Acute Lymphocytic Leukemia, Acute Myelogenous Leukemia, Anemia, Aplastic, Chronic Lymphocytic Leukemia, Chronic Myelogenous Leukemia, Hemoglobinuria, Paroxysmal, Hodgkin's Disease, Multiple Myeloma, Myelodysplasia, Myelofibrosis, Non-Hodgkin's Lymphoma
Conditions
Keywords
Paroxysmal nocturnal hemoglobinuria, severe aplastic anemia, Mantle cell
Brief summary
The purpose of this study is to compare the effects (good and bad) of the medication basiliximab in combination with cyclosporine (investigational therapy) for the prevention of a complication of bone marrow transplantation known as graft-versus-host disease (GVHD). GVHD is a complication in which the cells of the transplanted bone marrow react against organs and tissues.
Detailed description
This study is for patients with a blood condition or myelodysplasia (bone marrow disease) which has either not responded to treatment or is not treatable by conventional/routine medical treatments. Bone marrow transplantation is a medical treatment that involves giving high doses of chemotherapy followed by the transplantation of the blood-forming and immune cells from a relative or from a matched unrelated person through the National Marrow Donor Program, in an attempt to cure disease in the recipient (the person receiving the donated cells). Nonmyeloablative (bone-marrow preservation) bone marrow transplantation is a relatively new technique in which lower than usual doses of chemotherapy are given before transplantation, in hopes of reducing adverse side effects of the chemotherapy in transplant patients. Nonmyeloablative bone marrow transplantation has several advantages which doctors have determined are beneficial for this condition. This research is being done because the complication of graft-versus-host disease can be bad for a person and there is no completely safe and effective way to prevent this complication. We know that cyclosporine helps but would like to know if the addition of basiliximab, given with cyclosporine, will decrease the incidence and/or severity of graft-versus-host disease after a transplant known as nonmyeloablative or mini transplant.
Interventions
DRUGBasiliximab
Basiliximab given 1 time on Day +7 or Day +9.
Sponsors
Indiana University School of Medicine
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
* Acute myelogenous leukemia: * Second or subsequent remission; patient over 18 yrs of age. * Relapsed after autologous HC transplant, over 18 years of age. * First remission, Philadelphia chromosome + over age 18. * Secondary AML, in first or subsequent remissions. * Acute lymphocytic leukemia: * Philadelphia chromosome + over the age of 50, first or subsequent remission. * Relapse following Autologous HC transplantation, ages over 50. * Second or subsequent remission over the age of 50 * Chronic myelogenous leukemia: * First or second chronic phase over the age of 18. * Accelerated phase over the age of 18. * Must have failed or been intolerant to a standard tyrosine kinase inhibitor. * Chronic lymphocytic leukemia: * Failed nucleoside-based therapy, ages \>18. * Myelodysplasia: * All-risk categories, age greater than 18. * Non-Hodgkin's Lymphoma, less than 76 years of age * Relapsed diffuse aggressive NHL (intermediate and high grade) that fails to achieve CR or PR to conventional salvage chemotherapy. * Aggressive NHL includes diffuse large B cell lymphoma, diffuse mixed small and large cell lymphoma, follicular lymphoma for grade 3 (follicular large cell lymphoma), T or B cell lymphoblastic lymphoma, diffuse small noncleaved (Burkett's or Burkett-like ) lymphoma, mantle cell lymphoma, peripheral T cell lymphoma, anaplastic large cell lymphoma, and other diffuse aggressive lymphomas that are not otherwise classifiable * Aggressive NHL that has relapsed following autologous HCT. Patients that respond to additional treatment for post-transplant relapse are eligible. * Aggressive NHL that does not achieve CR or PR with primary chemotherapy (i.e., primary induction failure). * Low-grade lymphoma refractory to standard therapy, including the following: 1. small cell lymphocytic lymphoma, 2. follicular lymphoma of grades 1 and 2 (follicular small cleaved and follicular mixed small and large cell lymphoma) 3. marginal cell lymphoma, splenic lymphoma), 4. lymphoplasmacytic lymphoma and 5. other lymphomas not otherwise classifiable. * Patients with low-grade lymphoma must have experienced progressive disease after receiving three or more of the following regimens: * alkylator-based therapy (cyclophosphamide/ vincristine/ prednisone) chlorambucil, monoclonal antibody based therapy (e.g., rituximab, Campath-1H, radiolabelled CD20+ antibodies); * nucleoside analog-based therapy (e.g., fludarabine, cladribine).) * Patients with marginal zone lymphoma or gastric MALT type associated with Helicobacter pylori infection must have progressed after receiving appropriate antibiotic therapy as well as three or more regimens as described above * Mantle cell, ages 18-75. * Hodgkin's Disease, ages 18-75. * Relapsed or refractory disease after autologous transplant. * Multiple Myeloma, ages 18-75 * Recurrent disease after two medical therapies * Relapse following autologous transplant * Myelofibrosis, age greater than 18 years * Severe aplastic anemia (refractory to immunosuppressive therapy); age greater than 18 years * Patients with aplastic anemia must have marrow cellularity ≤ 10% plus 2 of the following: 1. Absolute granulocyte count \<500/mm3 2. Corrected reticulocyte count \<1% 3. Untransfused platelet count \<20,000/mm3 on at least 2 occasions 4. Hemoglobin \<9 g/dL (adults) or \< 8 g/dL (children) on at least 2 occasions * Paroxysmal nocturnal hemoglobinuria; age greater than 18 years. * Renal function: creatinine greater than 2.5 * Donor Requirement: * Must have a fully HLA-matched (10 of 10 Antigen matched) related or unrelated donor, eighteen years of age or older, who is capable of undergoing GCSF mobilization and apheresis
Exclusion criteria
* Active CNS disease (the presence of leukemic blasts in the CSF) * Pregnancy or breast-feeding. * Inability to give informed consent. * AST, ALT, total bilirubin \>3x upper limit of normal. * Creatinine \> 2 or creatinine clearance \< 50mL/hr. If patient has a creatinine of \> 2 or creatinine clearance \< 50mL/hr and it is due to the disease process then the patient will not be excluded based on this. * Fractional shortening by echocardiogram not within normal limits per institution or LVEF of \< 40 %. * Pulmonary function: DLCO not within institutional normal limits or DLCO less than 45% of normal predicted, corrected for anemia * Prior allogeneic transplant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Grade 3-4 Acute GVHD Rate | Transplant (Day 0) up to 1 year | The percent of patients where a patient experienced a Grade 3 or 4 acute GVHD |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Neutrophil Engraftment | Transplant (Day 0) up to 1 year | Time to neutrophil engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of neutrophils is defined as the time from day 0 to the date of the first of three consecutive days after transplantation during which the absolute neutrophils count (ANC) is at least 0.5 x109/l. Patients who did not have neutrophil engraftment before death will be censored at the date of death. The median and 95% confidence intervals will be provided. |
| Time to Platelet Engraftment | Transplant (Day 0) up to 1 year | Time to platelet engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of platelets is defined as the time from day 0 to the first of seven consecutive days after transplantation during which the platelet count is at least 20 x109/l without transfusion support. Patients who did not have platelet engraftment before death will be censored at the date of death. The median and 95% confidence intervals will be provided. |
Countries
United States
Participant flow
Recruitment details
This protocol has 17 patients. The study was stopped prior to 20 due to the meeting of a stopping rule of 5 or more deaths within the first 15 patients. An additional patient was enrolled after the stopping rule was met. This patient was followed for safety/AE but is not included in the analysis of the efficacy measures, as recommended by the IRB.
Participants by arm
| Arm | Count |
|---|---|
| Overall Patients administered 40 mg of basiliximab as a single intravenous dose on day +7, +8, or +9 following infusion of allogeneic peripheral blood hematopoietic cells | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 6 |
Baseline characteristics
| Characteristic | Overall |
|---|---|
| Age, Continuous | 59.1 years STANDARD_DEVIATION 7.05 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 17 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 17 / 17 |
| serious Total, serious adverse events | 7 / 17 |
Outcome results
Primary
Grade 3-4 Acute GVHD Rate
The percent of patients where a patient experienced a Grade 3 or 4 acute GVHD
Time frame: Transplant (Day 0) up to 1 year
Population: All patients enrolled and received treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Overall | Grade 3-4 Acute GVHD Rate | 29.4 percentage of participants |
Secondary
Time to Neutrophil Engraftment
Time to neutrophil engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of neutrophils is defined as the time from day 0 to the date of the first of three consecutive days after transplantation during which the absolute neutrophils count (ANC) is at least 0.5 x109/l. Patients who did not have neutrophil engraftment before death will be censored at the date of death. The median and 95% confidence intervals will be provided.
Time frame: Transplant (Day 0) up to 1 year
Population: All patients enrolled and received treatment, excluding the patient who entered after the stopping rule was met.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Overall | Time to Neutrophil Engraftment | 13.5 days |
Secondary
Time to Platelet Engraftment
Time to platelet engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of platelets is defined as the time from day 0 to the first of seven consecutive days after transplantation during which the platelet count is at least 20 x109/l without transfusion support. Patients who did not have platelet engraftment before death will be censored at the date of death. The median and 95% confidence intervals will be provided.
Time frame: Transplant (Day 0) up to 1 year
Population: All patients enrolled and received treatment, excluding the patient who entered after the stopping rule was met.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Overall | Time to Platelet Engraftment | 12.0 days |