Graft Versus Host Disease, Hematopoietic/Lymphoid Cancer
Conditions
Brief summary
This pilot clinical trial studies donor stem cell transplant followed by cyclophosphamide in treating patients with hematological diseases. Giving chemotherapy before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Giving cyclophosphamide after the transplant may stop this from happening.
Detailed description
PRIMARY OBJECTIVES: I. To determine if haploidentical stem cell transplant using post-transplant cyclophosphamide results in 60% or better disease free survival (DFS) at 12 months at our institution. SECONDARY OBJECTIVES: I. To determine the rate of acute and chronic graft-versus-host disease (GvHD), non-relapse mortality, and relapse. OUTLINE: PREPARATIVE REGIMEN: Patients receive fludarabine phosphate intravenously (IV) once daily (QD) on days -6 to -2. Patients receiving myeloablative conditioning receive busulfan IV every 6 hours for 16 doses on days -7 to -4 and patients receiving reduced intensity conditioning receive busulfan IV every 6 hours for 8 doses on days -5 to -4. Patients also receive cyclophosphamide IV QD on days -3 and -2 TRANSPLANT: Patients undergo stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclophosphamide QD on days 3 and 4, tacrolimus on days 5-180, and mycophenolate mofetil on days 5-35. After completion of study treatment, patients are followed up periodically for 2 years.
Interventions
DRUGfludarabine phosphate
Given IV
DRUGbusulfan
Given IV
DRUGcyclophosphamide
Given IV
PROCEDUREallogeneic hematopoietic stem cell transplantation
Undergo myeloablative or reduced intensity allogeneic stem cell transplant
DRUGtacrolimus
DRUGmycophenolate mofetil
Sponsors
National Cancer Institute (NCI)
Wake Forest University Health Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of a hematological malignancy requiring an allogeneic stem cell transplant consistent with the standard of care * Remission of any acute hematologic malignancy or adequate disease control for chronic malignancies. * Ages 18-69 years old. * Available familial haploidentical (4 to 6 out of 8 HLA loci-matched) donor
Exclusion criteria
* Significant organ dysfunction defined as: LV EF \< 50% (evaluated by echocardiogram or MRI), DLCO or FEV1 \< 65% predicted, AST/ALT \> 2.5 x ULN, Bilirubin \> 1.5 x ULN, Serum creatinine \> 2mg/dL, dialysis, or prior renal transplant * HIV positive (Recipients who are positive for hepatitis B (HBV), hepatitis C (HCV) or human T-cell lymphotropic virus (HTLV-I/II) are not excluded from participation) * Positive pregnancy test for women of childbearing age. * Major anticipated illness or organ failure incompatible with survival form transplant. * Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the transplant treatment unlikely and informed consent impossible.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 12 Month Disease Free Survival Probability | At 12 months | The percentage of patients who experience death or disease relapse by one year will be calculated and a corresponding 95% confidence interval will be constructed using the normal approximation for binomial proportions. The survival function will be estimated and plotted using the method of Kaplan and Meier. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | At 12 months | Kaplan-Meier estimation of the percentage of patients who are alive without progressive disease at one year. |
| Rate of Acute GvHD | 12 months | Kaplan-Meier estimation of the rate of acute GvHD in the study population at one year with a 95% confidence interval. |
| Overall Survival | At 12 months | The survival function will be estimated and plotted using the method of Kaplan and Meier. |
| Relapse-free Mortality | At 12 months | Non-relapse mortality will be defined as time from registration to death due to anything other than relapse of hematological malignancy. Patients who relapse will be treated as a competing risk. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Stem Cell Transplant With GVHD Prophylaxis) PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV QD on days -6 to -2. Patients receiving myeloablative conditioning receive busulfan IV every 6 hours for 16 doses on days -7 to -4 and patients receiving reduced intensity conditioning receive busulfan IV every 6 hours for 8 doses on days -5 to -4. Patients also receive cyclophosphamide IV QD on days -3 and -2
TRANSPLANT: Patients undergo stem cell transplant on day 0.
GVHD PROPHYLAXIS: Patients receive cyclophosphamide QD on days 3 and 4, tacrolimus on days 5-180, and mycophenolate mofetil on days 5-35. Allogeneic hematopoietic stem cell transplantation
fludarabine phosphate: Given IV
busulfan: Given IV
cyclophosphamide: Given IV
allogeneic hematopoietic stem cell transplantation: Undergo myeloablative or reduced intensity allogeneic stem cell transplant
tacrolimus
mycophenolate mofetil | 27 |
| Total | 27 |
Baseline characteristics
| Characteristic | Treatment (Stem Cell Transplant With GVHD Prophylaxis) |
|---|---|
| Age, Continuous | 53.4 years STANDARD_DEVIATION 14.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 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 | 7 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 | 2 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Region of Enrollment United States | 27 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 13 / 27 |
| other Total, other adverse events | 27 / 27 |
| serious Total, serious adverse events | 27 / 27 |
Outcome results
Primary
12 Month Disease Free Survival Probability
The percentage of patients who experience death or disease relapse by one year will be calculated and a corresponding 95% confidence interval will be constructed using the normal approximation for binomial proportions. The survival function will be estimated and plotted using the method of Kaplan and Meier.
Time frame: At 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Stem Cell Transplant With GVHD Prophylaxis) | 12 Month Disease Free Survival Probability | 51.8 percentage of participants |
Secondary
Overall Survival
The survival function will be estimated and plotted using the method of Kaplan and Meier.
Time frame: At 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Stem Cell Transplant With GVHD Prophylaxis) | Overall Survival | 66.7 percentage of participants |
Secondary
Progression Free Survival
Kaplan-Meier estimation of the percentage of patients who are alive without progressive disease at one year.
Time frame: At 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Stem Cell Transplant With GVHD Prophylaxis) | Progression Free Survival | 51.8 percentage of participants |
Secondary
Rate of Acute GvHD
Kaplan-Meier estimation of the rate of acute GvHD in the study population at one year with a 95% confidence interval.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Stem Cell Transplant With GVHD Prophylaxis) | Rate of Acute GvHD | 51.8 percentage of participants |
Secondary
Relapse-free Mortality
Non-relapse mortality will be defined as time from registration to death due to anything other than relapse of hematological malignancy. Patients who relapse will be treated as a competing risk.
Time frame: At 12 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment (Stem Cell Transplant With GVHD Prophylaxis) | Relapse-free Mortality | 86.8 days |