Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) With Low-Dose Post-Transplant Cyclophosphamide for Prophylaxis of Graft-versus-Host Disease in Hematological Malignancies
This Phase 2, single-arm, open-label study aims to evaluate the safety and efficacy of low-dose (25 mg/kg) post-transplant cyclophosphamide (PTCy) for prophylaxis of Graft-versus-Host Disease (GVHD) in patients undergoing allogeneic stem cell transplantation following reduced-intensity or non-myeloablative conditioning. The study will focus on matched sibling, matched unrelated, and haploidentical peripheral blood stem cell donors. The primary endpoint is 1-year GVHD-Free Relapse-Free Survival (GRFS). The study seeks to determine if low-dose PTCy offers similar outcomes as higher doses, with potentially reduced toxicity.
• Age 18 or older at the time of study enrollment.
• Patients with acute leukemia (acute myeloid leukemia, acute lymphoblastic leukemia, mixed phenotype acute leukemia) or chronic myeloid leukemia with no circulating blasts and less than 5% blasts in the bone marrow.
⁃ Flow cytometric, polymerase chain reaction (PCR) or next generation sequencing (NGS) detected measurable residual disease is permitted.
• Patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia with no circulating blasts and less than 10% blasts in the bone marrow (exception allowed due to lack of difference in outcomes with \<5% vs 5-10% blasts in this disease).
• Patients with secondary acute myeloid leukemia progressing from pre-existing myelodysplastic syndrome, myeloproliferative disease (MPN), or MDS/MPN overlap syndrome.
• Patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma who are indicated for allogeneic stem cell transplantation.
• Patients with lymphoma who are indicated for allogeneic stem cell transplantation, including follicular lymphoma, Hodgkin lymphoma, diffuse large B cell lymphoma (including primary mediastinal B cell lymphoma), mantle cell lymphoma, peripheral T cell lymphomas, and Richter's transformation.
• Planned reduced intensity or non-myeloablative conditioning regimen.
• Patients must have a related or unrelated peripheral blood stem cell donor as follows:
⁃ Sibling donor must be at least haploidentical using high resolution DNA-based HLA typing.
⁃ Children or parent donor must be at least haploidentical using high resolution DNA-based HLA typing. Children donors must be at least 18 years of age at the time of evaluation.
⁃ Unrelated donors must be a 7/8 or 8/8 match at HLA-A, B, C, and DRB1 at high resolution using DNA based typing.
• Cardiac function: must demonstrate at ejection fraction of at least 40%.
• Pulmonary function: must have FEV1 of at least 50% predicted, and DLCO corrected for hemoglobin of at least 40% predicted.
• Karnofsky performance status at least 70%.
• Women of childbearing potential (WOCP), defined as not surgically sterile (hysterectomy, tubal ligation, or oophorectomy) or at least 1 year postmenopausal, must have a negative serum pregnancy test before conditioning regimen.
• Female patients (unless post-menopausal or surgically sterilized) must agree to practice two effective methods of contraception simultaneously or agree to completely abstain from heterosexual intercourse from the time of signing informed consent through 12 months post-transplant.
• Male patients (even if surgically sterilized) who are partners of women of childbearing potential must agree to practice effective barrier contraception or abstain from heterosexual intercourse from the time of signing the informed consent through 12 months post-transplant.