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

ConditionsAcute Myeloid Leukemia Arising From Previous Myelodysplastic SyndromeRecurrent Acute Myeloid LeukemiaRecurrent Secondary Acute Myeloid LeukemiaRefractory Acute Myeloid LeukemiaRefractory Secondary Acute Myeloid Leukemia
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorJennifer Saultz

About this trial

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 compared to ruxolitinib with venetoclax in treating patients with relapsed or refractory AML.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Sequential

Treatments tested in this trial

  • Azacitidine

    Drug

    Given IV or SC

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Bone Marrow Aspiration

    Procedure/Surgery

    Undergo bone marrow aspiration and biopsy

  • Bone Marrow Biopsy

    Procedure/Surgery

    Undergo bone marrow aspiration and biopsy

  • Echocardiography Test

    Procedure/Surgery

    Undergo ECHO

  • Punch Biopsy

    Procedure/Surgery

    Undergo skin punch biopsy

  • Questionnaire Administration

    Other intervention

    Ancillary studies

  • Ruxolitinib

    Drug

    Given PO

  • Venetoclax

    Drug

    Given PO

Treatment groups

51 Participants
are divided into 2 treatment groups
Group A: Arm 1 (ruxolitinib, venetoclax)Experimental treatment 8 interventions
Group B: Arm 2 (ruxolitinib,venetoclax, azacitidine)Experimental treatment 9 interventions

Trial outcomes

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.

Time frame
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

1

Composite complete remission rate

Will be estimated, along with 95% confidence intervals (CIs).

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

Clinical response rate

Will be estimated, along with 95% CIs.

Time frame
From first dose to end of cycle 2 (cycle length = 28 days)
3

Clinical benefit rate (CBR)

CBR will be defined as the proportion of evaluable subjects obtaining stable disease (SD), partial remission, or composite complete remission during the first 2 cycles of therapy. Will be estimated, along with 95% CIs.

Time frame
From first dose to end of cycle 2 (up to 36 days)
4

Duration of clinical response

Time frame
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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Jennifer Saultz

Lead sponsor

OHSU Knight Cancer Institute

Sponsor institution

AbbVie

Collaborator

Incyte Corporation

Collaborator

Oregon Health and Science University

Collaborator

Source ClinicalTrials.gov
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