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

NCT03874052 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: STUDY00018238NCI-2019-03272
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Recurrent Acute Myeloid Leukemia; Recurrent Secondary Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Refractory Secondary Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicities (DLT) for each arm-specific combination

  Within each arm, patient-level toxicity events will be summarized by dose level, major organ category, and grade.

  Up to day 56 (of cycle 1 [cycle length = 28 days]) for non-hematologic DLT and up to day 42 (of cycle 1 [cycle length = 28 days]) for hematologic DLTs

Secondary Outcomes (9)

• Composite complete remission rate

  From first dose to end of cycle 2 (cycle length = 28 days)

• Clinical response rate

  From first dose to end of cycle 2 (cycle length = 28 days)

• Clinical benefit rate (CBR)

  From first dose to end of cycle 2 (up to 36 days)

• Duration of clinical response

  From first morphologic leukemia-free state or better to bone marrow blasts >= 5%, circulating blasts, or EMD, or date of last disease assessment, assessed up to 2 years

• Duration of clinical benefit

  From first SD or better to evidence of progressive disease, or date of last disease assessment, assessed up to 2 years

Study Arms (2)

Arm 1 (ruxolitinib, venetoclax)

EXPERIMENTAL

Patients receive ruxolitinib PO BID and venetoclax PO 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 ECHO at screening and blood sample collection and bone marrow aspiration and biopsy throughout the study. (COMPLETE 04/04/2025)

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Echocardiography Test; Procedure: Punch Biopsy; Other: Questionnaire Administration; Drug: Ruxolitinib; Drug: Venetoclax

Arm 2 (ruxolitinib,venetoclax, azacitidine)

EXPERIMENTAL

Patients receive ruxolitinib PO BID, venetoclax PO QD, and azacitidine IV or 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.

Drug: Azacitidine; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Echocardiography Test; Procedure: Punch Biopsy; Other: Questionnaire Administration; Drug: Ruxolitinib; Drug: Venetoclax

Interventions

Azacitidine DRUG

Given IV or SC

Also known as: 5 AZC, 5-AC, 5-Azacitidine, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza

Arm 2 (ruxolitinib,venetoclax, azacitidine)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm 1 (ruxolitinib, venetoclax); Arm 2 (ruxolitinib,venetoclax, azacitidine)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration and biopsy

Arm 1 (ruxolitinib, venetoclax); Arm 2 (ruxolitinib,venetoclax, azacitidine)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow aspiration and biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Arm 1 (ruxolitinib, venetoclax); Arm 2 (ruxolitinib,venetoclax, azacitidine)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Arm 1 (ruxolitinib, venetoclax); Arm 2 (ruxolitinib,venetoclax, azacitidine)

Punch Biopsy PROCEDURE

Undergo skin punch biopsy

Also known as: BIOPSY, PUNCH, Punch Biopsy of Skin

Arm 1 (ruxolitinib, venetoclax); Arm 2 (ruxolitinib,venetoclax, azacitidine)

Questionnaire Administration OTHER

Ancillary studies

Arm 1 (ruxolitinib, venetoclax); Arm 2 (ruxolitinib,venetoclax, azacitidine)

Ruxolitinib DRUG

Given PO

Also known as: INCB 018424, INCB-018424, INCB-18424, INCB18424, Oral JAK Inhibitor INCB18424

Arm 1 (ruxolitinib, venetoclax); Arm 2 (ruxolitinib,venetoclax, azacitidine)

Venetoclax DRUG

Given PO

Also known as: ABT 199, ABT-0199, ABT-199, ABT199, GDC 0199, GDC-0199, GDC0199, RG7601, Venclexta, Venclyxto

Arm 1 (ruxolitinib, venetoclax); Arm 2 (ruxolitinib,venetoclax, azacitidine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document
• Age \>= 18 years at time of informed consent. Persons of all genders and gender identities, and members of all races and ethnic groups will be included
• Morphologically documented relapsed/refractory (R/R) AML or R/R secondary AML (sAML) that has progressed after at least 1 prior therapy for AML
• Prior treatment with venetoclax and azacitidine is allowed
• Treatment with hydroxyurea will not be considered a line of therapy
• Patients with morphologically documented myelodysplastic syndrome (MDS) that has progressed on hypomethylating agent (HMA) therapy also will be considered if the patient is ineligible for induction with intensive chemotherapy (IC), defined for this study as meeting one or more of the following criteria:
• Severe cardiac disorder (e.g., congestive heart failure requiring treatment, left ventricular ejection fraction (LVEF) of ≤ 50%, or chronic stable angina)
• Severe pulmonary disorder, certified by the managing physician
• Creatinine clearance of \< 45 ml/min or
• Hepatic disorder with total bilirubin \> 1.5 x upper limit of normal (ULN)
• Eastern Cooperative Oncology Group (ECOG) equal to 2
• Other comorbidity(ies) judged to be incompatible with high dose chemotherapy by the managing physician will be considered, at the discretion of the principal investigator (PI)
• ECOG performance status 0 to 2
• Persons of childbearing potential (PCBP) must have a negative serum or urine pregnancy test within 14 days prior to start of study drug administration
• Patients must agree to use an adequate method of contraception while on study treatment and for 120 days after the last dose of ruxolitinib for Arm 1 and 6 months after the last dose of azacitidine for Arm 2

You may not qualify if:

• Diagnosis of acute promyelocytic leukemia (APL or AML M3 subtype)
• Active central nervous system involvement with AML
• Chemotherapy or therapy with a non-investigational agent other than a biologic intended to within 1 week of the planned start of study therapy, with the exception of hydroxyurea for cytoreduction of proliferative disease, or at the discretion of the principal investigator (PI)
• Therapy with a non-biologic investigational agent within 14 days or 5 half lives, whichever is longer, of the planned start of study therapy, or for the period recommended by the institution's research pharmacy service, or at the discretion of the PI
• Therapy with a biologic investigational or non-investigational agent (e.g., monoclonal antibody) within 30 days of the planned start of study therapy, or for the period recommended by the institution's research pharmacy service, or at the discretion of the PI
• Concurrent active malignancy with expected survival of less than 1 year, at the discretion of the investigator. For example, candidates with treated skin cancers, prostate cancer, breast cancer, etc. without metastatic disease are candidates for therapy since their expected survival exceeds that of relapsed or refractory AML
• Clinically significant graft versus host disease (GVHD) or active GVHD requiring initiation or escalation of treatment within 28-day screening period
• Participants with rapidly progressive disease (defined by blast count doubles within 48 hours) or organ dysfunction
• Documented cardiac insufficiency (e.g., symptomatic heart failure, left ventricular ejection fraction of ≤ 40%)
• Symptomatic shortness of breath or patient requires supplemental oxygen support
• Clinically significant coagulation abnormality, such as disseminated intravascular coagulation
• Known history of cerebrovascular accident, myocardial infarction, or intracranial hemorrhage within 2 months of enrollment
• Known clinically significant liver disease defined as ongoing drug-induced liver injury, chronic active hepatitis C (hepatitis C virus \[HCV\]), chronic active hepatitis B (hepatitis B virus \[HBV\]), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, portal hypertension, or history of autoimmune hepatitis
• Untreated HIV or active hepatitis C detectable by polymerase chain reaction (PCR), or chronic hepatitis B (patients positive for hepatitis B core antibody who are receiving intravenous immunoglobulin therapy \[IVIG\] are eligible if hepatitis B \[HepB\] PCR is negative)
• Per PI discretion, active infection that is not well controlled by antibacterial or antiviral therapy

Sponsors & Collaborators

• Jennifer Saultz: lead
• AbbVie: collaborator
• Incyte Corporation: collaborator
• Oregon Health and Science University: collaborator

Study Sites (3)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

SUSPENDED

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

RECRUITING

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

SUSPENDED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine; Specimen Handling; Biopsy; ruxolitinib; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Jennifer N. Saultz, MD

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: IND Holder

Study Record Dates

• First Submitted: January 10, 2019
• First Posted: March 14, 2019
• Study Start: August 16, 2019
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 24, 2026

Record last verified: 2026-03

Locations

US (3)