Post Transplant Cyclophosphamide (Cytoxan) for GvHD Prophylaxis

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase II Clinical Trial of the Use of Post-Transplant Cyclophosphamide for Graft Versus Host Disease (GvHD) Prophylaxis Following Matched Unrelated Donor (MUD) and Mismatched Unrelated Donor (MMUD)Hematopoietic Stem Cell Transplant (HSCT)

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

Intervention / Treatment
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* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cyclophosphamide (Cytoxan)<br>Cyclophosphamide (Cytoxan) | Drug: Cyclophosphamide<br> <br> * Other names: Cytoxan;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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, severe aplastic anemia