Dose-Expansion Study of Low Dose Post-Transplant Cyclophosphamide/Tacrolimus/Ruxolitinib for Graft-versus-Host Disease (GVHD) Prophylaxis in Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation

NCT07249346 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: OSU-24102
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, non-randomized, multicenter, pilot, dose expansion study of low dose post-transplant cyclophosphamide (25 mg/kg on Days +3 and +4)/tacrolimus/ruxolitinib in the setting of myeloablative conditioning (MAC) allogeneic peripheral blood stem cell transplantation (PBSCT).

Conditions

Leukemia; Myelodysplasia; Chronic Myelomonocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Severe acute GVHD-free Survival (SGFS)

  SGFS will be calculated from the time of transplant to onset of grade 3-4 acute GVHD or death censoring patients alive without grade 3-4 GVHD at last clinical assessment date. The SGFS rate together with 95% confidence interval at day 180 will be estimated by Kaplan-Meier method.

  At day 180 post-transplant

Secondary Outcomes (11)

• GVHD, relapse free survival (GRFS)

  At 6 months and 1 year

• Grade II-IV acute GVHD and Grade III-IV acute GVHD

  At 6 months

• Chronic GVHD requiring immunosuppression

  At 1 year

• GVHD Free Survival (GFS)

  At 1 year

• Hematologic Recovery (Neutrophil Counts)

  Up to 2 years post transplant

Study Arms (2)

Cohort 1 (Feasibility)

EXPERIMENTAL

Patients will receive post-transplant cyclophosphamide 25 mg/kg on Days +3 and +4, tacrolimus, and ruxolitinib for GVHD prophylaxis. Ruxolitinib will be dosed as ruxolitinib IR 5 mg po qD (on fluconazole, 5 mg po BID not on fluconazole) starting Day -1 until Day +28 and neutrophil engraftment and then increase to ruxolitinib IR 5 mg po BID (on fluconazole,10 mg po BID not on fluconazole) for up to 12 months. Tacrolimus will be tapered after Day +90 per institutional guidelines. Patients will receive ruxolitinib up to Day 180 posttransplant. Ruxolitinib will be tapered over 2-3 months depending on the starting dose at time of taper.

Drug: Ruxolitinib; Drug: Myeloablative conditioning regimen; Procedure: Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Drug: Tacrolimus

Cohort 2 (dose expansion)

EXPERIMENTAL

Patients will receive post-transplant cyclophosphamide 25 mg/kg on Days +3 and +4, tacrolimus, and ruxolitinib for GVHD prophylaxis. Ruxolitinib will be dosed as ruxolitinib IR 5 mg po qD (on fluconazole, 5 mg po BID not on fluconazole) starting Day -1 until Day +28 and neutrophil engraftment and then increase to ruxolitinib IR 5 mg po BID (on fluconazole,10 mg po BID not on fluconazole) for up to 12 months. Tacrolimus will be tapered after Day +90 per institutional guidelines. Patients will receive ruxolitinib up to Day 365 post-transplant. Ruxolitinib will be tapered over 2-3 months depending on the starting dose at time of taper.

Drug: Ruxolitinib; Drug: Myeloablative conditioning regimen; Procedure: Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Drug: Tacrolimus

Interventions

Ruxolitinib DRUG

Taken PO

Cohort 1 (Feasibility); Cohort 2 (dose expansion)

Myeloablative conditioning regimen DRUG

Patients will receive a full-intensity myeloablative conditioning regimen. Allowed regimens include: * Flu/Bu(130 mg/m2/day x 4 days) * Flu/TBI (8-12Gy) * Flu/Bu/Thiotepa The addition of alemtuzumab or ATG is not allowed.

Cohort 1 (Feasibility); Cohort 2 (dose expansion)

Hematopoietic Stem Cell Transplantation PROCEDURE

Patients will undergo HCT

Also known as: HCT

Cohort 1 (Feasibility); Cohort 2 (dose expansion)

Cyclophosphamide DRUG

Given IV

Cohort 1 (Feasibility); Cohort 2 (dose expansion)

Tacrolimus DRUG

Given PO

Cohort 1 (Feasibility); Cohort 2 (dose expansion)

Eligibility Criteria

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

You may qualify if:

• Age 18.0 years or older at the time of enrollment
• Patients undergoing allogeneic hematopoietic cell transplantation for one of the following indications:
• Acute leukemia with no circulating blasts and with less than 5% blasts in the bone marrow
• Myelodysplasia/chronic myelomonocytic leukemia with no circulating blasts and with less than 10% blasts in the bone marrow (higher blast percentage allowed in MDS due to lack of differences in outcomes with \<5% versus 5-10% blasts in this disease).
• Planned myeloablative (MAC) conditioning regimen (see eligible regimens in Section 9.2)
• Patients must have a related or unrelated peripheral blood stem cell donor as follows:
• Sibling donor must be a 6/6 match for HLA-A and -B at intermediate (or higher) resolution, and -DRB1 at high resolution using DNA-based typing and must be willing to donate peripheral blood stem cells and meet institutional criteria for donation.
• Unrelated donor must be an 8/8 match at HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing.
• Unrelated donor must be willing to donate peripheral blood stem cells and meet National Marrow Donor Program (NMDP) criteria for donation.
• \* Donor selection must comply with 21 CFR 1271
• Cardiac function: Left ventricular ejection fraction at least 45%
• Estimated creatinine clearance greater than 60 ml/min (C-G formula)
• Pulmonary function: DLCO (diffusing capacity of lung for carbon monoxide) corrected for hemoglobin at least 60% and FEV1 (forced expiratory volume at one second) predicted at least 60%
• Liver function: AST(Aspartate aminotransferase)/ALT(Alanine aminotransferase) \<3x Upper Limit of Normal (ULN); Total bilirubin \<2 mg/dL excluding Gilbert's syndrome or hemolysis
• Karnofsky Performance Score at least 70%.

You may not qualify if:

• Prior allogeneic transplant
• Active CNS (central nervous system) involvement by malignant cells
• Patients with secondary acute myeloid leukemia arising from myeloproliferative neoplasms or overlap syndromes, including CMML(chronic myelomonocytic leukemia) and MDS/MPN (myelodysplastic syndromes/myeloproliferative neoplasms) syndromes; patients with secondary acute myeloid leukemia arising from myelodysplastic neoplasm are eligible.
• Patients with uncontrolled bacterial, viral, or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment.
• Active or inadequately treated latent infection with Mycobacterium tuberculosis (i.e., TB).
• Patients seropositive for human immunodeficiency virus (HIV) with detectable viral load. HIV+ patients with an undetectable viral load on antiviral therapy are eligible.
• Evidence of uncontrolled hepatitis B virus (HBV) or hepatitis C virus (HCV). The study allows:
• Positive HBV serology with undetectable viral load and ongoing antiviral prophylaxis to prevent potential HBV reactivation.
• Positive HCV serology with quantitative PCR (polymerase chain reaction) for plasma HCV RNA below the lower limit of detection, with or without concurrent antiviral HCV treatment.
• Female patients who are pregnant or lactating
• Patients with a serious medical or psychiatric illness likely to interfere with participation in this clinical study
• Patients with prior malignancies except resected non-melanoma skin cancer or treated cervical carcinoma in situ. Cancer treated with curative intent ≥ 5 years previously will be allowed. Cancer treated with curative intent \< 5 years previously must be reviewed and approved by the Protocol Officer or Chairs, qualifying as below.
• the participant has been disease-free for at least 2 years and is deemed by the investigator to be at low risk of recurrence of that malignancy, or
• the cancer has been deemed indolent with no progression over the last 2 years, and deemed by the investigator to be at low risk for further progression during the course of study and follow-up
• the only prior malignancy was cervical cancer in situ and/or basal cell or squamous cell carcinoma of the skin

Sponsors & Collaborators

• Hannah Choe, MD: lead
• Incyte Corporation: collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Leukemia; Anemia, Refractory, with Excess of Blasts; Leukemia, Myelomonocytic, Chronic

Interventions

ruxolitinib; Hematopoietic Stem Cell Transplantation; Cyclophosphamide; Tacrolimus

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia, Refractory; Anemia; Myelodysplastic Syndromes; Bone Marrow Diseases; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Macrolides; Lactones

Study Officials

• Hannah Choe, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State University Comprehensive Cancer Center

CONTACT

1-800-293-5066; OSUCCCClinicaltrials@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 18, 2025
• First Posted: November 25, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: December 24, 2025

Record last verified: 2025-12

Locations

US (1)