Post Transplant Cyclophosphamide (Cytoxan) for GvHD Prophylaxis

Phase 2

Completed

Conditions: Severe Aplastic Anemia
Leukemia
Myelodysplastic Syndrome
Myelofibrosis
Allogeneic Transplant
Lymphoma

Brief Summary: The main purpose of this study is to assess the effects of cyclophosphamide (cytoxan) in the post transplant setting to prevent onset of acute graft-versus-host disease (GVHD). The primary objective is to determine the incidence of grade II-IV acute GVHD following Allogeneic (allo) Hematopoeitic Cell Transplant (HCT) using post-transplant cyclophosphamide (cytoxan) for patients with human leukocyte antigen (HLA) matched unrelated (MUD) and mismatched unrelated (MMUD) donors. Other objectives for this study will be the determination of disease-free survival (DFS) and overall survival (OS) following allo HCT and assess the safety of post-transplant cyclophosphamide (cytoxan) for MUD and MMUD transplantation. Disease recurrence and time to recurrence in patients receiving post-transplant cyclophosphamide compared to historical control without post-transplant cyclophosphamide (cytoxan) will also be evaluated. Other objectives will be to determine the time of onset, severity, responsiveness to treatment, organs involved of acute and chronic GVHD as well as observation of Immune Reconstitution over time.

Detailed Description: he main purpose of this study is to assess the effects of cyclophosphamide (cytoxan) in the post transplant setting to prevent onset of acute graft-versus-host disease (GVHD). The primary objective is to determine the incidence of grade II-IV acute GVHD following Allogeneic (allo) Hematopoeitic Cell Transplant (HCT) using post-transplant cyclophosphamide (cytoxan) for patients with human leukocyte antigen (HLA) matched unrelated (MUD) and mismatched unrelated (MMUD) donors. Other objectives for this study will be the determination of disease-free survival (DFS) and overall survival (OS) following allo HCT and assess the safety of post-transplant cyclophosphamide (cytoxan) for MUD and MMUD transplantation. Disease recurrence and time to recurrence in patients receiving post-transplant cyclophosphamide compared to historical control without post-transplant cyclophosphamide (cytoxan) will also be evaluated. Other objectives will be to determine the time of onset, severity, responsiveness to treatment, organs involved of acute and chronic GVHD as well as observation of Immune Reconstitution over time.

Recruitment & Eligibility

Inclusion Criteria

Disease Criteria: patients must meet diagnostic criteria of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), myelodysplastic syndrome (MDS), myelofibrosis, or severe aplastic anemia. Patients will be allowed on study if they are deemed eligible for allo HCT regardless of remission status.
Age Criteria: 19 to 65 years in age.
Organ Function Criteria: All organ function testing should be done within 28 days of study registration.
Cardiac: Left ventricular ejection fraction (LVEF) ≥ 50% by MUGA (Multi Gated Acquisition) scan or echocardiogram.
Pulmonary: FEV1 (Forced expiratory volume in 1 second) and FVC (Forced vital capacity) ≥ 50% predicted, DLCO (diffusing capacity of the lung for carbon monoxide) (corrected for hemoglobin) ≥ 50% of predicted.
Renal: The estimated creatinine clearance (CrCl) must be equal or greater than 60 mL/min/1.73 m2 as calculated by the Cockcroft-Gault Formula:

CrCl=(140-age) x weight(kg) x 0.85 (if female)/72 x serum creatinine (mg/dL)

Hepatic:
- Serum bilirubin 1.5 upper limit of normal (ULN)
- Aspartate transaminase (AST)/alanine transaminase (ALT) 2.5 ULN
- Alkaline phosphatase 2.5 ULN
Performance status: Karnofsky ≥ 70%.,
Patient must be informed of the investigational nature of this study in accordance with institutional and federal guidelines and have the ability to provide written informed consent prior to initiation of any study-related procedures, and ability, in the opinion of the principal investigator, to comply with all the requirements of the study.
Patient has a suitable and willing HLA-8/8 matched or 6/8 mismatched (at one allele) unrelated donor identified.

Exclusion Criteria

Non-compliant to medications.
No appropriate caregivers identified.
HIV1 (Human Immunodeficiency Virus-1) or HIV2 positive
Uncontrolled medical or psychiatric disorders.
Uncontrolled infections, defined as positive blood cultures within 72 hours of study entry, or evidence of progressive infection by imaging studies such as chest CT scan within 14 days of registration.
Active central nervous system (CNS) leukemia.
Preceding allogeneic HSCT.
Pregnancy or Breastfeeding.

Arm && Interventions

Group	Intervention	Description
Cyclophosphamide (Cytoxan)	Cyclophosphamide	Cyclophosphamide (Cytoxan)

Primary Outcome Measures

Name	Time	Method
Grade II-IV Acute GVHD	Till 100 days post transplant	To calculate the percentage of patients developing graft versus host disease, grade II-IV, in the first 100 days after transplant

Secondary Outcome Measures

Name	Time	Method
Overall Survival	2 Year Post Transplant	What percentage of participants were alive at a certain time point after transplant
Disease-free Survival	1 Year Post-transplant	What percentage of participants did not have relapse of disease after transplant
Regimen Related Toxicity	100 Days Post Transplant	Number of toxicities experienced by the patients in the study
Relapse Rate	2 years post-transplant	What percentage of participants relapsed

Locations (1): UAB Bone Marrow Transplantation and Cellular Therapy Program
🇺🇸
Birmingham, Alabama, United States