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OncoMatch/Clinical Trials/NCT04959175

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

Is NCT04959175 recruiting? Yes, currently enrolling (May 2026). This Phase 1/2 trial studies multiple treatments for hematologic neoplasms.

Phase 1/2RecruitingNational Cancer Institute (NCI)NCT04959175Data as of May 2026

Treatment: Mycophenolate Mofetil · Fludarabine · Sirolimus · Filgrastim · Cyclophosphamide · MesnaBackground: 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.

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Extracted eligibility criteria

Cancer type

Acute Myeloid Leukemia

Acute Lymphoblastic Leukemia

Non-Hodgkin Lymphoma

Multiple Myeloma

Myelodysplastic Syndrome

Chronic Lymphocytic Leukemia

Biomarker criteria

Allowed: TP53 17p deletion

Chronic lymphocytic leukemia with 17p deletion and/or unmutated IgHV

Prior therapy

Must have received: proteasome inhibitor

Multiple myeloma, stage III, relapsing after therapy with both a proteasome inhibitor and an immunomodulatory drug (IMiD)

Must have received: immunomodulatory drug

Multiple myeloma, stage III, relapsing after therapy with both a proteasome inhibitor and an immunomodulatory drug (IMiD)

Must have received: BTK inhibitor

Chronic lymphocytic leukemia...refractory or intolerant of both BTK and PI3K inhibitors

Must have received: PI3K inhibitor

Chronic lymphocytic leukemia...refractory or intolerant of both BTK and PI3K inhibitors

Must have received: tyrosine kinase inhibitor

Chronic myelogenous leukemia resistant to or intolerant of >=3 tyrosine kinase inhibitors

Cannot have received: investigational agent

Exception: Prior experimental therapies must have been completed at least 2 weeks prior to the date of beginning conditioning.

Subjects who are receiving any other investigational agents. Prior experimental therapies must have been completed at least 2 weeks prior to the date of beginning conditioning.

Lab requirements

Kidney function

Serum creatinine clearance of >=45 ml/minute calculated using the Cockcroft-Gault equation

Liver function

Total bilirubin <=2X the upper limit of normal; Alanine aminotransferase and aspartate aminotransferase <=5X the upper limit of normal.

Cardiac function

Cardiac ejection fraction >=35%

Adequate organ function defined as possessing all of the following: Cardiac ejection fraction >=35%; Forced expiratory volume-1, forced vital capacity, and diffusing capacity of the lung for carbon monoxide (corrected for hemoglobin) all of >=40% predicted; Serum creatinine clearance of >=45 ml/minute calculated using the Cockcroft-Gault equation; Total bilirubin <=2X the upper limit of normal; Alanine aminotransferase and aspartate aminotransferase <=5X the upper limit of normal.

Structured fields extracted by AI. May contain errors — verify against the official protocol.

US trial sites

  • National Institutes of Health Clinical Center · Bethesda, Maryland
  • Hospital of the University of Pennsylvania · Philadelphia, Pennsylvania

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