NCT02484430

Sapanisertib in Treating Patients With Relapsed and/or Refractory Acute Lymphoblastic Leukemia

A Phase 2 Study of MLN0128 (TAK-228) in Relapsed and/or Refractory Acute Lymphoblastic Leukemia (ALL)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 16 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies how well sapanisertib works in treating patients with acute lymphoblastic leukemia that has returned after a period of improvement (relapsed) or has not responded to previous treatment (refractory). Sapanisertib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVES: I. To determine the complete hematologic response (CR)/complete response incomplete (CRi) rate when sapanisertib (MLN0128 \[TAK-228\]) is administered to adult patients with relapsed/refractory acute lymphoblastic leukemia (ALL). SECONDARY OBJECTIVES: I. To determine the overall response rate (CR, CRi/partial response (PR)/morphologic leukemia free state \[MLFS\]). II. To determine the CR/CRi duration when MLN0128 (TAK-228) is administered to adult patients with relapsed/refractory ALL. III. To determine the frequency of proceeding to allogeneic stem cell transplantation (SCT) for patients with relapsed/refractory ALL who achieve a response on MLN0128 (TAK-228). IV. To determine the overall survival for relapsed/refractory ALL patients on MLN0128 (TAK-228). TERTIARY OBJECTIVES: I. To examine the pharmacokinetics of MLN0128 (TAK-228) in ALL patients. II. To assess whether phosphorylation of the mTOR substrate 4EBP1 decreases in leukemic blasts harvested from the bone marrow on day 8 compared to baseline. III. To assess in an exploratory fashion whether MLN0128 (TAK-228) enhances expression of the pro-apoptotic proteins Bim and Puma in marrow ALL cells. IV. To assess in an exploratory fashion whether Mcl-1 levels decrease in blast cells during MLN0128 (TAK-228) treatment. V. To assess in an exploratory fashion whether a) the phospho-protein pattern at baseline or b) MLN0128 (TAK-228)-associated changes in the phospho-protein pattern differs between ALL samples that respond to therapy and those that do not. OUTLINE: Patients receive sapanisertib orally (PO) daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who are non-responders and in PR at the end of course 4 may receive sapanisertib PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months.

Conditions

• B Acute Lymphoblastic Leukemia
• B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1
• B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative
• Recurrent Adult Acute Lymphoblastic Leukemia
• Refractory Adult Acute Lymphoblastic Leukemia
• T Acute Lymphoblastic Leukemia

Interventions

Type	Name	Description
OTHER	Laboratory Biomarker Analysis	Correlative studies
OTHER	Pharmacological Study	Correlative studies
DRUG	Sapanisertib	Given PO

Timeline

• Start date: 2017-04-06
• Primary completion: 2018-12-28
• Completion: 2024-03-05
• First posted: 2015-06-29
• Last updated: 2025-03-03
• Results posted: 2022-05-24

Locations

14 sites across 1 country: United States

Regulatory

• FDA-regulated drug study