A Phase 2 interventional study of Ruxolitinib and Myeloablative conditioning regimen in Leukemia, Myelodysplasia and Chronic Myelomonocytic Leukemia, sponsored by Hannah Choe, MD. Recruiting at 3 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-02.
Sponsored by Hannah Choe, MD · Phase 2, Interventional, and Treatment
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).
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.
Patients undergoing allogeneic hematopoietic cell transplantation for one of the following indications:
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).
Patients must have a related or unrelated peripheral blood stem cell donor as follows:
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
Allowed maintenance includes:
BCR/ABL inhibitors: imatinib, ponatinib, dasatinib, nilotinib
Exclusion Criteria:
Evidence of uncontrolled hepatitis B virus (HBV) or hepatitis C virus (HCV). The study allows:
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.
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
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
Taken PO
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.
Patients will undergo HCT
Also known as: HCT
Given IV
Given PO
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.
Time frame: At day 180 post-transplant
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.
Time frame: 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.
Time frame: At 6 months
Chronic GVHD requiring immunosuppression
Rate of chronic GVHD requiring immunosupression at 1 year
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 2 years post transplant
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Hannah Choe, MD