Trials / Terminated

TerminatedNCT02420717

Ruxolitinib Phosphate or Dasatinib With Chemotherapy in Treating Patients With Relapsed or Refractory Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia

A Phase I-II Study of the Combination of Ruxolitinib or Dasatinib With Chemotherapy in Patients With Philadelphia Chromosome (Ph)-Like Acute Lymphoblastic Leukemia (ALL)

Status: Terminated
Phase: Phase 2
Study type: Interventional
Enrollment: 11 (actual)

Sponsor: M.D. Anderson Cancer Center · Academic / Other
Sex: All
Age: 10 Years
Healthy volunteers: Not accepted

Summary

This phase II trial studies the side effects and best dose of ruxolitinib phosphate and how well it works compared to dasatinib when given with chemotherapy in treating patients with Philadelphia chromosome-like acute lymphoblastic leukemia that has come back (relapsed) or has not responded to treatment (refractory). Ruxolitinib phosphate and dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving ruxolitinib phosphate or dasatinib with chemotherapy works better in treating patients with previously treated acute lymphoblastic leukemia.

Detailed description

PRIMARY OBJECTIVES: I. To determine the safety and maximal tolerated dose (MTD) of ruxolitinib phosphate (ruxolitinib) in combination with chemotherapy in patients with Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL). (Phase I, ruxolitinib cohort only) II. To determine the response rate (complete response \[CR\]/CR with incomplete marrow recovery \[CRi\]) of ruxolitinib or dasatinib in combination with chemotherapy in patients with Ph-like ALL. (Phase II) SECONDARY OBJECTIVES: I. To determine the response rate (CR/CRi) of ruxolitinib in combination with chemotherapy in patients with Ph-like ALL. (Phase I, ruxolitinib cohort only) II. To determine the duration of response, disease-free survival and overall survival of ruxolitinib in combination with chemotherapy in patients with Ph-like ALL. (Phase I, ruxolitinib cohort only) III. To determine the safety and toxicity profile of ruxolitinib or dasatinib in combination with chemotherapy in patients with Ph-like ALL. (Phase II) IV. To determine the duration of response, disease-free survival and overall survival of ruxolitinib or dasatinib in combination with chemotherapy in patients with Ph-like ALL. (Phase II) OUTLINE: This is a phase I, dose escalation study of ruxolitinib followed by a phase II study. Patients are assigned to 1 of 2 cohorts. COHORT A: Patients receive ruxolitinib phosphate orally (PO) twice daily (BID). Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. COHORT B: Patients receive dasatinib PO once daily (QD). Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. INTENSIVE CHEMOTHERAPY: After cycle 1, patients not achieving a response also receive cyclophosphamide intravenously (IV) over 3 hours BID on days 1-3, doxorubicin IV over 24-48 hours on day 4, vincristine IV over 30 minutes on days 4 and 11, and dexamethasone PO QD or IV over 30 minutes on days 1-4 and 11-14 of cycles 1, 3, 5, and 7. Patients receive methotrexate IV over 24 hours on day 1, leucovorin IV over 1 hour or PO every 6 hours on days 2-5, cytarabine IV over 2 hours BID on days on days 2 and 3 of cycles 2, 4, 6, and 8. At the discretion of the treating physician, patients may also receive rituximab IV over several hours on days 1 and 11 of cycles 1 and 3 and on days 1 and 8 of cycles 2 and 4 only. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive mercaptopurine PO thrice daily (TID), methotrexate PO once a week, vincristine IV over 30 minutes on day 1, and prednisone PO on days 1-5. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days.

Conditions

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	Given IV
DRUG	Cytarabine	Given IV
DRUG	Dasatinib	Given PO
DRUG	Dexamethasone	Given PO or IV
DRUG	Doxorubicin	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Leucovorin	Given IV or PO
DRUG	Mercaptopurine	Given PO
DRUG	Methotrexate	Given IV and PO
DRUG	Prednisone	Given PO
BIOLOGICAL	Rituximab	Given IV
DRUG	Ruxolitinib Phosphate	Given PO
DRUG	Vincristine	Given IV

Timeline

Start date: 2015-07-15
Primary completion: 2021-01-20
Completion: 2021-01-20
First posted: 2015-04-20
Last updated: 2025-06-08
Results posted: 2022-05-02

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT02420717. Inclusion in this directory is not an endorsement.