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Ruxolitinib With Azacitidine Maintenance for the Treatment of Patients With Acute Myeloid Leukemia Undergoing Reduced Intensity Allogeneic Stem Cell Transplantation

ConditionAcute Myeloid Leukemia
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorOHSU Knight Cancer Institute

About this trial

This phase I trial studies the side effects and best dose of ruxolitinib (Rux) therapy alone (monotherapy) followed by Rux plus azacitidine (AZA) maintenance therapy and to see how well it works in treating patients with acute myeloid leukemia (AML) who are undergoing reduced intensity allogeneic hematopoietic stem cell transplantation (alloHSCT). AlloHSCT provides the only chance for cure for many patients with AML. AlloHSCT is a procedure in which a person receives blood-forming stem cells (cells from which all blood cells develop) from a genetically similar, but not identical, donor. This is often a sister or brother, but could be an unrelated donor. One of the common reasons for death after an alloHSCT is graft versus host disease (GVHD), which occurs when the transplanted cells from the donor attacks the recipient's normal cells. Ruxolitinib is in a class of medications called kinase inhibitors. It works to treat GVHD by blocking the signals of the cells that cause GVHD. Azacitidine is in a class of medications called demethylation agents. It works by helping the bone marrow to produce normal blood cells and by killing abnormal cells in the bone marrow. Giving Rux after the transplant may stop GVHD from occurring. Maintenance therapy with AZA, may help prevent or delay cancer from coming back. Giving Rux monotherapy followed by Rux plus AZA maintenance therapy may be safe, tolerable, and/or effective in treating patients with AML who are undergoing alloHSCT.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

PART A: Willingness to provide written informed consent before any study-specific procedures or interventions are performed. For participants unable to independently provide consent, a legally authorized representative (LAR) must provide consent

PART A: Age ≥ 18 years, at the time of consent

PART A: All types and categories of AML, as defined by World Health Organization (WHO) 2022, excluding acute promyelocytic leukemia (APL)

PART A: In complete remission (CR) or complete remission with incomplete blood count recovery (CRi) after induction of remission for transition to transplant by European LeukemiaNet 2022 Risk Stratification (ELN 2022)

Disqualifiers

PART A: Patients with active central nervous system (CNS) involvement with AML. Prior diagnosis of CNS involvement of AML will be allowed if curatively treated

PART A: Patients with malabsorption syndrome or other condition that precludes oral route of drug administration

PART A: Patients with prior intolerance to any of the interventional study drugs or component of the formulations

PART A: Patients with prior failure of treatment with ruxolitinib

Trial design

Design model

Single group

Treatments tested in this trial

  • Allogeneic Hematopoietic Stem Cell Transplantation

    Procedure/Surgery

    Undergo alloHSCT

  • Azacitidine

    Drug

    Given IV

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Bone Marrow Aspiration

    Procedure/Surgery

    Undergo bone marrow aspiration

  • Bone Marrow Biopsy

    Procedure/Surgery

    Undergo bone marrow biopsy

  • Cyclophosphamide

    Drug

    Given IV

  • Echocardiography Test

    Procedure/Surgery

    Undergo ECHO

  • Electronic Health Record Review

    Other intervention

    Ancillary studies

  • Multigated Acquisition Scan

    Procedure/Surgery

    Undergo MUGA

  • Mycophenolate Mofetil

    Drug

    Given PO or IV

  • Reduced-Intensity Transplant Conditioning Procedure

    Other intervention

    Undergo SOC RIC or NMA conditioning

  • Ruxolitinib

    Drug

    Given PO

  • Survey Administration

    Other intervention

    Ancillary studies

  • Tacrolimus

    Drug

    Given PO or IV

Treatment groups

40 Participants
are divided into 1 treatment group
Group A: Treatment (ruxolitinib, azacitidine)Experimental treatment 14 interventions

Trial outcomes

Primary outcomes

1

Incidence of dose limiting toxicities (DLTs)

Will determine the safety and tolerability of ruxolitinib monotherapy (part A) and ruxolitinib plus azacitidine therapy (part B). DLTs will be used to identify a maximum tolerated dose. Dose levels will either be de-escalated, escalated, or retained-according to pre calculated Bayesian Optimal Interval decision rules.

Time frame
From cycle 1 day 1 (i.e., day +5 post-transplant) to end of cycle 2 (Cycle length = 28 days)
2

Incidence of grade 3+ treatment-related adverse events (TRAEs) (Part B)

TRAEs of grade 3 and higher experienced during treatment with the doublet of ruxolitinib + azacitidine will be reported (with frequencies and percentages) as a co-primary endpoint. TRAEs are defined as adverse events that are definitely or possibly attributable to study treatment. Will be assessed using Common Terminology Criteria for Adverse Events version 5.0, where adverse events are assessed on a scale of 1-5, with higher scores indicating worse outcomes.

Time frame
Up to 30 days after the end of cycle 9

Secondary outcomes

1

Graft versus host disease (GVHD)-free, relapse-free survival

Will be estimated by the Kaplan-Meier method, with estimates provided for the median time-to-event (with 95% log-log confidence interval \[CI\]) and event rates (and 95% log-log CIs) at landmark times like 3-, 6-, 12-, and 24-months post-allogeneic hematopoietic stem cell transplant (HSCT).

Time frame
From date of transplant to disease relapse, grade III-IV acute (a) GVHD, chronic (c) GVHD requiring systemic immunosuppressive therapy, or death from any cause or last known alive (censored), whichever occurs earlier, assessed up to 2 years
2

Overall survival

Will be estimated by the Kaplan-Meier method, with estimates provided for the median time-to-event (with 95% log-log CI) and event rates (and 95% log-log CIs) at landmark times like 3-, 6-, 12-, and 24-months post-allogeneic HSCT.

Time frame
From date of transplant to last known alive (censored) or death date, assessed up to 2 years
3

Cumulative incidence of neutrophil engraftment

Deaths in the absence of the event of interest will be considered as a competing risk. Cumulative incidence function (CIF) estimates will be provided with 95% CIs at landmark times (e.g., day +30, day +60, day +100) for each time-to-event endpoint with a competing risk.

Time frame
From date of transplant to 30 days post-HSCT
4

Cumulative incidence of platelet engraftment

Deaths in the absence of the event of interest will be considered as a competing risk. CIF estimates will be provided with 95% CIs at landmark times (e.g., day +30, day +60, day +100) for each time-to-event endpoint with a competing risk.

Time frame
From date of transplant to 100 days post-HSCT but prior to Part B

Other outcomes

Sponsors and contacts

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

OHSU Knight Cancer Institute

Lead sponsor

Incyte Corporation

Collaborator

Oregon Health and Science University

Collaborator

Source ClinicalTrials.gov
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