Phase I/II Study to Reduce Cyclophosphamide Dosing for Bone Marrow Transplants
This study is for people aged 12 to 85 with certain blood cancers (hematologic malignancies) who are having a bone marrow transplant (Allogeneic HSCT). Researchers are testing if a lower dose of cyclophosphamide, a chemotherapy drug, can still prevent a serious complication called graft-versus-host disease (GVHD) while causing fewer side effects. GVHD happens when the donor cells attack your body. You will also receive other medications like Mycophenolate Mofetil, Fludarabine, Sirolimus, and Filgrastim. The main goal is to find the best dose of cyclophosphamide to prevent severe GVHD within 60 days after your transplant. The study is currently recruiting up to 320 participants.
- Study design
- This is an interventional study, meaning participants will receive specific treatments as part of the research. It aims to enroll 320 participants.
- What's involved
- Not specified in the trial record.
- Compensation
- Not stated in the trial record.
- Follow-up
- The primary outcome for this study is measured at 60 days after the transplant.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT04959175
Phase I/II Study to Reduce Post-transplantation Cyclophosphamide Dosing for Older or Unfit Patients Undergoing Bone Marrow Transplantation for Hematologic Malignancies
Recruiting
PHASE1Ages 12–85InterventionalTreatmentNational Cancer Institute (NCI)Government-funded
~320 participants
Updated 2026-06-11 on ClinicalTrials.gov
What's tested:Mycophenolate MofetilAllogeneic HSCTFludarabineSirolimusFilgrastimCyclophosphamide
At a glance
Recruiting sites
2 of 2 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
determine if optimal dose of PTCy to prevent grade III-IV acute GVHD (aGVHD) at day +60
Measured over 60 days
Conditions
Where it's being run
2 sites across 2 statesMaryland1
Pennsylvania1
Study leadership
- Christopher G Kanakry, M.D. · PRINCIPAL_INVESTIGATOR · National Cancer Institute (NCI)
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Acute myeloid leukemia in morphologic complete remission (\<5% blasts in the bone marrow, no detectable abnormal peripheral blasts, and no extramedullary disease)
B-cell acute lymphoblastic leukemia in first or subsequent complete remission
T-cell acute lymphoblastic leukemia in first or subsequent complete remission
Myelodysplastic syndrome of intermediate or higher score by the Revised International Prognostic Scoring System (IPSS-R)
Primary myelofibrosis of intermediate-2 or higher risk by the DIPSS
Chronic myelomonocytic leukemia
Chronic myelogenous leukemia resistant to or intolerant of \>=3 tyrosine kinase inhibitors or with history of accelerated phase or blast crisis
B-cell lymphoma including Hodgkin lymphoma that has relapsed within 1 year of completion of primary treatment, after autologous transplantation or has progressed through at least 2 lines of therapy
Chronic lymphocytic leukemia with 17p deletion and/or unmutated IgHV or refractory or intolerant of both BTK and PI3K inhibitors
Mature T or NK neoplasms as defined in the WHO guidelines of sufficient type and severity for allogeneic HCT based on the Prognostic Index for T-cell lymphoma (PIT) score of low-intermediate risk or higher60 or on recently published clinical practice guidelines
Hematologic malignancy of dendritic cell or histiocytic cell type
Multiple myeloma, stage III, relapsing after therapy with both a proteasome inhibitor and an immunomodulatory drug (IMiD) 2. Age 60-85 years, or age 18-60 years and unfit for myeloablative conditioning. Reasons for unfitness for myeloablative conditioning include:
Prior myeloablative HCT
Prior exposure to inotuzumab, gemtuzumab, or other agent that increases the risk for sinusoidal obstruction syndrome.
Significant organ dysfunction (e.g., creatinine or liver enzymes above the upper limit of normal or EGFR \<=70 ml/min/1.73sq.m; prior sinusoidal obstruction syndrome, hepatic fibrosis, hepatic steatosis, or nodular regenerative hyperplasia; reduced ejection fraction \<55% or focal hypokinesis, FEV1 or adjusted DLCO \<75% of predicted)
Hematopoietic Cell Transplantation- Comorbidity Index (HCT-CI) \>= 3
Subject refusal of MAC (including subjects insistent on trying to maintain fertility)
Pre-frail or frail by Fried s frailty phenotype
Karnofsky performance score \<80
Significant life-threatening toxicities associated with prior chemotherapy
Co-morbidity considered by the treating physician to be exclusionary of MAC 3. At least one potentially suitable HLA-matched related, HLA-haploidentical first degree or collateral related, HLA-matched unrelated, or \>=5/10 HLA-mismatched unrelated donor. 4. Karnofsky performance score \>=60 5. Ability of subject to understand and the willingness to sign a written informed consent document. 6. 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. 7. Nonmyeloablative conditioning is toxic to the developing human fetus and is teratogenic. For this reason, the following measures apply:
Women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for at least one year post-transplant.
Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
WOCBP must have a negative serum or urine pregnancy test within 7 days prior to enrollment. 8. For NIH treated subjects only: subjects requiring standard therapies to prepare for HCT should be referred in remission, if possible. However, these diseases are often aggressive and require swift evaluation for HCT while concurrently attempting to establish disease control through the administration of standard therapies. If ongoing therapy for the underlying disease outside of the NIH is not in the best interest of the subject according to the clinical judgment of the NIH PI, then the subject may receive standard treatment for his/her underlying hematologic malignancy as a bridge to HCT on this protocol, prior to starting the research phase of the study. If it becomes apparent that the subject will not be able to proceed to HCT, then he/she must come off study. Subjects receiving standard therapy will be told about the therapy, associated risks, potential benefits, alternatives to the proposed therapy, and the availability of receiving the same treatment elsewhere, outside of a research protocol.
Exclusion
Leukemia not having achieved morphologic remission (i.e. bone marrow blasts \>5% or active extramedullary disease)
Lymphoma not having achieved at least a partial response to prior chemotherapy or radiation 3. Uncontrolled intercurrent illness that in the opinion of the site PI would make it unsafe to proceed with transplantation. 4. The potential for some of the study medications to be transmissible via breast milk of nursing mothers is unknown. Because there is unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding must be discontinued. 5. Active malignancy of non-hematopoietic type which is: metastatic, relapsed/refractory to treatment, or locally advanced and not amenable to curative treatment, or limited disease treated with curative intent treatment within the last 2 years. This excludes nonmelanoma skin cancers.
What this trial measures
- determine if optimal dose of PTCy to prevent grade III-IV acute GVHD (aGVHD) at day +6060 days
The fraction of evaluable patients who experience grade III-IV aGVHD at day +60 will be determined and reported along with 80% and 95% two-sided confidence intervals. In addition, a cumulative incidence curve for this endpoint will be constructed.