Phase 2 Trial of Blinatumomab in Philadelphia Positive/BCR-ABL Positive Acute Lymphoblastic Leukemia

Overview

About this study

This study seeks adult subjects with R/R Ph+ B-precursor ALL. 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 subjects), and a safety follow-up visit 30 days after treatment. Following the safety follow-up visit, subjects will be followed for response duration and survival every 3 months for 18 months or death, whichever occurs first.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

Patients with Ph+ B-precursor ALL, with any of the following:
- Relapsed or refractory to at least one second generation 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

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location	Status	Contact
Rochester, Minn. Mayo Clinic principal investigator Mark Litzow, M.D.	Closed for enrollment	Contact information: Cancer Center Clinical Trials Referral Office 855-776-0015

Mayo Clinic Location

Status

Contact

Rochester, Minn.

Mayo Clinic principal investigator

Mark Litzow, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Blinatumomab is a BiTE immuno-oncology therapy indicated for the treatment of patients with relapsed or refractory (r/r) B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). Aims To assess the efficacy and safety of blinatumomab as first salvage versus second or later salvage in patients with r/r BCP ALL. Materials & Methods Patient-level pooled data were used for this analysis. In total, 532 adults with r/r BCP ALL treated with blinatumomab were included (first salvage, n = 165; second or later salvage, n = 367). Results Compared with patients who received blinatumomab as second or later salvage, those who received blinatumomab as first salvage had a longer median overall survival (OS; 10.4 vs. 5.7 months; HR, 1.58; 95% CI, 1.26-1.97; P < .001) and relapse-free survival (10.1 vs. 7.3 months; HR, 1.38; 95% CI, 0.98-1.93; P = .061), and higher rates of remission (n = 89 [54%] vs. n = 150 [41%]; odds ratio, 0.59; 95% CI, 0.41-0.85; P = .005), minimal residual disease response (n = 68 [41%] vs. n = 118 [32%]), and allogeneic hematopoietic stem cell transplant (alloHSCT) realization (n = 60 [36%] vs. n = 88 [24%]), and alloHSCT in continuous remission (n = 33 [20%] vs. n = 52 (14%]). In a subgroup analysis, there was no apparent effect of prior alloHSCT on median OS in either salvage group. The safety profile of blinatumomab was generally similar between the groups; however, cytokine release syndrome, febrile neutropenia, and infection were more frequent with second or later salvage than with first salvage. Discussion In this pooled analysis, the logistic regression analyses indicated greater benefit with blinatumomab as first salvage than as second or later salvage, as evident by the longer median OS, longer median RFS, and higher rates of remission. Conclusion Overall, blinatumomab was beneficial as first salvage and as second or later salvage, but the effects were favorable as first salvage. Read More on PubMed
To evaluate long-term durability of blinatumomab, a BiTE® (bispecific T-cell engager) molecule, in adults with relapsed/refractory (R/R) Philadelphia chromosome-positive (Ph+) B-cell precursor acute lymphoblastic leukaemia (ALL). Read More on PubMed
Blinatumomab (BLINCYTO) is a novel bispecific T cell engager (BiTE) approved in the USA for the treatment of relapsed or refractory B cell precursor acute lymphoblastic leukemia (ALL) in children and adults, as well as minimal residual disease ALL in adults. This analysis characterized the population pharmacokinetics of intravenous blinatumomab in pediatric and adult patients. Read More on PubMed
The relationship between blinatumomab exposure and efficacy endpoints (occurrence of complete remission [CR] and duration of overall survival [OS]) or adverse events (occurrence of cytokine release syndrome [CRS] and neurological events) were investigated in adult patients with relapsed/refractory acute lymphoblastic leukaemia (r/r ALL) receiving blinatumomab or standard of care (SOC) chemotherapy to evaluate appropriateness of the blinatumomab dosing regimen. Read More on PubMed
Purpose Few therapeutic options are available for patients with Philadelphia chromosome-positive (Ph) B-precursor acute lymphoblastic leukemia (ALL) who progress after failure of tyrosine kinase inhibitor (TKI) -based therapy. Here, we evaluated the efficacy and tolerability of blinatumomab in patients with relapsed or refractory Ph ALL. Patients and Methods This open-label phase II study enrolled adults with Ph ALL who had relapsed after or were refractory to at least one second-generation or later TKI or were intolerant to second-generation or later TKIs and intolerant or refractory to imatinib. Blinatumomab was administered in 28-day cycles by continuous intravenous infusion. The primary end point was complete remission (CR) or CR with partial hematologic recovery (CRh) during the first two cycles. Major secondary end points included minimal residual disease response, rate of allogeneic hematopoietic stem-cell transplantation, relapse-free survival, overall survival, and adverse events (AEs). Results Of 45 patients, 16 (36%; 95% CI, 22% to 51%) achieved CR/CRh during the first two cycles, including four of 10 patients with the T315I mutation; 88% of CR/CRh responders achieved a complete minimal residual disease response. Seven responders (44%) proceeded to allogeneic hematopoietic stem-cell transplantation, including 55% (six of 11) of transplantation-naïve responders. Median relapse-free survival and overall survival were 6.7 and 7.1 months, respectively. The most frequent AEs were pyrexia (58%), febrile neutropenia (40%), and headache (31%). Three patients had cytokine release syndrome (all grade 1 or 2), and three patients had grade 3 neurologic events, one of which (aphasia) required temporary treatment interruption. There were no grade 4 or 5 neurologic events. Conclusion Single-agent blinatumomab showed antileukemia activity in high-risk patients with Ph ALL who had relapsed or were refractory to TKIs. AEs were consistent with previous experience in Ph ALL. Read More on PubMed