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

An Open Label, Non-Randomized, Multi-Center Pilot Dose-Expansion Study of Low Dose Post-Transplant Cyclophosphamide/Tacrolimus/Ruxolitinib for GVHD Prophylaxis in Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation

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).

Study Overview

• Status: Recruiting
• Conditions: Leukemia; Chronic Myelomonocytic Leukemia; Myelodysplasia
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Tacrolimus; Drug: Ruxolitinib; Drug: Myeloablative conditioning regimen; Procedure: Hematopoietic Stem Cell Transplantation

Detailed Description

Primary Objective:

To assess survival without severe Grade 3-4 acute GVHD at Day 180 post-transplant in patients treated with GVHD prophylaxis in myeloablative allogeneic hematopoietic stem cell transplantation for patients treated with low dose PTCy(Cyclophosphamide)/Tac(Tacrolimus)/Rux(Ruxolitinib).

Secondary Objectives:

To describe rates of Grade II-IV and Grades III-IV acute GVHD, chronic GVHD requiring immunosuppression, hematologic recovery (neutrophil and platelet), disease relapse or progression, rates of Grade 3+ toxicity, primary and secondary graft failure, and overall survival (OS) for patients treated with low dose PTCy/Tac/Rux.

• Study Type: Interventional
• Enrollment (Estimated): 124
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: The Ohio State University Comprehensive Cancer Center; Phone Number: 1-800-293-5066; Email: OSUCCCClinicaltrials@osumc.edu

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University Comprehensive Cancer Center
      • Contact: Hannah K Choe, MD; Email: Hannah.Choe@osumc.edu
      • Principal Investigator: Hannah K Choe, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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%.
• Female patients (unless postmenopausal for at least 1 year before the screening visit, or surgically sterilized), agree to practice two (2) effective methods of contraception at the same time, or agree to completely abstain from heterosexual intercourse, from the time of signing the informed consent through 12 months post-transplant.
• Male patients (even if surgically sterilized), of partners of women of childbearing potential must agree to one of the following: practice effective barrier contraception or abstain from heterosexual intercourse from the time of signing the informed consent through 12 months post-transplant.
• Plans for the use of targeted small molecule inhibitor post-transplant maintenance therapy must be disclosed upon enrollment. Planned use of investigational maintenance agents is not permitted. Planned hypomethylating agents as maintenance therapy is not permitted.

Allowed maintenance includes:

• FLT3 inhibitors: gilteritinib, sorafenib, midostaurin
• IDH inhibitors: enasidenib, ivosidenib

• BCR/ABL inhibitors: imatinib, ponatinib, dasatinib, nilotinib

  • Other targeted therapies may be discussed with protocol chairsVoluntary written consent obtained prior to the performance of any study-related procedure that is not a part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
  • There are no restrictions based on blood counts as this intervention is being used in combination with intensive chemotherapy with intent to myeloablate.

Exclusion Criteria:

• 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.
• Arterial or venous thrombosis including DVT (deep vein thrombois), PE (pulmonary embolism), stroke, and myocardial infarction within six (6) months prior to enrollment or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia. Catheter-associated DVT is not exclusionary.
• 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
• Planned use of ATG or alemtuzumab in conditioning regimen
• Planned use of prophylactic donor leukocyte infusions
• Prior use of ruxolitinib
• Prior use of immune checkpoint inhibitors (i.e., PD1, PDL1, CTLA4 modulators) within six (6) months prior to conditioning
• History of congenital Long QT syndrome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (Feasibility); 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: Cyclophosphamide; Given IV; Drug: Tacrolimus; Given PO; Drug: Ruxolitinib; Taken PO; Drug: Myeloablative conditioning regimen; 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.; Procedure: Hematopoietic Stem Cell Transplantation; Patients will undergo HCT; Other Names: HCT
Experimental: Cohort 2 (dose expansion); 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: Cyclophosphamide; Given IV; Drug: Tacrolimus; Given PO; Drug: Ruxolitinib; Taken PO; Drug: Myeloablative conditioning regimen; 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.; Procedure: Hematopoietic Stem Cell Transplantation; Patients will undergo HCT; Other Names: HCT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
GVHD, relapse free survival (GRFS)	GVHD-free, relapse-free survival as a time to event outcome is defined as Grade III-IV acute GVHD, chronic GVHD requiring systemic immune suppression, underlying disease relapse or progression, or death by any cause.	At 6 months and 1 year
Grade II-IV acute GVHD and Grade III-IV acute GVHD	Cumulative incidences of Grade II-IV and III-IV acute GVHD will be determined. Acute GVHD will be graded according to standard MAGIC criteria. The time of onset of acute Grades II-IV and III-IV acute GVHD will be recorded, as well as the maximum grade achieved. Within the participants experiencing Grade II-IV acute GVHD, the proportion of patients with visceral involvement (liver or gut) will be described. Cumulative incidences of Minnesota standard and high risk acute GVHD will also be determined.	At 6 months
Chronic GVHD requiring immunosuppression	Rate of chronic GVHD requiring immunosupression at 1 year	At 1 year
GVHD Free Survival (GFS)	Events for this time to event outcome is defined as any of the following: 1) Grade III-IV acute GVHD, 2) chronic GVHD requiring systemic immune suppression, or 3) death by any cause. The time to the event is defined as the time to the earliest of the qualifying events. Subjects alive without experiencing an event will be censored at last available GVHD assessment	At 1 year
Hematologic Recovery (Neutrophil Counts)	Hematologic recovery will be assessed according to neutrophil and platelet counts recovery after transplant. Neutrophil recovery is defined as achieving an absolute neutrophil count (ANC) greater than or equal to 500/mm3 for three consecutive measurements on three different days. The first of the three days will be designated the day of neutrophil recovery. The competing event is death or subsequent transplant without neutrophil recovery. For patients who never drop ANC below 500/mm3, the date of neutrophil recovery will be Day +1 post-transplant.	Up to 2 years post transplant
Disease Relapse or Progression	Number of patients with disease relapse or progression. Relapse is defined by either morphological or cytogenetic evidence of acute leukemia or MDS consistent with pre-transplant features. Relapse will be diagnosed when there is: Reappearance of leukemia blast cells in the peripheral blood; or,; Greater than 5% blasts in the bone marrow, not attributable to another cause (e.g., bone marrow regeneration); or, Page 56 of 63; The appearance of previous or new dysplastic changes (MDS specific) within the bone marrow with falling donor chimerism; or,; The development of extramedullary leukemia or leukemic cells in the cerebral spinal fluid or,; The reappearance of cytogenetic abnormalities present prior to transplantation	At 1 year
Non-relapse Mortality (NRM)	The cumulative incidence of NRM will be estimated after hematopoietic cell transplantation (HCT). An event for this endpoint is death without evidence of disease progression or recurrence. Disease progression or recurrence will be considered competing events.	At 1 year
Grade 3+ Toxicities	Adverse events and toxicities will be summarized using the NCI CTCAE v5.0. The person-year rates of Grade 3+ toxicity, grade 2-3 infections will be calculated with 95% CI.	Up to 2 years post transplant
Disease-Free Survival (DFS)	Disease-free survival is the time from date of transplant to death or relapse/progression, whichever comes first. The event for this endpoint is relapse/progression or death. Participants alive and disease free will be censored at last available disease assessment.	At 1 year
Overall Survival (OS)	Overall survival is defined as the time interval between date of transplant and death from any cause. The event for this endpoint is death from any cause. Surviving participants will be censored at last follow-up.	At 1 year and 2 years
Hematologic Recovery (Platelet Counts)	Platelet recovery is defined by two different metrics: the first day of a sustained platelet count greater than or equal to 20,000/mm3 or greater than or equal to 50,000/mm3 with no platelet transfusions in the preceding seven days. The first day of sustained platelet count above these thresholds will be designated the day of platelet engraftment. The competing event is death or subsequent transplant without platelet recovery. For patients who never drop their platelet count below 20,000/mm3 or 50,000/mm3, the date of platelet recovery will be Day +1 post HCT.	Up to 2 years post transplant

Collaborators and Investigators

• Sponsor: Hannah Choe, MD
• Collaborators: Incyte Corporation
• Investigators: Principal Investigator: Hannah Choe, MD, Ohio State University Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• The Jamesline

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: November 18, 2025
• First Submitted That Met QC Criteria: November 18, 2025
• First Posted (Estimated): November 25, 2025

Study Record Updates

• Last Update Posted (Actual): December 24, 2025
• Last Update Submitted That Met QC Criteria: December 23, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Anemia; Myelodysplastic Syndromes; Anemia, Refractory; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia; Leukemia, Myelomonocytic, Chronic; Anemia, Refractory, with Excess of Blasts; Organic Chemicals; Therapeutics; Surgical Procedures, Operative; Hydrocarbons; Transplantation; Macrolides; Lactones; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Stem Cell Transplantation; Cyclophosphamide; Tacrolimus; Hematopoietic Stem Cell Transplantation; ruxolitinib
• Other Study ID Numbers: OSU-24102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No