Leukemia, Lymphoma, Myelodysplastic Syndrome
Conditions
Keywords
Stem Cell Transplant, Allogeneic Transplant, Donors
Brief summary
A common problem after stem cell transplant is graft-versus-host-disease (GVHD). GVHD is a complication of transplantation where the donor graft attacks and damages some of your tissues. After stem cell transplant, all patients receive prophylactic medications against GVHD. In this research study, we are studying the safety and effectiveness of a bortezomib based GVHD prophylaxic drug combination in participants after myeloablative allogeneic stem call transplantation from a matched unrelated donor, mismatched related or unrelated donor.
Detailed description
Before your transplant you will receive conditioning therapy with fludarabine and busulfan given 7, 6, 5, and 4 days before your transplant. On day 0, you will receive selected blood cells taken from your sibling or unrelated donor. You will receive 3 drugs for your GVHD prophylaxis: Tacrolimus will be started 3 days before your transplant. It will be given intravenously and later by mouth. You will continue to take tacrolimus for 3 to 6 months after transplant. Methotrexate will be given intravenously 1, 3, 6 and 11 days after your transplant. Bortezomib will be given intravenously 1, 4, and 7 days after your transplant. On days 1, 4, 7, 30 and 3, 6 and 12 months after your transplant you will have a physical exam, blood work, and be asked to complete a questionnaire.
Interventions
DRUGBortezomib
Bortezomib 1.3 mg/m\^2 IV
DRUGTacrolimus
Tacrolimus 0.05 mg/kg PO bid
DRUGMethotrexate
Methotrexate 15 mg/m\^2 IV
Sponsors
Dana-Farber Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed advanced and/or aggressive hematologic malignancy (including myelodysplastic syndrome) that is unlikely to be cured by alternative therapies * HLA-Matched unrelated donor; or 1-locus HLA-mismatched related or unrelated donor * ECOG performance status 0-2 * Adequate organ function * Able to understand and willing to sign a written informed consent document * Agrees to practice adequate contraception per study requirements
Exclusion criteria
* Pregnant or breastfeeding * Recipient of prior allogeneic or autologous stem cell transplantation * Prior abdominal radiation therapy * HIV-positive on combination antiretroviral therapy * Seropositive for hepatitis B or C * Allergies to bortezomib, boron, or mannitol * Myocardial infarction within last 6 months, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias * Uncontrolled bacterial, viral or fungal infections * Seizures or history of seizures * History of another non-hematologic malignancy unless disease-free for at least 5 years * Uncontrolled intercurrent illness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Cumulative Incidence of Grade II-IV Acute GVHD up to Day 100 After Stem Cell Infusion | Day 100 | The primary outcome of this study is the cumulative incidence of grade II-IV acute GVHD up to Day 100 after stem cell infusion. Acute GHVD is graded according to the modified Glucksberg criteria (adapted from Thomas et al., NEJM ,1975, pp. 895-90), which is based on criteria by which the provider classifies acute GVHD per its objective organ staging. Acute GVHD is assessed in weekly standard of care visits post stem cell infusion and is captured in the protocol EDC upon evaluation of clinical notes up to Day 100. Data for acute GVHD organ staging and etiologies are collected in an acute GVHD separate case report form and do not include system organ class, expectedness or attribution. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage Donor Engraftment up to Day 30 Post Stem Cell Infusion | Day 30 | To assess the percentage donor engraftment up to day 30 post stem cell infusion, defined as the first of 3 consecutive days tested of documented absolute netrophil count (ANC) \>/= 500 cells/u/L |
| The Non-relapse Mortality, Progression-free and Overall Survival up to 1 Year After Stem Cell Infusion | 1 year | Progression free and overall survival by 1 year after stem cell infusion will be assessed using the method of Kaplan and Meier. Progression-free survival will be defined as the time from stem cell infusion to the time of disease progression or death from any cause. Overall survival will be defined as the time from stem cell infusion to the time to death from any cause. Patients will be censored at the time last documented alive. Cumulative incidence and Kaplan-Meier curves will be constructed as appropriate. Progression is defined per clinical presentation, not protocol specified, and vary per disease, e.g. blasts in bone marrow or peripheral blood for AML/MDS; lymphoma + on PET/CT re-staging etc. |
| The Cumulative Incidence of Chronic GVHD Requiring Systemic Immune Suppression up to 1 Year After Stem Cell Infusion | 1 year | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Velcade/Tac/MTX Drug: Bortezomib, Tacrolimus, Methotrexate
Other Names:
Velcade
Bortezomib 1.3 mg/m\^2 IV Tacrolimus 0.05 mg/kg PO bid Methotrexate 15 mg/m\^2 IV | 34 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 5 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Velcade/Tac/MTX |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants |
| Region of Enrollment United States | 34 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 34 |
| serious Total, serious adverse events | 5 / 34 |
Outcome results
Primary
The Cumulative Incidence of Grade II-IV Acute GVHD up to Day 100 After Stem Cell Infusion
The primary outcome of this study is the cumulative incidence of grade II-IV acute GVHD up to Day 100 after stem cell infusion. Acute GHVD is graded according to the modified Glucksberg criteria (adapted from Thomas et al., NEJM ,1975, pp. 895-90), which is based on criteria by which the provider classifies acute GVHD per its objective organ staging. Acute GVHD is assessed in weekly standard of care visits post stem cell infusion and is captured in the protocol EDC upon evaluation of clinical notes up to Day 100. Data for acute GVHD organ staging and etiologies are collected in an acute GVHD separate case report form and do not include system organ class, expectedness or attribution.
Time frame: Day 100
Population: One participant signed consent and was enrolled onto study, however, was immediately taken off study because it became evident that the participant needed further therapy and was not ready to proceed to transplant.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Velcade/Tac/MTX | The Cumulative Incidence of Grade II-IV Acute GVHD up to Day 100 After Stem Cell Infusion | 32 Percentage of participants |
Secondary
The Cumulative Incidence of Chronic GVHD Requiring Systemic Immune Suppression up to 1 Year After Stem Cell Infusion
Time frame: 1 year
Population: One participant signed consent and was enrolled onto study, however, was immediately taken off study because it became evident that the participant needed further therapy and was not ready to proceed to transplant.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Velcade/Tac/MTX | The Cumulative Incidence of Chronic GVHD Requiring Systemic Immune Suppression up to 1 Year After Stem Cell Infusion | 53 Percentage of participants |
Secondary
The Non-relapse Mortality, Progression-free and Overall Survival up to 1 Year After Stem Cell Infusion
Progression free and overall survival by 1 year after stem cell infusion will be assessed using the method of Kaplan and Meier. Progression-free survival will be defined as the time from stem cell infusion to the time of disease progression or death from any cause. Overall survival will be defined as the time from stem cell infusion to the time to death from any cause. Patients will be censored at the time last documented alive. Cumulative incidence and Kaplan-Meier curves will be constructed as appropriate. Progression is defined per clinical presentation, not protocol specified, and vary per disease, e.g. blasts in bone marrow or peripheral blood for AML/MDS; lymphoma + on PET/CT re-staging etc.
Time frame: 1 year
Population: One participant signed consent and was enrolled onto study, however, was immediately taken off study because it became evident that the participant needed further therapy and was not ready to proceed to transplant.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Velcade/Tac/MTX | The Non-relapse Mortality, Progression-free and Overall Survival up to 1 Year After Stem Cell Infusion | non-relapse mortality | 8.8 Percent of participants |
| Velcade/Tac/MTX | The Non-relapse Mortality, Progression-free and Overall Survival up to 1 Year After Stem Cell Infusion | progression-free survival | 85 Percent of participants |
| Velcade/Tac/MTX | The Non-relapse Mortality, Progression-free and Overall Survival up to 1 Year After Stem Cell Infusion | overall survival | 84 Percent of participants |
Secondary
The Percentage Donor Engraftment up to Day 30 Post Stem Cell Infusion
To assess the percentage donor engraftment up to day 30 post stem cell infusion, defined as the first of 3 consecutive days tested of documented absolute netrophil count (ANC) \>/= 500 cells/u/L
Time frame: Day 30
Population: One participant signed consent and was enrolled onto study, however, was immediately taken off study because it became evident that the participant needed further therapy and was not ready to proceed to transplant.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Velcade/Tac/MTX | The Percentage Donor Engraftment up to Day 30 Post Stem Cell Infusion | 94 Percentage of participants |