NCT02323607

Pacritinib and Chemotherapy in Treating Patients With Acute Myeloid Leukemia and FLT3 Mutations

Phase I Study of Pacritinib and Chemotherapy in Patients With Acute Myeloid Leukemia and FLT3 Mutations

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 13 (actual)
• Sponsor: Bhavana Bhatnagar · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of pacritinib when given together with chemotherapy in treating patients with acute myeloid leukemia that have an abnormal change (mutation) in the fms-related tyrosine kinase 3 (FLT3) gene. Pacritinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine, daunorubicin hydrochloride, and decitabine, 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. Giving pacritinib and chemotherapy may be a better treatment for acute myeloid leukemia with FLT3 mutations.

Detailed description

PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability of pacritinib in combination with 7+3 or decitabine (respective cohorts are independent of each other) in patients with newly diagnosed or relapsed/refractory acute myeloid leukemia (AML) with FLT3 mutations. II. To define the specific toxicities, maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of these combinations. III. To determine the recommended phase 2 dose (RP2D) of these combinations. SECONDARY OBJECTIVES: I. To determine the rate and duration of complete remission (CR) +/- hematologic recovery of pacritinib and 7+3 or decitabine in AML. II. To determine the overall response rate (ORR) and disease free survival at 1 year. TERTIARY OBJECTIVES: I. To conduct pharmacokinetic studies of pacritinib in combination with chemotherapy. II. To determine the impact of pacritinib on the inhibition of Janus kinase 2 (JAK2), FLT3, AXL receptor tyrosine kinase (AXL), signal transducer and activator of transcription 5A (STAT5), spleen tyrosine kinase (Syk). III. To examine the exosome, cytokine, and chemokine changes of FLT3 down-stream inhibition by pacritinib. IV. To examine resistance patterns associated with treatment with pacritinib. V. To examine baseline cytogenetic, GTP binding protein overexpressed in skeletal muscle (GEM) signature, and long non-coding (Lnc) ribonucleic acid (RNA) signature and mutational status of the AML tumor cells to better identify subsets of patients with highest likelihood of responding to therapy. OUTLINE: This is a dose-escalation study of pacritinib. Patients are assigned to 1 of 2 treatment arms. COHORT A: INDUCTION: Patients receive pacritinib orally (PO) on days 1-21, cytarabine intravenously (IV) every 24 hours on days 5-11, and daunorubicin hydrochloride IV every 24 hours on days 5-7. Treatment repeats every 28 days for 1-2 courses in the absence of disease progression or unacceptable toxicity. COHORT B: INDUCTION: Patients receive pacritinib PO on days 1-21 and decitabine IV every 24 hours on days 5-14. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients achieving CR will proceed with transplant evaluation (if appropriate). Transplant-ineligible patients will receive maintenance courses of pacritinib PO on days 1-21 and decitabine IV over 1 hour daily on days 1-5. Maintenance courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for at least 30 days.

Conditions

• Recurrent Adult Acute Myeloid Leukemia
• Secondary Acute Myeloid Leukemia
• Therapy-Related Acute Myeloid Leukemia
• Untreated Adult Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Pacritinib	Given PO
DRUG	Cytarabine	Given IV
DRUG	Daunorubicin Hydrochloride	Given IV
DRUG	Decitabine	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
OTHER	Pharmacological Study	Correlative studies

Timeline

• Start date: 2016-01-12
• Primary completion: 2018-07-12
• Completion: 2018-07-12
• First posted: 2014-12-23
• Last updated: 2019-01-25

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study