De-escalated Cyclophosphamide (PTCy) and Ruxolitinib for Graft-versus-Host Disease (GVHD) Prophylaxis

NCT05622318 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PRO00046962
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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.

Conditions

Graft-versus-host Disease

Keywords

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

Outcome Measures

Primary Outcomes (1)

• The number of subjects who experience GVHD-free survival.

  This measure is defined as being alive without having experienced grade III/IV acute GVHD, or chronic GVHD requiring systemic immune suppression.

  One year (365 Days) after hematopoietic cell transplantation (HCT)

Secondary Outcomes (6)

• The number of subjects with acute GVHD at Day +100.

  Day +100 after HCT

• The number of subjects with acute GVHD at Day +180.

  Day +180 after HCT

• The number of subjects with chronic GVHD at one year.

  One year after HCT

• The number of subjects with non-relapse mortality at Day +100.

  Day +100 after HCT

• The number of subjects with non-relapse mortality at one year.

  One year after HCT

Study Arms (1)

Graft-versus-host disease prophylaxis

EXPERIMENTAL

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.

Drug: Cyclophosphamide; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Drug: Ruxolitinib

Interventions

Tacrolimus DRUG

Target level 5-10 ng/mL (If the subject experiences nausea and vomiting that prevents the oral intake of tacrolimus anytime during treatment, tacrolimus is to be given by IV at the appropriate dose that was used to obtain the therapeutic level \[IV:PO ratio = 1:4\]). Administered Days +5 through +90. Taper after Day +90 and discontinue on Day +180.

Also known as: Astagraf XL, Envarsus XR, Prograf

Graft-versus-host disease prophylaxis

Ruxolitinib DRUG

5 mg tablet twice daily after engraftment through Day +365. Taper after Day +365.

Also known as: INC424, Jakafi

Graft-versus-host disease prophylaxis

Cyclophosphamide DRUG

25 mg/kg by IV on Days +3 and +4.

Also known as: Cytoxan

Graft-versus-host disease prophylaxis

Mycophenolate Mofetil DRUG

15 mg/kg tablet thrice daily Days +5 through +35 every eight hours.

Also known as: CellCept

Graft-versus-host disease prophylaxis

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• History of hematologic malignancy.
• 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
• 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.
• 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.
• Karnofsky Performance Scale of 60 or greater.
• Male participants must agree to abstinence or to use of barrier contraception during the entire study period.
• 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.
• Ability to understand a written informed consent document, and the willingness to sign it.

You may not qualify if:

• Prior allogeneic HCT or Chimeric antigen receptor (CAR) -T cell therapy.
• Patients with liver dysfunction evidenced by bilirubin ≥2x upper limit normal (ULN), except for a history of Gilbert syndrome.
• Patients with renal impairment defined by creatinine\<2mg/dL.
• Patients with cardiac dysfunction defined by a left ventricular ejection fraction ≤45%.
• 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.
• Patients with a chronic or active infection requiring systemic treatment during and after transplant.
• 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.
• Pregnant or lactating subjects.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Cyclophosphamide; Tacrolimus; Mycophenolic Acid; ruxolitinib

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• Sameem Abedin, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 11, 2022
• First Posted: November 18, 2022
• Study Start: August 29, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: March 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)