NCT02000427 · CITED IN SOURCE DOCUMENTS

Blinatumomab in Adults With Relapsed/Refractory Philadelphia Positive B-precursor Acute Lymphoblastic Leukemia

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2024-05-28

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.

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Percentage of Participants With Complete Remission/Complete Remission With Partial Hematological Recovery (CR/CRh*) During the First Two Treatment Cycles

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outcome · POSTED

Percentage of Participants With Minimal Residual Disease (MRD) Remission During the First 2 Cycles of Treatment

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outcome · POSTED

Duration of CR or CRh* Response

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outcome · POSTED

Percentage of Participants With Complete Remission (CR) During the First Two Treatment Cycles

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outcome · POSTED

Percentage of Participants With Complete Remission With Partial Hematological Recovery (CRh*) During the First Two Treatment Cycles

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outcome · POSTED

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

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outcome · POSTED

Overall Survival

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outcome · POSTED

Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT) During Blinatumomab Induced Remission

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outcome · POSTED

100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplant

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outcome · POSTED

Number of Participants With Adverse Events

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outcome · POSTED

Number of Participants Who Developed Anti-blinatumomab Antibodies

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outcome · POSTED

Steady State Concentration of Blinatumomab

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants will receive blinatumomab by continuous intravenous (CIVI) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for 2 cycles. Participants who achieve a complete remission or complete remission with partial or incomplete hematologic recovery within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of blinatumomab. The initial dose will be 9 μg/day for the first 7 days of treatment, increased to 28 μg/day starting on day 8 for all subsequent cycles of treatment.
intervention Names
Drug: Blinatumomab
label
Blinatumomab
type
EXPERIMENTAL

interventions

arm Group Labels
Blinatumomab
description
Blinatumomab is administered as a continuous intravenous infusion (CIV). A single cycle of blinatumomab treatment is 6 weeks in duration, which includes 4 weeks of blinatumomab followed by a 2-week treatment-free interval.
name
Blinatumomab
other Names
Blincyto®
AMG 103
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 45
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Participants were evaluated for efficacy at the end of each treatment cycle via a central bone marrow aspiration and local peripheral blood counts. Complete remission was defined as meeting all 3 of the following criteria: * less than or equal to 5% blasts in the bone marrow; * no evidence of disease * full recovery of peripheral blood counts: platelets \> 100,000/μl, and absolute neutrophil count (ANC) \> 1000/μl. Complete remission with partial hematological recovery (CRh\*) was defined as meeting all 3 of the following criteria: * less than or equal to 5% blasts in the bone marrow * no evidence of disease * partial recovery of peripheral blood counts: platelets \> 50,000/μl, and ANC \> 500/μl. Participants without a post-baseline disease assessment were considered non-responders.
measure
Percentage of Participants With Complete Remission/Complete Remission With Partial Hematological Recovery (CR/CRh*) During the First Two Treatment Cycles
time Frame
Approximately 12 weeks, as of the data cut-off date of 20 May 2015

secondary Outcomes

description
Bone marrow samples were evaluated for MRD remission by a central laboratory using bcr-abl fusion gene reverse transcription polymerase chain reaction (RT-PCR). An MRD response was defined as MRD \< 10\^-4 measured by PCR. Participants with no post-baseline MRD assessment were considered non-responders.
measure
Percentage of Participants With Minimal Residual Disease (MRD) Remission During the First 2 Cycles of Treatment
time Frame
Approximately 12 weeks
description
Duration of response was measured for participants in remission (CR/CRh\*), and was measured from the time the participant first achieved remission until first documented relapse or death from disease progression. Participants without a documented relapse (hematological or extramedullary) and who did not die were censored at the time of the last bone marrow assessment or the last survival follow-up visit to confirm remission. Participants who died without having reported hematological relapse or without showing any clinical sign of disease progression were censored on their date of death.
measure
Duration of CR or CRh* Response
time Frame
Up to the data cut-off date of 20 May 2015; median observation time was 7.0 months
description
Participants were evaluated for efficacy at the end of each treatment cycle via a central bone marrow aspiration and local peripheral blood counts. Complete remission was defined as meeting all 3 of the following criteria: * less than or equal to 5% blasts in the bone marrow; * no evidence of disease; * full recovery of peripheral blood counts: platelets \> 100,000/μl, and absolute neutrophil count (ANC) \> 1000/μl. Participants without a post-baseline disease assessment were considered non-responders.
measure
Percentage of Participants With Complete Remission (CR) During the First Two Treatment Cycles
time Frame
Approximately 12 weeks, as of the data cut-off date of 20 May 2015
description
Participants were evaluated for efficacy at the end of each treatment cycle via a central bone marrow aspiration and local peripheral blood counts. Complete remission with partial hematological recovery (CRh\*) was defined as meeting all 3 of the following criteria: * less than or equal to 5% blasts in the bone marrow; * no evidence of disease; * partial recovery of peripheral blood counts: platelets \> 50,000/μl, and ANC \> 500/μl. Participants without a post-baseline disease assessment were considered non-responders.
measure
Percentage of Participants With Complete Remission With Partial Hematological Recovery (CRh*) During the First Two Treatment Cycles
time Frame
Approximately 12 weeks, as of the data cut-off date of 20 May 2015
description
Efficacy was evaluated via a central bone marrow aspiration and local peripheral blood counts. Complete remission was defined as meeting the following criteria: * less than or equal to 5% blasts in the bone marrow; * no evidence of disease; * full recovery of peripheral blood counts: platelets \> 100,000/μl, and absolute neutrophil count (ANC) \> 1000/μl. Complete remission with partial hematological recovery was defined as meeting the following criteria: * less than or equal to 5% blasts in the bone marrow; * no evidence of disease; * partial recovery of peripheral blood counts: platelets \> 50,000/μl, and ANC \> 500/μl. Complete remission with incomplete hematologic recovery was defined as meeting all of the following criteria: * less than or equal to 5% blasts in the bone marrow; * no evidence of disease; * incomplete recovery of peripheral blood counts: platelets \> 100,000/μl or ANC \> 1000/μl. Participants without a post-baseline disease assessment were considered non-responders.
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
time Frame
Approximately 12 weeks, as of the data cut-off date of 20 May 2015
description
Overall survival was assessed from the date the participant received the first infusion of blinatumomab until death from any cause or the date of the last follow-up. Participants still alive at the data cut-off date were censored on the last documented visit date or the date of the last contact when the patient was last known to have been alive.
measure
Overall Survival
time Frame
From first dose of blinatumomab until the data cut-off date; median observation time was 8.8 months.
description
Participants who achieved remission (CR/CRh\*) during the first 2 cycles of treatment and received an allogeneic HSCT.
measure
Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT) During Blinatumomab Induced Remission
time Frame
Up to the data cut-of date of 20 May 2015; Maximum duration on study was 14.5 months.
description
The analysis of 100-day mortality after allogeneic HSCT was assessed for participants who received an allogeneic HSCT while in remission (CR/CRh\*) after 2 cycles of blinatumomab treatment and did not receive any additional antileukemic treatment. 100-day mortality after allogeneic HSCT was calculated relative to the date of allogeneic HSCT. The 100-day mortality rate after allogeneic HSCT was defined as the percentage of participants having died up to 100 days after allogeneic HSCT estimated using the estimated time to death in percent calculated by Kaplan-Meier methods. Participants alive were censored on the last documented visit date or the date of the last phone contact when the patient was last known to have been alive.
measure
100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplant
time Frame
From the date of allogeneic HSCT until the data cut-off date of 20 May 2015; median observation time was 3.2 months.
description
Adverse events (AEs) were graded for severity according to the CTCAE version 4.0, where Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE. Treatment-related adverse events (TRAEs) were those assessed by the investigator as possibly related to blinatumomab based on response to the question: Is there a reasonable possibility that the event may have been caused by blinatumomab or other protocol-specified therapies/procedures?
measure
Number of Participants With Adverse Events
time Frame
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.
description
Anti-blinatumomab binding antibodies were evaluated with a validated blinatumomab anti-drug antibody assay with the electrochemiluminescence detection technology.
measure
Number of Participants Who Developed Anti-blinatumomab Antibodies
time Frame
Day 29 of each treatment period and 30 days after the last dose
measure
Steady State Concentration of Blinatumomab
time Frame
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

Full study description

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.

Source references

references

citation
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pmid
28355115
type
BACKGROUND
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.
pmid
30645768
type
BACKGROUND
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.
pmid
34830762
type
BACKGROUND
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.
pmid
31679130
type
BACKGROUND
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.
pmid
33588145
type
BACKGROUND
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.
pmid
33734596
type
BACKGROUND
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.
pmid
37345570
type
BACKGROUND
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.
pmid
35622074
type
DERIVED