Clinical trial NCT05622318: De-escalated Cyclophosphamide (PTCy) and Ruxolitinib for Graft-versus-Host Disease (GVHD) Prophylaxis
Official title: A Phase II Trial of De-escalated PTCy and Ruxolitinib for GVHD Prophylaxis in Patients Undergoing Reduced Intensity Conditioning Allogeneic HCT
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Graft-versus-host Disease
Keywords: Graft-versus-host disease
Ruxolitinib
Graft-versus-host disease prophylaxis
Lead sponsor: Medical College of Wisconsin
Sponsor class: OTHER
First posted: 2022-11-18
Enrollment: 56
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label phase 2 study designed to explore the efficacy and safety of low-dose PTCy-ruxolitinib GVHD prophylaxis in older adults undergoing allogeneic HCT with a matched sibling or unrelated donor with a peripheral blood stem cell graft.

Detailed description: Following reduced intensity conditioning and 8/8-matched peripheral blood transplant on Day 0, all patients will receive a GVHD prophylaxis post-transplant composed of the following: (i) cyclophosphamide administered at 25 mg/kg on Day +3 and +4, (ii) tacrolimus beginning on Day +5 and through Day +180 and administered with a trough target of 5-10 ng/ml through Day +90 and tapered thereafter; (iii) mycophenolate mofetil (MMF) administered at 15 mg/kg thrice daily beginning on Day +5 through Day +35; and (iv) ruxolitinib administered at 5 mg twice daily starting after engraftment (between Days +30 and +60) and continuing through one year post transplant.

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.

Primary outcomes:
measure: The number of subjects who experience GVHD-free survival.
timeFrame: One year (365 Days) after hematopoietic cell transplantation (HCT)
Secondary outcomes:
measure: The number of subjects with acute GVHD at Day +100.
timeFrame: Day +100 after HCT
measure: The number of subjects with acute GVHD at Day +180.
timeFrame: Day +180 after HCT
measure: The number of subjects with chronic GVHD at one year.
timeFrame: One year after HCT
measure: The number of subjects with non-relapse mortality at Day +100.
timeFrame: Day +100 after HCT
measure: The number of subjects with non-relapse mortality at one year.
timeFrame: One year after HCT
measure: Overall survival at one year.
timeFrame: One year after HCT
Other outcomes:
Locations:
city: Milwaukee
country: United States
facility: Froedtert Hospital & the Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Medical College of Wisconsin
name: Sameem Abedin, MD
role: PRINCIPAL_INVESTIGATOR
References: