Anemia, Aplastic, Hematologic Neoplasms, Hemoglobinuria, Paroxysmal, Multiple Myeloma, Myelofibrosis
Conditions
Keywords
Hematologic malignancies, lymphoma, leukemia, MDS (myelodysplastic syndrome), reduced-intensity preparative regimen, allogeneic peripheral blood stem cell transplant, myelofibrosis or other myeloproliferative syndromes
Brief summary
The purpose of this study is to look at whether the combination of lower-dose chemotherapy with two chemotherapy (anti-cancer) drugs, called busulfan and melphalan, and an antibody medication called alemtuzumab (Campath®), can prevent rejection of donor blood stem cells so that those cells take hold and build a healthy new blood cell factory after transplant. The study will also look at the safety of the combination of drugs and of the transplant of peripheral blood stem cells from a healthy relative or an unrelated donor.
Detailed description
Transplantation of related or unrelated allogeneic peripheral blood stem cells (PBSCs) after administration of a reduced-intensity regimen of busulfan, melphalan and alemtuzumab will be associated with satisfactory engraftment and acceptable post-transplant non-relapse mortality.
Interventions
DRUGbusulfan, and melphalan, and alemtuzumab
intravenous busulfan 3.2 mg/kg/dose daily for 2 days, on days -5 and -4 (i.e., 5 and 4 days, respectively, before PBSCT). intravenous melphalan 100 mg/m2 on day -3. intravenous alemtuzumab 30 mg/dose for 2 days, on days -2 and -1.
Sponsors
University of Arizona
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
* Age 50 to 75 years or age 18 to 49 with one or more of these risk factors: prior autologous, allogeneic or syngeneic HCT (Hematopoietic cell transplantation); not in first complete remission or first chronic phase; and/or presence of one or more medical conditions that would place the subject at high risk such as heart and kidney disease. * Subjects with hematologic cancers must have received at least one previous course of chemotherapy or biological therapy. In other words, the subject cannot enroll in this trial for initial treatment of the disease. * Availability of a healthy related or unrelated volunteer allogeneic donor.
Exclusion criteria
* Eligible for another study or standard of care treatment that offers higher probability of cure or long-term control of subject's disease. * Severe abnormal function of organs such as heart, kidneys, liver. * Untreated or progressive central nervous system involvement by the disease. * Subject is pregnant or breast-feeding. * Performance score is below 50: at the least, requires considerable assistance and frequent medical care. * Positive for the HIV \[AIDS\] virus * Life expectancy less than 12 weeks with conventional treatments. * For subjects capable of having children, refusal to practice birth control while on this study and for at least 12 months after PBSCT or after stopping post-transplant immunosuppressive treatments, whichever occurs later.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Presence of Donor Lymphohematopoietic Chimerism (Defined as at Least 50% Donor Cells in the Peripheral Blood) in Peripheral Blood by Day +100 (i.e., 100 Days After Allogeneic PBSCT). | Day +100 | To determine the efficacy of related or unrelated allogeneic PBSC transplantation (PBSCT) using a preparative regimen of busulfan, melphalan and alemtuzumab, as measured by durable donor lymphohematopoietic cell engraftment. The primary efficacy endpoint is the presence of donor lymphohematopoietic chimerism (defined as at least 50% donor cells in the peripheral blood) in peripheral blood by day +100 (i.e., 100 days after allogeneic PBSCT). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Relapse-free Survival. | Day +100 | To determine the safety of related or unrelated allogeneic PBSCT using a preparative regimen of busulfan, melphalan and alemtuzumab. The primary safety endpoint is non-relapse mortality at day +100. |
| Number of Participants With Event-free Survival. | Day +100 | To determine the safety of related or unrelated allogeneic PBSCT using a preparative regimen of busulfan, melphalan and alemtuzumab. The primary safety endpoint is non-relapse mortality at day +100. |
| Number of Participants With Overall Survival. | Day +100 | To determine the safety of related or unrelated allogeneic PBSCT using a preparative regimen of busulfan, melphalan and alemtuzumab. The primary safety endpoint is non-relapse mortality at day +100. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Busulfan, and Melphalan, and Alemtuzumab Three drug regimen using busulfan, and melphalan, and alemtuzumab.
Busulfan, and melphalan, and alemtuzumab: intravenous busulfan 3.2 mg/kg/dose daily for 2 days, on days -5 and -4 (i.e., 5 and 4 days, respectively, before PBSCT).
Intravenous melphalan 100 mg/m2 on day -3.
Intravenous alemtuzumab 30 mg/dose for 2 days, on days -2 and -1. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 7 |
Baseline characteristics
| Characteristic | Busulfan, and Melphalan, and Alemtuzumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 9 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 16 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 16 |
| other Total, other adverse events | 16 / 16 |
| serious Total, serious adverse events | 3 / 16 |
Outcome results
Primary
Number of Participants With Presence of Donor Lymphohematopoietic Chimerism (Defined as at Least 50% Donor Cells in the Peripheral Blood) in Peripheral Blood by Day +100 (i.e., 100 Days After Allogeneic PBSCT).
To determine the efficacy of related or unrelated allogeneic PBSC transplantation (PBSCT) using a preparative regimen of busulfan, melphalan and alemtuzumab, as measured by durable donor lymphohematopoietic cell engraftment. The primary efficacy endpoint is the presence of donor lymphohematopoietic chimerism (defined as at least 50% donor cells in the peripheral blood) in peripheral blood by day +100 (i.e., 100 days after allogeneic PBSCT).
Time frame: Day +100
Population: Data were collected but could not be analyzed. PI for this study has retired and any data that were gathered, are lost. No data are available for this assessment
Secondary
Number of Participants With Event-free Survival.
To determine the safety of related or unrelated allogeneic PBSCT using a preparative regimen of busulfan, melphalan and alemtuzumab. The primary safety endpoint is non-relapse mortality at day +100.
Time frame: Day +100
Population: Data were collected but could not be analyzed. PI for this study has retired and any data that were gathered, are lost. No data are available for this assessment
Secondary
Number of Participants With Overall Survival.
To determine the safety of related or unrelated allogeneic PBSCT using a preparative regimen of busulfan, melphalan and alemtuzumab. The primary safety endpoint is non-relapse mortality at day +100.
Time frame: Day +100
Population: Data were collected but could not be analyzed. PI for this study has retired and any data that were gathered, are lost. No data are available for this assessment
Secondary
Number of Participants With Relapse-free Survival.
To determine the safety of related or unrelated allogeneic PBSCT using a preparative regimen of busulfan, melphalan and alemtuzumab. The primary safety endpoint is non-relapse mortality at day +100.
Time frame: Day +100
Population: Data were collected but could not be analyzed. PI for this study has retired and any data that were gathered, are lost. No data are available for this assessment.