Clinical trial NCT01209286: Study of the BiTE® Blinatumomab (MT103) in Adult Patients With Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia (ALL)
Official title: An Open Label, Multicenter, Exploratory Phase II Study to Evaluate the Efficacy, Safety, and Tolerability of the BiTE® Antibody Blinatumomab in Adult Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: B-ALL
Keywords: Blinatumomab
B-ALL
adult ALL
relapsed ALL
refractory ALL
Leukemia
ALL
Lymphatic diseases
Lymphoproliferative disorders
bispecific antibody
anti-CD19
Immunotherapeutic treatment
Lead sponsor: Amgen Research (Munich) GmbH
Sponsor class: INDUSTRY
First posted: 2010-09-27
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether the bispecific T-cell engager blinatumomab is effective, safe and tolerable in the treatment of patients with relapsed/refractory B-precursor ALL.

Detailed description: Relapsed/refractory B-precursor ALL in adult patients is an aggressive malignant disease with dismal prognosis and unmet medical need. Additional therapeutic approaches are urgently needed. Blinatumomab is a bispecific single-chain antibody construct designed to link B cells and T cells resulting in T cell activation and a cytotoxic T cell response against CD19 expressing cells. The purpose of this study is to investigate the efficacy, safety and tolerability of different doses of the bispecific T-cell engager blinatumomab in adult patients with relapsed/refractory B-precursor ALL. Patrticipants will receive up to five 4-week cycles of intravenous blinatumomab treatment.

Eligibility criteria: Inclusion Criteria:

* Patients with B-precursor ALL relapsed after at least induction and consolidation or having refractory disease
* More than 5% blasts in bone marrow
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Life expectancy of ≥ 12 weeks

Exclusion Criteria:

* History or presence of clinically relevant central nervous system (CNS) pathology
* Infiltration of cerebrospinal fluid (CSF) by ALL
* Autologous/allogeneic hematopoietic stem cell transplantation (HSCT) within six weeks/three months prior to start of blinatumomab treatment
* Active Graft-versus-Host Disease (GvHD)
* Patients with Philadelphia chromosome (Ph)+ ALL eligible for treatment with dasatinib or imatinib
* Cancer chemotherapy within two weeks prior to start of blinatumomab treatment
* Immunotherapy (e.g. rituximab) within four weeks prior to start of blinatumomab treatment
* Infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive)
* Pregnant or nursing women
* Previous treatment with blinatumomab

Primary outcomes:
measure: Percentage of Participants With a Best Response of Complete Remission or Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment
timeFrame: Within the first 2 cycles of treatment, 12 weeks
Secondary outcomes:
measure: Percentage of Participants With a Best Response of Complete Remission Within 2 Cycles of Treatment
timeFrame: Within the first 2 cycles of treatment, 12 weeks
measure: Percentage of Participants With a Best Response of Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment
timeFrame: Within the first 2 cycles of treatment, 12 weeks
measure: Percentage of Participants With a Best Response of Partial Remission Within 2 Cycles of Treatment
timeFrame: Within the first 2 cycles of treatment, 12 weeks
measure: Percentage of Participants With a Minimal Residual Disease (MRD) Response During the Core Study
timeFrame: During the core study treatment period (up to 30 weeks).
measure: Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT) After Treatment With Blinatumomab
timeFrame: Up to the data cut-off date of 15 October 2012; maximum follow up time was 459 days
measure: Time to Hematological Relapse
timeFrame: Up to the data cut-off date of 15 October 2012; maximum follow up time was 459 days.
measure: Relapse-free Survival
timeFrame: Up to the data cut-off date of 15 October 2012; maximum follow up time was 459 days.
measure: Overall Survival
timeFrame: Up to the data cut-off date of 15 October 2012; maximum follow up time was 667 days.
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle; median treatment duration was 55.7 days.
measure: Steady State Blinatumomab Concentration
timeFrame: Samples were collected at predose and at 48 hours following start of infusion, when dose is escalated and on Days 8, 15, 22, and 29 of the first 2 cycles.
measure: Clearance of Blinatumomab
timeFrame: Samples were collected at predose and at 48 hours following start of infusion, when dose is escalated and on Days 8, 15, 22, and 29 of the first 2 cycles.
measure: Serum Cytokine Peak Levels
timeFrame: Samples were collected prior to treatment start (baseline), and at 2, 6, 24, and 48 hours after drug infusion start, and at these same time points when dose is escalated in each treatment cycle.
Other outcomes:
Locations:
city: Frankfurt
country: Germany
city: Freiburg
country: Germany
city: Hannover
country: Germany
city: Kiel
country: Germany
city: Münster
country: Germany
city: Regensburg
country: Germany
city: Tübingen
country: Germany
city: Ulm
country: Germany
city: Würzburg
country: Germany
Study officials:
affiliation: University of Wuerzburg
name: Max Topp, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nagele V, Kratzer A, Zugmaier G, Holland C, Hijazi Y, Topp MS, Gokbuget N, Baeuerle PA, Kufer P, Wolf A, Klinger M. Changes in clinical laboratory parameters and pharmacodynamic markers in response to blinatumomab treatment of patients with relapsed/refractory ALL. Exp Hematol Oncol. 2017 May 18;6:14. doi: 10.1186/s40164-017-0074-5. eCollection 2017.
citation: Zhu M, Wu B, Brandl C, Johnson J, Wolf A, Chow A, Doshi S. Blinatumomab, a Bispecific T-cell Engager (BiTE((R))) for CD-19 Targeted Cancer Immunotherapy: Clinical Pharmacology and Its Implications. Clin Pharmacokinet. 2016 Oct;55(10):1271-1288. doi: 10.1007/s40262-016-0405-4.
citation: Topp MS, Gokbuget N, Zugmaier G, Klappers P, Stelljes M, Neumann S, Viardot A, Marks R, Diedrich H, Faul C, Reichle A, Horst HA, Bruggemann M, Wessiepe D, Holland C, Alekar S, Mergen N, Einsele H, Hoelzer D, Bargou RC. Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia. J Clin Oncol. 2014 Dec 20;32(36):4134-40. doi: 10.1200/JCO.2014.56.3247. Epub 2014 Nov 10.