Chemotherapy, Total Body Irradiation, and Post-Transplant Cyclophosphamide in Reducing Rates of Graft Versus Host Disease in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant

• Status: Recruiting
• Trial end date: 2023-08-09
• Target enrollment: 0
• Participant gender: All

Summary

This phase II trial studies how well chemotherapy, total body irradiation, and post-transplant cyclophosphamide work in reducing rates of graft versus host disease in patients with hematologic malignancies undergoing a donor stem cell transplant. Drugs used in the chemotherapy, such as fludarabine phosphate and melphalan hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft versus host disease). Giving cyclophosphamide after the transplant may stop this from happening.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Roswell Park Cancer Institute
• Collaborator: National Cancer Institute (NCI)
• Treatments: Cyclophosphamide; Fludarabine; Fludarabine phosphate; Melphalan; Mycophenolic Acid; Sirolimus; Tacrolimus; Vidarabine

Criteria

Inclusion Criteria:

• The patient must have a diagnosis of one of the following (one must be yes):

• Acute myeloid leukemia (AML)

• Acute lymphoblastic leukemia (ALL)

• Chronic myelogenous leukemia (CML) (chronic phase intolerant or unresponsive to tyrosine kinase inhibitors, accelerated phase, history of blast crisis)

• Myelodysplastic syndrome (MDS)

• Myeloproliferative neoplasm (MPN)

• Chronic myelomonocytic leukemia (CMML)

• Non-Hodgkin lymphoma (NHL)

• Hodgkin lymphoma (HL) (received and failed frontline therapy or failed autologous transplantation or inability to collect enough peripheral blood stem cells [PBSC] for autologous hematopoietic cell transplant [auto-HCT])

• Multiple myeloma (MM)

• Waldenstrom's macroglobulinemia

• Severe aplastic anemia

• Histocompatible donor identified:

• Related donor or unrelated donor matched 5/6 or better (A, B, DRB1)

• Patients with benign hematological disorders such as severe aplastic anemia do not have disease requirements. Patients with malignant hematologic disorder must be in CR (MRD is allowed) with the exception of the following:

• Patients with MDS/MPN only require <5% myeloblast on bone marrow evaluation.

• Patients with AML or ALL may be in CRi, patients with MM may be in VGPR

• Have a Karnofsky performance status score of > 50%

• Diffusing capacity of the lung for carbon monoxide (DLCO) > 40% predicted, corrected for hemoglobin and/or alveolar ventilation

• Left ventricular ejection fraction > 40%

• Bilirubin =< 3 x upper limit of normal

• Liver alkaline phosphatase =< 3 x upper limit of normal

• Serum glutamic-oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) =< 3 x upper limit of normal

• Calculated creatinine clearance > 40 cc/min by the modified Cockroft-Gault formula

• Patient must be cleared pre-transplant by Radiation Oncology to be able to receive 400 cGy

• Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry; 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

• Patients who have failed a prior autologous or allogeneic transplant are eligible; however, at least 6 months must have elapsed between the start of this reduced intensity conditioning regimen and the last transplant if patient had a prior autologous or myeloablative allogeneic bone marrow transplant (BMT)

• At least 2 weeks since prior chemotherapy, radiation treatment and/or surgery

• Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

• Bone marrow failure disorders:

• Paroxysmal nocturnal hemoglobinuria (PNH)

• Hereditary bone marrow failure disorders include Diamond-Blackfan anemia, Shwachman- Diamond syndrome, Kostmann syndrome, and congenital amegakaryocytic thrombocytopenia

• Other non-malignant hematologic or immunologic disorders that require transplantation:

• Quantitative or qualitative congenital platelet disorders (including but not limited to congenital megakaryocytopenia, absent-radii syndrome, Glanzmann?s thrombasthenia)

• Quantitative or qualitative congenital neutrophil disorders (including but not limited to chronic granulomatous disease, congenital neutropenia)

• Congenital primary immunodeficiencies (including but not limited to severe combined immunodeficiency syndrome, Wiskott-Aldrich syndrome, CD40 ligand deficiency, T-cell deficiencies)

• Hemoglobinopathies (including sickle cell disease and thalassemia)

• Presence of human leukocyte antigen (HLA) antibodies

• Uncontrolled central nervous system (CNS) disease (for hematologic malignancies)

• Child-Pugh class B and C liver failure

• Patients who in the opinion of the treating physician are unlikely to comply with the restrictions of allogeneic stem cell transplantation based on formal psychosocial screening. (i.e., serious, uncontrolled psychiatric illness/social situations that would limit compliance with study requirements)

• Uncontrolled diabetes mellitus, cardiovascular disease, active serious infection or other condition which, in the opinion of treating physician, would make this protocol unreasonably hazardous for the patient

• Known human immunodeficiency virus (HIV) positive

• Pregnant or nursing female participants

• Unwilling or unable to follow protocol requirements

• Any condition which in the Investigator?s opinion deems the participant an unsuitable candidate to receive study drug