C, Tuglus CA, Morris JD, Stein A. Long-term follow-up of blinatumomab in patients with relapsed/refractory Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukaemia: Final analysis of ALCANTARA study. Eur J Cancer. 2021 Mar;146:107-114. doi: 10.1016/j.ejca.2020.12.022. Epub 2021 Feb 13.
citation: Topp MS, Stein AS, Gokbuget N, Horst HA, Boissel N, Martinelli G, Kantarjian H, Bruggemann M, Chen Y, Zugmaier G. Blinatumomab as first salvage versus second or later salvage in adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia: Results of a pooled analysis. Cancer Med. 2021 Apr;10(8):2601-2610. doi: 10.1002/cam4.3731. Epub 2021 Mar 18.
citation: Horst HA, Zugmaier G, Martinelli G, Mergen N, Velasco K, Zaman F, Kantarjian H. CD19-negative relapse in adult patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia following treatment with blinatumomab-a post hoc analysis. Am J Hematol. 2023 Aug;98(8):E222-E225. doi: 10.1002/ajh.26988. Epub 2023 Jun 22. No abstract available.
citation: Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704.