Design Of a Phase 1/2 Study Of Moxetumomab Pasudotox In Adult Patients With Relapsed and/Or Refractory Acute Lymphoblastic Leukemia (ALL)

Adult ALL encompasses a heterogeneous group of lymphoid malignancies. Long-term survival in adults is currently only 35% to 45%; the predominant reason for this is disease recurrence. Current outcomes of salvage chemotherapy for ALL are poor, with complete response rates of 20% to 30% depending on prior therapy and duration of first remission. Older patients with ALL who relapse have a very poor prognosis and very limited options. Thus, adults with relapsed/refractory ALL are a population with significant unmet needs, requiring effective salvage therapies that maintain durable remissions.

CD22 is expressed on most B-lineage ALL blasts; thus, it is an ideal target for eliminating leukemic cells. Moxetumomab pasudotox (MP) is a recombinant immunoconjugate composed of an anti-CD22 immunoglobulin variable domain genetically fused to a truncated form of Pseudomonasexotoxin, PE38. MP has been clinically tested and showed antitumor activity in other B-cell malignancies including relapsed hairy cell leukemia (Kreitman RJ, et al. J Clin Onc. 2012;30:1822-28) and pediatric ALL (Shah NN, et al. 2nd International Workshop on the Biology, Prevention, and Treatment of Relapse After HSCT Program and Abstract Book; Bethesda, MD. 2012. P-49).

This is a single-arm, open-label, phase 1/2, single-institution study of MP in relapsed and/or refractory adult patients with ALL. The phase 1 portion will determine the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of the regimen. The phase 2 portion will evaluate the clinical activity of the regimen as well as the tolerability and safety profile. The primary endpoints of the phase 1 are MTD and DLTs. In the phase 2, the primary endpoints are overall response, including complete remission (CR), CR without recovery of counts, and partial remission; the secondary endpoints are event-free survival (time from enrollment to relapse or death, or the last known follow-up) and overall survival at 2 years. MP will be administered intravenously over 30 minutes. The phase 1 will start with a 30 µg/kg dose every other day x 6 doses in a 21-day cycle; it will use a standard 3+3 dose escalation. Additional dose regimens may be investigated. The phase 2 starting dose will be the MTD from phase 1. Dosing will be discontinued upon disease progression, development of unacceptable toxicity, recommendation for alternate therapy, or patient noncompliance. Minimal residual disease at multiple time points and immunogenicity will be assessed. Enrollment will include a maximum of 60 patients.

This study will provide new insights into the treatment of adults with relapsed/refractory ALL as well as expand upon the clinical activity of MP previously demonstrated in B-cell malignancies.

This study is sponsored by MD Anderson Cancer Center. Collaborator: MedImmune. ClinicalTrials.gov Identifier: NCT01891981

Ravandi:MedImmune: Research Funding. Kantarjian:MedImmune: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; Bristol Myers-Squibb: Research Funding; Ariad: Research Funding. Goswami:MedImmune: Employment. Wang:MedImmune: Employment. Ibrahim:MedImmune: Employment.