Phase I/II Study to Reduce Post-transplantation Cyclophosphamide Dosing for Older or Unfit Patients Undergoing Bone Marrow Transplantation for Hematologic Malignancies

Part of paid clinical trials in Bethesda, Maryland.

Sponsor
National Cancer Institute (NCI)
Study ID
NCT04959175
Phase
PHASE1/PHASE2
Status
Recruiting
Apply to this trial

Conditions

  • Hematologic Neoplasms

Eligibility Criteria

Sex
ALL
Age
12 Years - 85 Years
Healthy Volunteers
Accepted

Interventions

  • Mycophenolate Mofetil — DRUG
    15 mg/kg orally or IV three times daily (max 1000 mg/dose) starting on day +5, continued through day +35. May be continued beyond the protocol specified stop date if there is GVHD or mixed chimerism.
  • Allogeneic HSCT — PROCEDURE
    Stem cell transplant
  • Fludarabine — DRUG
    30 mg/m2 IV infusion over 30-60 minutes once daily for 5 days (Pre-Transplant days -6 through -2).
  • Sirolimus — DRUG
    Loading dose of 6 mg orally given on day +5 (calculated based on actual body weight, max initial dose 6 mg), 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 +60 with no taper. May be continued beyond the protocol specified stop date if there is GVHD or mixed chimerism.
  • Filgrastim — DRUG
    begins on day +5 at a dose of 5 mcg/kg/day (actual body weight) IV or subcutaneously, until the absolute neutrophil count is \> 1,000/mm3 over the course of three days or \> 5,000/mm3 on one day. Rounding to the nearest vial is allowed. G-CSF may be stopped early or not administered if required by the clinical circumstance. Additional G-CSF may be administered as warranted.
  • Cyclophosphamide — DRUG
    Pre-transplant: 14.5 mg/kg/day IV daily for 2 days pre-transplant (Pre-Transplant days -6 and -5). Post-transplant: 25 mg/kg/day or 35 mg/kg/day (Post-transplant days +3 and +4).
  • Mesna — DRUG
    25 or 35 mg/kg (equal to the cyclophosphamide dose) as IV infusion concomitant with cyclophosphamide. Mesna may or may not be given with the pre-transplant cyclophosphamide depending on institutional practice.
  • Total Body Irradiation (TBI) — PROCEDURE
    400 centigray (cGy) to be delivered in 2 fractions as 200 cGy per fraction twice daily. Pre-Transplant Day -1 (or Day 0 prior to graft administration)

Study Details

Background: Certain blood cancers can be treated with blood or bone marrow transplants. Sometimes the donor cells attack the recipient's body, called graft-versus-host disease (GVHD). The chemotherapy drug cyclophosphamide helps reduce the risk and severity of GVHD. Researchers want to learn if using a lower dose of cyclophosphamide may reduce the drug's side effects while maintaining its effectiveness. Such an approach is being used in an ongoing clinical study at the NIH with promising results, but this approach has not been tested for transplants using lower doses of chemotherapy/radiation prior to the transplant. Objective: To learn if using a lower dose of cyclophosphamide will help people have a successful transplant and have fewer problems and side effects. Eligibility: Adults ages 18-85 who have a blood cancer that did not respond well to standard treatments or is at high risk for relapse without transplant, and their donors. Design: Participants may be screened with the following: Medical history Physical exam Blood and urine tests Heart and lung tests Body imaging scans (they may get a contrast agent) Spinal tap Bone marrow biopsy Participants will be hospitalized for 4-6 weeks. They will have a central venous catheter placed in a chest or neck vein. It will be used to give medicines, transfusions, and the donor cells, and to take blood. In the week before transplant, they will get 2 chemotherapy drugs and radiation. After the transplant, they will get the study drug for 2 days. They will take other drugs for up to 2 months. Participants must stay near NIH for 3 months after discharge for weekly study visits. Then they will have visits every 3-12 months until 5 years after transplant. Participants and donors will give blood, bone marrow, saliva, cheek swab, urine, and stool samples for research.

Key Dates

Start date
Sep 23, 2021
Status verified
Jun 2026
Primary completion
Apr 27, 2027
Completion
Apr 30, 2027

Study Design

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

Arms

  • No Intervention: Donors
    Collection of research samples on bone marrow donors
  • Experimental: Older, HLA-matched
    Subjects age 60-85 with hematologic malignancies and an HLA-matched related or unrelated donor
  • Experimental: Older, HLA-mismatched
    Subjects age 60-85 with hematologic malignancies and an HLA-haploidentical or HLA-mismatched unrelated donor
  • Experimental: Younger, HLA-matched
    Subjects age 18-60 unfit for MAC with hematologic malignancies and an HLA-matched related or unrelated donor
  • Experimental: Younger, HLA-mismatched
    Subjects age 18-60 unfit for MAC with hematologic malignancies and an HLA-haploidentical or HLA-mismatched unrelated donor

Primary Outcome Measure

determine if optimal dose of PTCy to prevent grade III-IV acute GVHD (aGVHD) at day +60 [ Time Frame: 60 days ]

Central Contacts

Locations (2)

FacilityCityStateZIPSite coordinators
National Institutes of Health Clinical CenterBethesdaMaryland20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)
[email protected]
800-411-1222
Hospital of the University of PennsylvaniaPhiladelphiaPennsylvania19104
Shannon McCurdy
[email protected]
215-614-0698

Find similar trials in Bethesda, MD

By research site
National Institutes of Health Clinical Center· Bethesda, MDHospital of the University of Pennsylvania· Philadelphia, PA

Related Studies