Low-dose Cyclophosphamide and Ruxolitinib for preventing Graft-versus-Host Disease

A Phase II Trial of De-escalated PTCy and Ruxolitinib for GVHD Prophylaxis in Patients Undergoing Reduced Intensity Conditioning Allogeneic HCT

This study is testing a new combination of low-dose medications to see if it can help older adults who are getting a stem cell transplant avoid developing graft-versus-host disease.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 56 (estimated)
• Ages: 60 Years and up
• Sex: All
• Sponsor: Medical College of Wisconsin (Academic / other)
• Drugs / interventions: Chimeric antigen receptor, fludarabine, ruxolitinib, cyclophosphamide
• Locations: 1 site (Milwaukee, Wisconsin)
• Trial ID: NCT05622318 on ClinicalTrials.gov

What this trial studies

This open-label phase 2 study investigates the safety and efficacy of a low-dose regimen of cyclophosphamide and ruxolitinib for preventing graft-versus-host disease (GVHD) in older adults undergoing allogeneic hematopoietic cell transplantation (HCT). Participants will receive a combination of cyclophosphamide, tacrolimus, mycophenolate mofetil, and ruxolitinib as part of their GVHD prophylaxis. The study aims to assess the outcomes of this de-escalated approach compared to standard prophylaxis methods. Patients will be monitored for GVHD incidence and overall safety throughout the study period.

Who should consider this trial

Good fit: Ideal candidates include older adults with a history of hematologic malignancy who are in remission and have a matched peripheral blood stem cell donor.

Not a fit: Patients with active hematologic malignancies or those without a suitable donor may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce the incidence of GVHD in patients undergoing HCT, improving their overall outcomes and quality of life.

How similar studies have performed: Other studies have explored similar prophylactic approaches, showing promise in reducing GVHD incidence, but this specific combination is novel.

Eligibility criteria

Inclusion Criteria:

1. History of hematologic malignancy.
2. Must be in remission:

   * Acute Leukemia, chronic leukemia, or myelodysplasia/myeloproliferative neoplasm (excluding primary myelofibrosis): No circulating blasts and \<5% blasts in the bone marrow.
   * Hodgkin and non-Hodgkin lymphomas: Chemo-sensitive disease at time of transplant
3. Patients must have a related or unrelated peripheral blood stem cell donor that is an 8/8 match at HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing. Unrelated donors must be willing to donate peripheral blood stem cells and meet NMDP criteria for donation.
4. Planned reduced intensity conditioning therapy with fludarabine/melphalan, with total dose of melphalan of 100-140 mg/m\^2 IV or fludarabine/busulfan with total dose of busulfan of 6.4 mg/kg IV.
5. Karnofsky Performance Scale of 60 or greater.
6. Male participants must agree to abstinence or to use of barrier contraception during the entire study period.
7. Female participants of childbearing potential will require a negative pregnancy test and should agree to practice two effective methods of contraception during the entire study period.
8. Ability to understand a written informed consent document, and the willingness to sign it.

Exclusion Criteria:

1. Prior allogeneic HCT or Chimeric antigen receptor (CAR) -T cell therapy.
2. Patients with liver dysfunction evidenced by bilirubin ≥2x upper limit normal (ULN), except for a history of Gilbert syndrome.
3. Patients with renal impairment defined by creatinine\<2mg/dL.
4. Patients with cardiac dysfunction defined by a left ventricular ejection fraction ≤45%.
5. Patients with pulmonary dysfunction defined by a forced expiratory volume in the first second (FEV1) or diffusing capacity for carbon monoxide (DLCO) (corrected for hemoglobin) ≤50% of predicted.
6. Patients with a chronic or active infection requiring systemic treatment during and after transplant.
7. Presence of other active malignant disease diagnosed within 12 months, except for adequately treated non-melanoma skin cancer, adequately treated melanoma grade 2 or less, or cervical intraepithelial neoplasia. Active malignancy is malignancy receiving treatment.
8. Pregnant or lactating subjects.

Where this trial is running

Milwaukee, Wisconsin

• Froedtert Hospital & the Medical College of Wisconsin — Milwaukee, Wisconsin, United States (Recruiting)

Study contacts

• Principal investigator: Sameem Abedin, MD — Medical College of Wisconsin
• Study coordinator: Medical College of Wisconsin Cancer Center Clinical Trials Office

Conditions Graft-versus-host Disease; Graft-versus-host disease; Ruxolitinib; Graft-versus-host disease prophylaxis