Trials / Recruiting

RecruitingNCT03874052

Ruxolitinib in Combination With Venetoclax With and Without Azacitidine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Phase I Study to Evaluate Safety of Ruxolitinib in Combination With Azacitidine + Venetoclax in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Status: Recruiting
Phase: Phase 1
Study type: Interventional
Enrollment: 51 (estimated)

Sponsor: Jennifer Saultz · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of ruxolitinib when given together with venetoclax and compares the effect of ruxolitinib in combination with venetoclax to venetoclax and azacitidine in treating patients with acute myeloid leukemia (AML) that has come back (relapsed) or has not responded to treatment (refractory). Ruxolitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Azacitidine stops cells from making deoxyribonucleic acid and may kill cancer cells. It is a type of antimetabolite. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving ruxolitinib in combination with venetoclax and azacitidine may be safe, tolerable, and/or effective compare to ruxolitinib with venetoclax in treating patients with relapsed or refractory AML.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate an maximum-tolerated dose (MTD) for ruxolitinib in combination with Ia. Venetoclax (Arm 1); Ib. Venetoclax and azacitidine (Arm 2). SECONDARY OBJECTIVES: I. To assess the efficacy of the study treatment. II. To assess the duration of clinical response. III. To assess the duration of clinical benefit. IV. To assess survival in the absence of treatment failure, hematologic relapse, or progressive disease. V. To assess overall survival. VI. To assess overall acute toxicity and tolerability. VII. To assess the effect of ruxolitinib in combination with azacitidine + venetoclax on quality of life (QOL). EXPLORATORY OBJECTIVES: I. To assess in vitro kinase inhibitor sensitivity using participants' bone marrow (or peripheral blood). II. To characterize changes in disease using molecular techniques (potentially including next-generation sequencing and/or BH3 profiling). III. To assess the impact of changes in molecular disease features. IV. To determine the in vivo pharmacokinetics (PK)/pharmacodynamics (PD) parameters of the study drugs (Arm 1 only). OUTLINE: This is a dose-escalation study of ruxolitinib in combination with fixed dose venetoclax with and without azacitidine. Patients are assigned to 1 of 2 arms. ARM 1 (COMPLETE 04/04/2025): Patients receive ruxolitinib orally (PO) twice daily (BID) and venetoclax PO once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive additional cycles of ruxolitinib and venetoclax at the discretion of the sponsor-investigator. Patients also undergo a skin punch biopsy and echocardiography (ECHO) at screening and blood sample collection and bone marrow aspiration and biopsy throughout the study. ARM 2: Patients receive ruxolitinib PO BID, venetoclax PO QD, and azacitidine intravenously (IV) or subcutaneously (SC) on days 1-7 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO at screening and blood sample collection and bone marrow aspiration and biopsy throughout the study. After completion of study treatment, patients are followed up every 6 months for up to 2 years.

Conditions

Interventions

Type	Name	Description
DRUG	Azacitidine	Given IV or SC
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration and biopsy
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow aspiration and biopsy
PROCEDURE	Echocardiography Test	Undergo ECHO
PROCEDURE	Punch Biopsy	Undergo skin punch biopsy
OTHER	Questionnaire Administration	Ancillary studies
DRUG	Ruxolitinib	Given PO
DRUG	Venetoclax	Given PO

Timeline

Start date: 2019-08-16
Primary completion: 2027-12-31
Completion: 2027-12-31
First posted: 2019-03-14
Last updated: 2026-03-24

Locations

3 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT03874052. Inclusion in this directory is not an endorsement.