The Lowest Effective Dose of Post-Transplantation Cyclophosphamide in Combination With Sirolimus and Mycophenolate Mofetil as Graft-Versus-Host Disease Prophylaxis After Reduced Intensity Conditioning and Peripheral Blood Stem Cell Transplantation

Part of paid clinical trials in Duarte, California.

Sponsor
National Cancer Institute (NCI)
Study ID
NCT05436418
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

  • Hematopoietic Stem Cell Transplantation
  • Peripheral Blood Stem Cell Transplantation

Eligibility Criteria

Sex
ALL
Age
12 Years - 120 Years
Healthy Volunteers
Accepted

Interventions

  • Melphalan — DRUG
    Matched HCT: 100 mg/m\^2 IV on day -2 over 30 minutes. Haplo HCT: 100 mg/m\^2 IV on day -6 over approximately 20-30 minutes.
  • Sirolimus — DRUG
    Sirolimus: Loading dose of 6 mg orally given on day +5 (calculated based on actual body weight, max initial dose 6 mg)\^d, then maintenance dose starting at 2 mg orally daily on day +6 with dose adjustments to maintain a trough of 5-12 ng/ml, continued through day +80 with no taper. Doses should be modified as appropriate for drug interactions and may be modified based on institutional practice.
  • Total Body Irradiation (TBI) — RADIATION
    Haplo HCT only: A dose of 200 cGy will be administered on day -1.
  • Cyclophosphamide — DRUG
    based on dose level being tested (50, 35, 25, or 15 mg/kg) IV once daily over 2 hours on days +3 and +4. Cyclophosphamide will be dosed according to ideal body weight. Cyclophosphamide infusion on days +3 should be started between 70-74 hours after the start of the PBSC infusion. Cyclophosphamide infusion on day +4 should be started between 94-98 hours after the start of the bone marrow infusion.
  • Mycophenolate Mofeti — DRUG
    15 mg/kg orally or IV three times daily (max 1000 mg/dose) starting on day +5, continued through day +35. Dosing will be according to actual body weight.
  • Fludarabine — DRUG
    Matched HCT: 25 mg/m\^2/day infused IV over 60 minutes from day -7 to day -3. Haplo HCT: 40 mg/m\^2/day infused IV over approximately 30-60 minutes from day -5 to day -2
  • Allogeneic HSCT — PROCEDURE
    Stem cell transplant
  • Mesna — DRUG
    equal to the cyclophosphamide dose (50, 35, 25, or 15 mg/kg) as IV infusion concomitant with cyclophosphamide. Mesna is dosed in the same way as cyclophosphamide regarding ideal vs. actual body weight.b Dosing may be modified based on institutional standard practice.
  • Filgrastim — DRUG
    begins on day +5 at a dose of 5 mcg/kg/day (actual body weight; dose rounding is permitted e.g., nearest vial or syringe size) and is administered daily subcutaneously or IV until the absolute neutrophil count is \> 1000 cells/mm3 for three days or \> 5000 for one day.

Study Details

Background: Blood cancers (such as leukemias or lymphomas) often do not respond to standard treatments. A transplant of blood stem cells from a healthy donor can help people with these cancers. Sometimes these transplants cause serious side effects, including a common immunologic problem called graft-versus-host disease. A drug called cyclophosphamide given early after the transplant (post-transplantation cyclophosphamide, PTCy) can reduce these complications. But sometimes this drug has its own negative effects. Furthermore, studies in mice suggest that an intermediate, rather than very high, dose of this drug may best protect against graft-versus-host disease. Objective: To find out if a lower dose of PTCy is more helpful for people who undergo blood stem cell transplants. Eligibility: People aged 18 and older who have a blood cancer and are eligible for a transplant of blood stem cells from another person. Healthy donors are also needed but must be related to the individual needing the transplant. Design: Participants will undergo screening. Transplant recipients will have imaging scans and tests of their heart and lung function. They will be assessed for the status of their cancer, including bone marrow taken from their pelvis and possibly also scans and/or fluid drawn from the spine depending on the disease type. Donors will be screened for general health. They will give several tubes of blood. They will give an oral swab and saliva and stool samples for research. Recipients will be in the hospital at least 4 to 6 weeks. They will have a temporary catheter inserted into a vein in the chest or neck. Medications will be given and blood will be drawn through the catheter. The transplanted stem cells will be given through the catheter. Participants will receive medications both before and after the transplant. Participants will return to the clinic at least once a week for 3 months after leaving the hospital. Follow-up visits will continue periodically for 5 years.

Key Dates

Start date
Nov 18, 2022
Status verified
Jun 2026
Primary completion
Jun 25, 2027
Completion
Jun 25, 2028

Study Design

Enrollment
260 participants (estimated)
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • No Intervention: Donors (Haplo HCT)
    Research on collected samples
  • No Intervention: Donors (Matched HCT)
    Research on collected samples
  • Experimental: Phase I Dose De-escalation (Haplo HCT)
    PTCy at de-escalating doses to assess for safety and determine Phase II dose
  • Experimental: Phase I Dose De-escalation (Matched HCT)
    PTCy at de-escalating doses to assess for safety and determine Phase II dose
  • Experimental: Phase I Pilot for Comparative Data (Haplo HCT)
    Standard PTCy 50 mg/kgday on days +3 and +4
  • Experimental: Phase I Pilot for Comparative Data (Matched HCT)
    Standard PTCy 50 mg/kg/day on days +3 and +4
  • Experimental: Phase II Efficacy (Haplo HCT)
    PTCy at shortest duration, safe dose (from Phase I)
  • Experimental: Phase II Efficacy (Matched HCT)
    PTCy at shortest duration, safe dose (from Phase I)

Primary Outcome Measure

Phase II: Evaluate the efficacy of PTCy, at the lowest dose determined for each HLA-matching arm from phase I, as assessed by 1-year GVHD-free relapse-free survival (GRFS) rate. [ Time Frame: 1 year ]

Central Contacts

Locations (2)

FacilityCityStateZIPSite coordinators
City of HopeDuarteCalifornia91010
Ryotaro Nakamura, M.D.
[email protected]
626-218-2405
National Institutes of Health Clinical CenterBethesdaMaryland20892
For more information at the NIH Clinical Center contact National Cancer Institute Referral Office
888-624-1937

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By research site
City of Hope· Duarte, CANational Institutes of Health Clinical Center· Bethesda, MD

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