Leukemia, Lymphoma, Myeloma
Conditions
Keywords
Cancers of the blood
Brief summary
The purpose of this study is: 1. To establish the maximally tolerated dose (MTD) of intravenous busulfan (Busulfan®) in combination with fludarabine as conditioning regimen for transplantation with in-vivo T-cell depletion. 2. To evaluate disease free and overall survival after this conditioning regimen in patients with advanced acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). 3. To evaluate potential pharmacogenomic determinants of toxicity of this regimen. 4. To evaluate potential pharmacogenomic determinants of efficacy of this regimen.
Interventions
DRUGBusulfan
Daily intravenous dosing to target AVC
DRUGFludarabine
Fludarabine dosing will be based on actual body weight. Fludarabine will be infused over 30 minutes before busulfan treatment dose.
DRUGCampath
All patients will receive premedication for Campath (daily doses of 20 mg are repeated for up to five times).
PROCEDUREStem Cell Transplant
Infusion of bone marrow and donors(related/ unrelated).
Sponsors
University of Chicago
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Phase I portion: * Relapsed or refractory acute myelogenous or lymphoid leukemia. * Chronic myelogenous leukemia in accelerated phase or blast-crisis. * Recurrent or refractory malignant lymphoma or Hodgkin's disease * Recurrent or refractory multiple myeloma. * Chronic lymphocytic leukemia, relapsed or with poor prognostic features. * Myeloproliferative disorder (polycythemia vera, myelofibrosis) with transformation * Myelodysplastic syndromes with more than 5% blasts. Phase II portion: * AML with active disease or beyond CR2. * MDS with more than 5% blasts.
Exclusion criteria
* Clinical progression. Such patients may be treated on other treatment protocols or at the investigator's discretion. Such patients will continue to be monitored for survival and, may be asked to continue to provide specimens for studies of minimal residual disease and immune reconstitution as other treatments are recommended.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose | 5 years | Maximally tolerated area under the curve of intravenous busulfan (Busulfan®) in combination with fludarabine as conditioning regimen for transplantation with in-vivo T-cell depletion. The number reported will be an Area Under the Curve (AUC) measure reported in µmol-min/L. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 5 years | Overall Survival measured as median survival in days |
| Disease Free Survival | 5 years | Disease Free Survival measured by median survival time in days |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Busulfan and Fludarabine Intravenous busulfan (Busulfan®) in combination with fludarabine
Busulfan: Daily intravenous dosing to target AVC
Fludarabine: Fludarabine dosing will be based on actual body weight. Fludarabine will be infused over 30 minutes before busulfan treatment dose.
Campath: All patients will receive premedication for Campath (daily doses of 20 mg are repeated for up to five times).
Stem Cell Transplant: Infusion of bone marrow and donors(related/ unrelated). | 50 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
Baseline characteristics
| Characteristic | Busulfan and Fludarabine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 46 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 3 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 | 5 Participants |
| Race (NIH/OMB) White | 39 Participants |
| Region of Enrollment United States | 50 participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 45 / 49 |
| other Total, other adverse events | 1 / 49 |
| serious Total, serious adverse events | 1 / 49 |
Outcome results
Primary
Maximum Tolerated Dose
Maximally tolerated area under the curve of intravenous busulfan (Busulfan®) in combination with fludarabine as conditioning regimen for transplantation with in-vivo T-cell depletion. The number reported will be an Area Under the Curve (AUC) measure reported in µmol-min/L.
Time frame: 5 years
Population: The 36 patients refer to the phase I portion of the study only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Busulfan and Fludarabine | Maximum Tolerated Dose | 6800 mmol-min/L |
Secondary
Disease Free Survival
Disease Free Survival measured by median survival time in days
Time frame: 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Busulfan and Fludarabine | Disease Free Survival | 172 days |
Comparison: Estimated median survival time95% CI: [85, 436]
Secondary
Overall Survival
Overall Survival measured as median survival in days
Time frame: 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Busulfan and Fludarabine | Overall Survival | 161 days |
95% CI: [121, 305]Product limit survival estimate