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Fludarabine and Intermediate-dose Total Body Irradiation Conditioning plus Post-Transplant Cyclophosphamide for the Treatment of Patients Undergoing Allogeneic Stem Cell Transplant for Hematologic Cancers
Trial Status: active
This phase II trial tests how well a fludarabine and intermediate-dose total body irradiation (TBI) conditioning regimen plus graft versus host disease prophylaxis with cyclophosphamide, tacrolimus, and mycophenolate mofetil works in treating patients undergoing an allogeneic stem cell transplant for a hematologic (blood) cancer. A conditioning regimen is a treatment that uses a combination of chemotherapy and sometimes radiation to destroy cancer cells and help donor cells start to grow in the bone marrow. Fludarabine works by stopping the production of deoxyribonucleic acid (DNA) in cancer cells, which kills the cancer cells. TBI is a type of radiation where radiation is given in a way to cover all parts of the body to help kill the cancer cells and suppress the immune system, so the body does not attack the donor blood cells. Intermediate-dose TBI may achieve the same effect as higher doses of radiation therapy while lowering the risk of side effects. Graft versus host disease is a common development after allogeneic stem cell transplant. It happens when the donor cells attack and damage healthy tissues after transplant. For this reason, a treatment regimen called a graft versus host disease prophylaxis regimen is given after transplant. Cyclophosphamide works by cross-linking strands of DNA in cancer cells, which kills the cancer cells. Tacrolimus and mycophenolate mofetil are drugs that suppress the immune system. Fludarabine plus intermediate-dose TBI conditioning and a cyclophosphamide-containing prophylaxis regimen may be safe and effective in treating patients undergoing an allogeneic stem cell transplant for a hematologic cancer.
Inclusion Criteria
Patients ages 18-65 years
Patients with a diagnosis of one of the following hematologic malignancies:
* Acute myeloid leukemia or chronic myeloid leukemia with no circulating blasts and less than 5% blasts in the bone marrow;
* Myelodysplastic syndrome with less than 5% blasts in the bone marrow by immunohistochemistry (IHC) or flow cytometry whichever is highest;
* Myeloproliferative neoplasms with less than 5% blast in the marrow and peripheral blood;
* Acute lymphoblastic leukemia in complete response (CR) (Center for International Blood and Marrow Transplant Research [CIBMTR] criteria); or
* Lymphoma in CR (CIBMTR criteria)
Patients who are eligible for allogeneic stem cell transplant per Transplant Program standard operating procedures (SOPs)
Patients with a Karnofsky performance status (KPS) of >= 60%
Left ventricular ejection fraction (LVEF) >= 50%
Diffusion capacity of the lung for carbon monoxide (DLCO) >= 50% of predicted
Bilirubin =< 1.5 x upper limit of normal (ULN)
Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 2.5 x ULN
Creatinine clearance >= 50 mL/min
All participants of reproductive potential must use effective contraception following allogeneic hematopoietic stem cell transplantation (allo-HSCT), in accordance with guidelines from the American Society for Transplantation and Cellular Therapy (ASTCT), the Food and Drug Administration (FDA), and other expert bodies
For male participants:
* Male participants must use effective contraception for at least 12 months after transplant, and longer if receiving immunosuppressive or cytotoxic medications. Chemotherapy and radiation can cause DNA damage to sperm, and even if fertility returns, mutations may persist for months. In cases where drugs such as mycophenolate mofetil (MMF) or lenalidomide are used, FDA guidance requires contraception for at least 90 days after discontinuation. Sperm cryopreservation should be offered prior to conditioning. Participants must avoid fathering a child during this time frame
For female participants:
* Female participants of childbearing potential are required to use highly effective contraception for a minimum of 12 to 24 months post-transplant, or longer if still receiving immunosuppressive or teratogenic therapy. For drugs such as MMF, sirolimus, or ruxolitinib, contraception must continue for 3 months after the last dose
* A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (>= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements
Patients with a suitable donor for allogeneic stem cell transplant defined by:
* Matched sibling donors willing to donate mobilized peripheral blood (PBSC) or bone marrow (BM), meeting all institutional criteria for donation;
* Unrelated donors at > 7/8 (i.e., mismatched at only one of the HLA-A, HLA-B, HLA-C, and HLA-DRB1 loci) willing to donate mobilized PBSC or BM, and medically eligible to donate cells according to National Marrow Donor Program criteria; or
* Related haploidentical donors willing to donate PBSC or BM and meeting criteria for donation
Patients who are able to comply with follow-up visits and treatment plans
Patients who are able to give informed consent
Exclusion Criteria
Hematopoietic cell transplantation comorbidity index above 3
Patients with a Karnofsky performance status (KPS) of < 60%
Patients with active infections or other contraindications for allogeneic stem cell transplant
Patients who are unable or unwilling to give informed consent
Patients who have received a prior allogeneic transplant
Patients who are unable to comply with follow-up visits and treatment plans
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07214688.
I. To evaluate the efficacy of fludarabine plus intermediate-dose total body irradiation (TBI 800 cGy) with post-transplant cyclophosphamide (PTCy) to improve the 1-year survival of allogeneic stem cell transplant recipients.
SECONDARY OBJECTIVES:
I. To assess transplant-related mortality (TRM) at one year in allogeneic stem cell transplant recipients.
II. To evaluate the incidence of grade III-IV acute graft versus host disease (GVHD) in allogeneic stem cell transplant recipients.
III. To evaluate the incidence of chronic GVHD at one year in allogeneic stem cell transplant recipients.
IV. To assess GVHD-free, relapse-free survival (GRFS) at one year in allogeneic stem cell transplant recipients.
V. To assess disease status in allogeneic stem cell transplant recipients.
VI. To assess the relapse rate at one year in allogeneic stem cell transplant recipients.
OUTLINE:
Patients receive fludarabine intravenously (IV) once daily (QD) on days -6 to -2, undergo total body irradiation (TBI) for 2 fractions per day on days -2 and -1, and undergo peripheral blood stem cell (PBSC) or bone marrow (BM) transplantation on day 0. Patients then receive cyclophosphamide IV on days +3 and +4, tacrolimus orally (PO) starting on day +5 and continuing up to 12 months, and mycophenolate mofetil (MMF) PO three times daily (TID) on days +5 to +35. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) at screening and undergo positron emission tomography (PET)/computed tomography (CT) and/or collection of bone marrow and/or blood samples throughout the trial.
After completion of study treatment, patients are followed up at day +100 and months 6 and 12.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationHackensack University Medical Center
