Clinical trial NCT02065154: Post Transplant Cyclophosphamide (Cytoxan) for GvHD Prophylaxis
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Lymphoma
Myelodysplastic Syndrome
Myelofibrosis
Severe Aplastic Anemia
Allogeneic Transplant
Keywords: 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
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2014-02-17
Enrollment: 39
Sex: ALL
Minimum age (years): 19
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Grade II-IV Acute GVHD
timeFrame: Till 100 days post transplant
Secondary outcomes:
measure: Overall Survival
timeFrame: 2 Year Post Transplant
measure: Disease-free Survival
timeFrame: 1 Year Post-transplant
measure: Regimen Related Toxicity
timeFrame: 100 Days Post Transplant
measure: Relapse Rate
timeFrame: 2 years post-transplant
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Bone Marrow Transplantation and Cellular Therapy Program
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Racquel D Innis-Shelton, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jamy O, Innis-Shelton R, Bal S, Paluri R, Salzman D, Di Stasi A, Costa L, Meredith R, Lamb L, Minagawa K, Mineishi S, Saad A. Phase II clinical trial of one dose of post-transplant cyclophosphamide for graft versus host disease prevention following myeloablative, peripheral blood stem cell, matched-unrelated donor transplantation. Am J Hematol. 2021 Oct 1;96(10):E396-E398. doi: 10.1002/ajh.26296. Epub 2021 Jul 31. No abstract available.