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Updated May 2026 · ClinicalTrials.gov

RECRUITINGPhase 1 / Phase 2INTERVENTIONAL

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

Phase I/II Study to Reduce Post-transplantation Cyclophosphamide Dosing for Older or Unfit Patients Undergoing Bone Marrow Transplantation for Hematologic Malignancies (NCT04959175) is a Phase 1 / Phase 2 interventional studying Hematologic Neoplasms, sponsored by National Cancer Institute (NCI). RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

What Stage of Research Is This?

Phase 1 trials test a new treatment for the first time in humans, focusing on safety, dosing, and how the body processes the drug. For Hematologic Neoplasms, a Phase 1 study typically enrolls a small number of participants — often healthy volunteers or patients who have exhausted standard treatment options. Phase 1 results determine whether a treatment moves into larger Phase 2 efficacy studies.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

A target enrollment of 320 participants makes this a sizable late-stage trial. Studies in this range typically have enough power to detect clinically meaningful differences from a comparator and to characterize less-common side effects.

Who May Be Eligible (Plain English)

-INCLUSION CRITERIA - Recipient 1. Subjects must have a diagnosed by tissue sample (biopsy-confirmed) hematologic malignancy with standard indication for allogeneic hematopoietic cell transplantation including, but not limited to, one of the following: - 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 ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
-INCLUSION CRITERIA - Recipient 1. Subjects must have a histologically or cytologically confirmed hematologic malignancy with standard indication for allogeneic hematopoietic cell transplantation including, but not limited to, one of the following: * 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 CRITERIA - Recipient: 1. 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. 2. Poorly controlled malignant indication for transplantation such as: * 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. INCLUSION CRITERIA - Donor: Related (age \>=12) and unrelated (age \>=18) donors deemed eligible (i.e., evaluated at NIH in accordance with existing institutional Standard Policies and Procedures or evaluated per the standards required by the IRB of the National Marrow Donor Program or applicable registry), and willing to donate research samples will be included. EXCLUSION CRITERIA - Donor: None

Treatments Being Tested

DRUG

Mycophenolate Mofetil

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.

PROCEDURE

Allogeneic HSCT

Stem cell transplant

DRUG

Fludarabine

30 mg/m2 IV infusion over 30-60 minutes once daily for 5 days (Pre-Transplant days -6 through -2).

DRUG

Sirolimus

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.

DRUG

Filgrastim

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.

DRUG

Cyclophosphamide

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).

DRUG

Mesna

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.

PROCEDURE

Total Body Irradiation (TBI)

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)

Locations (2)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

National Institutes of Health Clinical Center
Bethesda, Maryland, United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT04959175), the sponsor (National Cancer Institute (NCI)), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT04959175 clinical trial studying?

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… The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT04959175?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT04959175?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT04959175. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT04959175. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.