Allogeneic Transplant, Leukemia, Lymphoma, Myelodysplastic Syndrome, Myelofibrosis, Severe Aplastic Anemia
Conditions
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
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.
Interventions
DRUGCyclophosphamide
Sponsors
University of Alabama at Birmingham
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Cyclophosphamide (Cytoxan)
Cyclophosphamide | 39 |
| Total | 39 |
Baseline characteristics
| Characteristic | Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 39 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 33 Participants |
| Region of Enrollment United States | 39 participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 19 / 39 |
| other Total, other adverse events | 0 / 39 |
| serious Total, serious adverse events | 8 / 39 |
Outcome results
Primary
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
Time frame: Till 100 days post transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Grade II-IV Acute GVHD | 30 percentage of participants |
Secondary
Disease-free Survival
What percentage of participants did not have relapse of disease after transplant
Time frame: 1 Year Post-transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Disease-free Survival | 46.15 percentage of participants |
Secondary
Overall Survival
What percentage of participants were alive at a certain time point after transplant
Time frame: 2 Year Post Transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Overall Survival | 51 percentage of participants |
Secondary
Regimen Related Toxicity
Number of toxicities experienced by the patients in the study
Time frame: 100 Days Post Transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Regimen Related Toxicity | 6 Number of toxicities |
Secondary
Relapse Rate
What percentage of participants relapsed
Time frame: 2 years post-transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Relapse Rate | 21 percentage of participants |