Leukemia, Lymphoma, Multiple Myeloma, Myelodysplastic Syndrome
Conditions
Keywords
Acute lymphocytic leukemia (ALL), Acute myeloid leukemia (AML), Acute Leukemia, Refractory or Relapsed AML, Myelodysplastic syndrome (MDS), Chronic myeloid leukemia (CML), Chronic myelomonocytic leukemia, Hodgkin's Lymphoma, Non-Hodgkin's lymphoma, Philadelphia-negative myeloproliferative disorder, Hematologic Malignancies, Transplantation, Busulfan, Fludarabine, Cytoxan, Bone Marrow, Allogeneic, Related donor, unrelated donor
Brief summary
The purpose of this research is to find the most effective and least toxic way to prevent GVHD after BMT.
Detailed description
A person who has cancer of the blood or lymph glands can be treated by bone marrow transplantation (BMT). BMT has developed over several decades of research on both animal and human subjects as an effective treatment of various malignant and nonmalignant hematologic diseases. Many hematologic malignancies can be successfully treated with a combination of high-dose chemotherapy or chemo-radiotherapy and transplantation of allogeneic bone marrow or peripheral blood stem cells (alloBMT) However, a possible side effect of BMT is graft versus host disease (GVHD). GVHD occurs when cells of the donor's immune system, which are present in the bone marrow, attack the BMT recipient's normal tissue. Prevention of GVHD is important for the success of the bone marrow transplant. This research is being done to find the most effective and least toxic way to prevent GVHD after BMT
Interventions
DRUGBusulfan, Fludarabine, Cytoxan
Busulfan once a day for 4 days Fludarabine once a day for 4 days Bone marrow transplant Cytoxan two doses
Sponsors
M.D. Anderson Cancer Center
Fred Hutchinson Cancer Center
Otsuka Pharmaceutical Co., Ltd.
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients ages between 0 to and 65 years of age. * Patient must have a genotypically HLA-identical sibling, a phenotypically matched first-degree relative or an unrelated matched donor. * Acute lymphocytic leukemia (ALL) in CR1 with high risk features * Acute myeloid leukemia (AML) in CR1 with high risk features defined as: i. Greater than 1 cycle of induction therapy required to achieve remission, ii. Preceding myelodysplastic syndrome (MDS) other than myelofibrosis, secondary AML iii. Presence of Flt3 mutations or internal tandem duplications, iv. FAB M6 or M7 classification or adverse cytogenetics for overall survival such as those associated with MDS, M6, M7 leukemia, or v. Complex karyotype \[\> 3 abnormalities\] * Acute Leukemias in 2nd or greater remission * Refractory or Relapsed AML * AML transformed from MDS * Myelodysplastic syndrome (MDS) beyond refractory anemia * Chronic myeloid leukemia (CML) * Chronic myelomonocytic leukemia * Philadelphia-negative myeloproliferative disorder * Relapsed chemotherapy-sensitive Hodgkin's or Non-Hodgkin's lymphoma * Multiple Myeloma-Stage III
Exclusion criteria
* Prior autologous or allogeneic stem cell transplant. * Performance status greater than 2 * Active infection. * Inadequate cardiac function; arrythmias or symptomatic cardiac disease. * Inadequate pulmonary function; FEV1, FVC, DLCO \<50% of predicted * Inadequate Serum creatinine clearance \<60 * InadequatebHepatic function * Positive serology for HIV-1, 2 or HTLV-1, 2. * Pregnancy. Female patient must have negative pregnancy test
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Determine the Optimal Regimen of Post-graft Immunosuppression With High-dose Cy Following Fludarabine, Busulfan, and Transplantation of Fully HLA-matched Bone Marrow That Leads to an Acceptable Incidence of Grades III/IV Acute GVHD | 1 year | Percentage of participants with grade III-IV acute graft versus host disease (GVHD). GVHD is graded on a combination of skin symptoms (rash), gut symptoms (diarrhea), and liver symptoms (using a lab test called bilirubin). Grades range from I to IV, where I is the least severe and IV is the most severe. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BuFlu Transplant Myeloablative bone marrow transplant with busulfan and fludarabine conditioning Post-transplantation cyclophosphamide as single-agent graft-versus-host-disease prophylaxis | 92 |
| Total | 92 |
Baseline characteristics
| Characteristic | BuFlu Transplant |
|---|---|
| Age, Continuous | 49 years |
| Region of Enrollment United States | 92 participants |
| Sex: Female, Male Female | 52 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 34 / 92 |
| serious Total, serious adverse events | 40 / 92 |
Outcome results
Primary
To Determine the Optimal Regimen of Post-graft Immunosuppression With High-dose Cy Following Fludarabine, Busulfan, and Transplantation of Fully HLA-matched Bone Marrow That Leads to an Acceptable Incidence of Grades III/IV Acute GVHD
Percentage of participants with grade III-IV acute graft versus host disease (GVHD). GVHD is graded on a combination of skin symptoms (rash), gut symptoms (diarrhea), and liver symptoms (using a lab test called bilirubin). Grades range from I to IV, where I is the least severe and IV is the most severe.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BuFlu Transplant | To Determine the Optimal Regimen of Post-graft Immunosuppression With High-dose Cy Following Fludarabine, Busulfan, and Transplantation of Fully HLA-matched Bone Marrow That Leads to an Acceptable Incidence of Grades III/IV Acute GVHD | 15 percentage of participants |