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Protocol Details

Phase I/II Trial to Determine 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

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 12 Years
Max Age: N/A

Referral Letter Required


Population Exclusion(s)

Pregnant Women;


Reduced Intensity Conditioning;
Systemic Immunosuppressive Therapy;
Hematologic Malignancy;
Acute Myeloid Leukemia;
Calcineurin Inhibitor

Recruitment Keyword(s)



Peripheral Blood Stem Cell Transplantation;
Hematopoietic Stem Cell Transplantation

Investigational Drug(s)


Investigational Device(s)



Drug: Melphalan
Drug: Sirolimus
Radiation: Total Body Irradiation (TBI)
Drug: Cyclophosphamide
Drug: Mycophenolate Mofeti
Drug: Fludarabine
Procedure/Surgery: Allogeneic HSCT
Drug: Mesna
Drug: Filgrastim

Supporting Site

National Cancer Institute


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.


To find out if a lower dose of PTCy is more helpful for people who undergo blood stem cell transplants.


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.


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.

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-Participants must have a histologically or cytologically confirmed hematologic malignancy with standard indication for allogeneic hematopoietic cell transplantation limited to one of the following:

--Acute myeloid leukemia (AML) of intermediate or adverse risk disease by the 2017 European LeukemiaNet criteria in first morphologic complete remission (<5% blasts in the bone marrow, no detectable abnormal peripheral blasts, and no extramedullary disease)

--AML of any risk in second or subsequent morphologic complete remission

--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, relapsed 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 to 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 higher 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)

-Age >= 50 years or age 18-49 years and also meeting one of the following criteria:

--Prior myeloablative HCT

--Prior exposure to inotuzumab, gemtuzumab, or other agent that increases the risk for sinusoidal obstruction syndrome.

--Hematopoietic Cell Transplantation- Comorbidity Index (HCT-CI) >= 3

--Karnofsky performance score <80

--Co-morbidity considered by the treating physician to be exclusionary of myeloablative conditioning

-At least one potentially suitable HLA-haploidentical or 10/10 (HLA-A, B, C, DR, DQ) related or unrelated donor for HCT

-Karnofsky performance score >= 70

-Adequate organ function defined as possessing all of the following:

--Cardiac ejection fraction >= 45% by 2D ECHO;

--Forced expiratory volume-1 (FEV-1), forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) all of >= 50% predicted;

--Estimated serum creatinine clearance of >= 60 ml/minute/1.73m^2 calculated using eGFR in the clinical lab;

--Total bilirubin <= 2X the upper limit of normal;

--Alanine aminotransferase and aspartate aminotransferase <= 3X the upper limit of normal.

-Women of child-bearing potential (WOCBP) and men must agree to use highly effective contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for at least one year post-transplant.

-WOCBP must have a negative serum or urine pregnancy test within 7 days prior to initiation of conditioning regimen.

-Ability of participant to understand and the willingness to sign a written informed consent document.


-Related donor (age >=12) deemed suitable and eligible, and willing to donate, per clinical evaluations, who are additionally willing to donate blood, saliva, oral swab, and stool for research. Related donors will be evaluated in accordance with existing institutional Standard Policies and Procedures for determination of eligibility and suitability for clinical donation.

-Ability of participant or parent/legal guardian to understand and the willingness to sign a written informed consent document.



-Participants 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.

-Active breastfeeding.

-Active malignancy of non-hematopoietic type (excluding non-melanoma skin cancers) which is: metastatic, or 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 non-melanoma skin cancers.

-History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents.

-Uncontrolled intercurrent illness (e.g., severe endocrinopathy, disseminated intravascular coagulation, profound electrolyte disturbance, active infectious hepatitis, uncontrolled dental infection) that in the opinion of the Site PI would make it unsafe to proceed with transplantation.



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Not Provided

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Principal Investigator

Referral Contact

For more information:

Christopher G. Kanakry, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CRC BG RM 4-3142
(240) 760-6171

Amy H. Chai
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 4-3152
10 Center Drive
Bethesda, Maryland 20892
(301) 219-7105

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office

Clinical Trials Number:


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