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

NCT07548983 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: STUDY00028015NCI-2025-09157
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• 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.

  From cycle 1 day 1 (day +5 post-transplant) to end of cycle 2 (Cycle length = 28 days)

• 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.

  Up to 30 days after last dose of study drug

Secondary Outcomes (12)

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

  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

• Overall survival

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

• Cumulative incidence of neutrophil engraftment

  From date of transplant to 30 days post-HSCT

• Cumulative incidence of platelet engraftment

  From date of transplant to 100 days post-HSCT

• Cumulative incidence of Blood and Marrow Transplant Clinical Trials Network grade 2-3 infections

  From date of transplant to 100 days post-HSCT

Study Arms (1)

Treatment (ruxolitinib, azacitidine)

EXPERIMENTAL

See Detailed Description.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Azacitidine; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Cyclophosphamide; Procedure: Echocardiography Test; Other: Electronic Health Record Review; Procedure: Multigated Acquisition Scan; Drug: Mycophenolate Mofetil; Other: Reduced-Intensity Transplant Conditioning Procedure; Drug: Ruxolitinib; Other: Survey Administration; Drug: Tacrolimus

Interventions

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Treatment (ruxolitinib, azacitidine)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

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

Treatment (ruxolitinib, azacitidine)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518, B-518, B518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR 138719, WR- 138719, WR-138719, WR138719

Treatment (ruxolitinib, azacitidine)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Treatment (ruxolitinib, azacitidine)

Mycophenolate Mofetil DRUG

Given PO or IV

Also known as: CellCept, MMF

Treatment (ruxolitinib, azacitidine)

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo alloHSCT

Also known as: Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic

Treatment (ruxolitinib, azacitidine)

Azacitidine DRUG

Given IV

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

Treatment (ruxolitinib, azacitidine)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

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

Treatment (ruxolitinib, azacitidine)

Reduced-Intensity Transplant Conditioning Procedure OTHER

Undergo SOC RIC or NMA conditioning

Also known as: Non-Myeloablative Conditioning, Reduced Intensity Conditioning, Reduced Intensity Conditioning/Reduced Toxicity Conditioning

Treatment (ruxolitinib, azacitidine)

Ruxolitinib DRUG

Given PO

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

Treatment (ruxolitinib, azacitidine)

Survey Administration OTHER

Ancillary studies

Treatment (ruxolitinib, azacitidine)

Tacrolimus DRUG

Given PO or IV

Also known as: FK 506, FK-506, FK506, Fujimycin, Hecoria, Prograf, Protopic, Tacforius

Treatment (ruxolitinib, azacitidine)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Treatment (ruxolitinib, azacitidine)

Electronic Health Record Review OTHER

Ancillary studies

Treatment (ruxolitinib, azacitidine)

Eligibility Criteria

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

You may qualify if:

• 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)
• PART A: Planned alloHSCT with granulocyte colony-stimulating factor mobilized peripheral blood stem cells (PBSCs) and pre transplant conditioning disease status assessment of CR or CRi, as defined by ELN 2022 criteria
• PART A: Patient is at high risk for relapse based on cytogenetics, MRD by next generation sequencing (NGS), and/or ELN 2022 definition of adverse risk disease per the opinion of the treating physician
• PART A: Patients must have an unrelated PBSC donor meeting study donor selection requirements
• PART A: Only RIC or NMA conditioning must be plan and patient is not a candidate for myeloablative conditioning (MAC). Post-transplant cyclophosphamide / tacrolimus / mycophenolate mofetil (PTCy/Tac/MMF) GVHD prophylaxis is planned with PTCy at 25 mg/kg/day on Day +3 and Day +4 post-HSCT
• Permitted conditioning regimens (per institutional protocol)
• Reduced-intensity conditioning:
• Fludarabine/ melphalan
• Dose reduction of melphalan to 100 rather than 140 are permitted at discretion of treating physician
• Non-Myeloablative Conditioning:
• Fludarabine/ busulfan/ total-body irradiation (TBI)
• Fludarabine/ TBI

You may not qualify if:

• 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
• PART A: Patients with history of any other malignancy within the 5 years prior to screening, with the exception of the following:
• Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
• Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
• Previous non-hematologic malignancy that has been successfully treated with curative intent (i.e., confined and surgically resected or treated with other modalities);
• Myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (only allowed if it transformed to AML and AML should be the indication for marrow transplantation)
• PART A: Patients with ejection fraction (EF) \< 40% and patients with New York Heart Association (NYHA) grade III or IV heart failure
• PART A: Patients with history of pulmonary embolism (PE) or myocardial infarction (MI) within the 6 months prior to cycle 1 day 1 (C1D1). Treated deep vein thromboses (DVTs) are allowed
• PART A: Patients with known history of stroke (including intracranial hemorrhage) within 60 days prior to start of conditioning
• PART A: Patients administered therapy with an investigational agent, a known JAK1/2 inhibitor (with the exception of ruxolitinib), or a SOC anti-cancer therapy, including chemotherapy and radiotherapy, within 5 half lives prior to C1D1, or per institutional practice
• PART A: Patients administered therapy with a biologic agent (e.g., a monoclonal antibody) for anti-neoplastic intent within 30 days prior to C1D1, or per the institutional practice
• PART A: Patients with known clinically significant liver disease defined as ongoing drug-induced liver injury, 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

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Incyte Corporation: collaborator
• Oregon Health and Science University: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Stem Cell Transplantation; Azacitidine; Specimen Handling; Biopsy; Cyclophosphamide; Mycophenolic Acid; ruxolitinib; Tacrolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; 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; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones

Study Officials

• Jennifer N Saultz

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 3, 2026
• First Posted: April 23, 2026
• Study Start (Estimated): May 20, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 29, 2028
• Last Updated: April 23, 2026

Record last verified: 2026-04

Locations

US (1)