Ruxolitinib to prevent graft-versus-host disease after allogeneic stem cell transplant

Randomized Pilot Study of Ruxolitinib for Switch-Maintenance Prophylaxis of Graft-versus-Host Disease in Allogeneic Hematopoietic Cell Transplantation After Intermediate-Dose Post-Transplant Cyclophosphamide (Rux Switch-Maintenance in Intermediate PTCY: RuSMa-PTCY) in Comparison to Full-Dose PTCY

This trial will test whether adding ruxolitinib to standard drugs better prevents chronic graft-versus-host disease in adults receiving an allogeneic stem cell transplant for blood cancers.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Memorial Sloan Kettering Cancer Center (Academic / other)
• Drugs / interventions: ruxolitinib
• Locations: 7 sites (Basking Ridge, New Jersey and 6 other locations)
• Trial ID: NCT07359859 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional trial compares two different GVHD prophylaxis regimens in adults undergoing allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Participants will receive one of two prophylaxis approaches that include combinations of post-transplant cyclophosphamide, tacrolimus, mycophenolate mofetil, and ruxolitinib. The primary outcome is the incidence of chronic GVHD up to one year after transplant, with safety and transplant-related outcomes also monitored. The trial is conducted at Memorial Sloan Kettering Cancer Center locations in New Jersey.

Who should consider this trial

Good fit: Adults (≥18) with a hematologic malignancy in morphologic remission who are planning an allogeneic stem cell transplant from a 7-8/8 HLA-matched related or unrelated donor or a related haploidentical donor, with Karnofsky score ≥70% and appropriate reproductive safety measures, are eligible.

Not a fit: Patients with active uncontrolled malignancy, poor performance status, incompatible donors, or contraindications to the study drugs or required contraception are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could reduce the incidence and long-term complications of chronic GVHD for transplant recipients.

How similar studies have performed: Ruxolitinib is approved for treating steroid-refractory GVHD and smaller studies have suggested it may help prevent GVHD, but prophylactic use after allo-HCT remains under investigation.

Eligibility criteria

Inclusion Criteria:

* Patients ≥18- years-old at time of consent
* Diagnosis: hematologic malignancy in morphologic remission (blasts \<5%, no evidence of extramedullary disease in AML or MDS). Patients with CR with incomplete count recovery (CRp or CRi) or minimal residual disease are allowed. Patients with lymphoma must have a complete or partial response
* Donor: related or unrelated 7-8/8 HLA-matched or related haploidentical
* Karnofsky score ≥ 70%
* Female subjects of childbearing potential (\<50 years old) have a negative serum or urine pregnancy test. Females of childbearing potential are defined as females without prior hysterectomy or who have had any evidence of menses in the past 12 months.

  °Sexually active females of childbearing potential enrolled in the study must agree to consistently use two forms of accepted methods of contraception during the course of the study and for 3 months after their last dose of the study drug. Effective birth control includes: \*Intrauterine device (IUD) plus one barrier method \*Stable doses of hormonal contraception for at least 3 months (e.g., oral, injectable, implant, transdermal) plus one barrier method \*2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gel that contain a chemical to kill sperm); or \* A vasectomized partner.
* For male subjects who are sexually active and who are partners of females of childbearing potential: Agreement to use two forms of contraception as per above and to not donate sperm during the treatment period and for at least 3 months after the last dose of study drug

Exclusion Criteria:

* Recipient of CD34+ selected or engineered stem cell graft
* Treatment with in vivo T cell depletion (e.g. anti-thymocyte globulin)
* Severely impaired renal function defined by serum creatinine \> 2mg/dL, renal dialysis requirement.
* Use of investigational agent within 14 days pre-HCT
* Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months
* Uncontrolled psychiatric illness
* Female patient who is pregnant or breastfeeding
* Known allergy or sensitivity to ruxolitinib

Where this trial is running

Basking Ridge, New Jersey and 6 other locations

• Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities) — Basking Ridge, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Monmouth (Limited Protocol Activities) — Middletown, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Bergen (Limited Protocol Activities) — Montvale, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activities) — Commack, New York, United States (Recruiting)
• Memorial Sloan Kettering Westchester (Limited Protocol Activities) — Harrison, New York, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York, New York, United States (Recruiting)
• Memorial Sloan Kettering Nassau (Limited Protocol Activites) — Rockville Centre, New York, United States (Recruiting)

Study contacts

• Principal investigator: Doris Ponce, MD, MS — Memorial Sloan Kettering Cancer Center
• Study coordinator: Doris Ponce, MD, MS

Conditions Hematologic Malignancies; graft-versus-host disease; allogeneic hematopoietic stem cell transplant