Hematologic Neoplasms
Conditions
Keywords
Chronic Myelogenous Leukemia, Acute Myelogenous Leukemia, Myelodysplastic Syndrome, Myelofibrosis, Acute Lymphocytic Leukemia, Acute Lymphoblastic Lymphoma, Chronic Lymphocytic Leukemia, Prolymphocytic Leukemia, Low-grade non-Hodgkin's Lymphoma, Mantle Cell Lymphoma, Hodgkin Lymphoma, Myeloma
Brief summary
This trial will evaluate the safety and efficacy of post-transplant Cy and sirolimus following reduced intensity allogeneic SCT. It is hoped that the combination of a reduced intensity preparative regimen with a calcineurin-free GVHD prophylaxis regimen will decrease the risk of acute and chronic GVHD, by both limiting mucosal toxicity and augmenting immune reconstitution, thereby improving the safety of the procedure. The past experience with post-transplant Cy suggests that SCT recipients will attain rapid donor T cell chimerism, which the investigators hope will translate into improved disease control through the well documented graft-versus-malignancy effects of donor T cells.
Interventions
PROCEDUREAllogeneic Hematopoietic Stem Cell Transplantation
Patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis.
Sponsors
Blood and Marrow Transplant Group of Georgia
Northside Hospital, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Availability of a 7/8 or 8/8 (HLA-A, B, C, DR) related or unrelated donor * Age 18-75 * One of the following high-risk malignancies * Chronic Myelogenous Leukemia * Acute Myelogenous Leukemia * Myelodysplastic Syndrome * Myelofibrosis * Acute Lymphocytic Leukemia * Acute Lymphoblastic Lymphoma * Chronic Lymphocytic Leukemia * Prolymphocytic Leukemia * Low-grade non-Hodgkin's Lymphoma * Mantle Cell Lymphoma * Hodgkin Lymphoma * Myeloma
Exclusion criteria
* Poor cardiac function (EF \<40%) * Poor pulmonary function (FEV1 and FVC \<50% predicted) * Poor liver function (bilirubin \>/= 2 mg/dl not due to hemolysis, Gilbert's or primary malignancy) * Poor renal function (creatinine \>/= 2 mg/dl or creatinine clearance \<40mL/min) * Karnofsky status \<70% * HIV positive
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of GVHD | 1 year | To estimate the incidence of graft-versus-host disease (GVHD) when utilizing post-transplant cyclophosphamide (Cy) and sirolimus for GVHD prophylaxis following reduced intensity allogeneic hematopoietic stem cell transplantation (SCT) in patients with high risk hematologic malignancies. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Absolute Neutrophil Count (ANC)/Platelet Engraftment | Approximately Day 30 | To estimate the incidence of neutrophil and platelet engraftment |
| Number of Participants With Non-Relapse Mortality | 1 year | — |
| Number of Patients With Disease Free Survival at 2 Years | 2 years | — |
| Number of Patients to Achieve Full Donor Chimerism | 1 year | Characterize rate of achievement of full donor chimerism |
| Number of Patients With Overall Survival at 2 Years. | 2 years | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Reduced Intensity Allogeneic Stem Cell Transplantation All patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis.
Allogeneic Hematopoietic Stem Cell Transplantation: Patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis. | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | Progression of disease post treatment | 6 |
Baseline characteristics
| Characteristic | Reduced Intensity Allogeneic Stem Cell Transplantation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants |
| Age, Continuous | 61 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 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 | 5 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 | 21 Participants |
| Region of Enrollment United States | 26 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 26 / 26 |
| serious Total, serious adverse events | 10 / 26 |
Outcome results
Primary
Incidence of GVHD
To estimate the incidence of graft-versus-host disease (GVHD) when utilizing post-transplant cyclophosphamide (Cy) and sirolimus for GVHD prophylaxis following reduced intensity allogeneic hematopoietic stem cell transplantation (SCT) in patients with high risk hematologic malignancies.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reduced Intensity Allogeneic Stem Cell Transplantation | Incidence of GVHD | 12 participants |
Secondary
Incidence of Absolute Neutrophil Count (ANC)/Platelet Engraftment
To estimate the incidence of neutrophil and platelet engraftment
Time frame: Approximately Day 30
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reduced Intensity Allogeneic Stem Cell Transplantation | Incidence of Absolute Neutrophil Count (ANC)/Platelet Engraftment | 26 participants |
Secondary
Number of Participants With Non-Relapse Mortality
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reduced Intensity Allogeneic Stem Cell Transplantation | Number of Participants With Non-Relapse Mortality | 1 participants |
Secondary
Number of Patients to Achieve Full Donor Chimerism
Characterize rate of achievement of full donor chimerism
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reduced Intensity Allogeneic Stem Cell Transplantation | Number of Patients to Achieve Full Donor Chimerism | 26 participants |
Secondary
Number of Patients With Disease Free Survival at 2 Years
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reduced Intensity Allogeneic Stem Cell Transplantation | Number of Patients With Disease Free Survival at 2 Years | 17 participants |
Secondary
Number of Patients With Overall Survival at 2 Years.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reduced Intensity Allogeneic Stem Cell Transplantation | Number of Patients With Overall Survival at 2 Years. | 19 participants |