Leukemia, Mast-Cell, Mantle-cell Lymphoma
Conditions
Brief summary
To determine if rituximab administered after allogeneic transplantation decreases the incidence of chronic graft-vs-host disease (cGvHD)
Detailed description
To test if prophylactic anti-B-cell therapy (weekly rituximab) given within 60 to 90 days after allogeneic transplantation will decrease allogeneic donor B-cell immunity and possibly the incidence of chronic graft-vs-host disease (cGvHD).
Interventions
PROCEDURETotal lymphoid irradiation
Total lymphoid irradiation (TLI) administered at 80cGy for 10 days
DRUGRituximab
Rituximab 375 mg/m2 administered as an intravenous (IV) infusion once weekly for 4 doses.
DRUGAnti-thymoglobulin, rabbit (ATG, rabbit ATG)
Rabbit anti-thymoglobulin (ATG) administered from Day -11 through Day -7 (5 doses) at 1.5 mg/kg/day, for a total dose of 7.5 mg/kg.
DRUGCyclosporine
Cyclosporine (CSP) administered orally at 6.25 mg/kg twice-a-day (BID) from Day -3 until through Day +56 post-peripheral blood progenitor cell (PBPC) infusion. Dose may be adjusted to maintain a therapeutic level of cyclosporine, or in response to renal insufficiency. If at Day +56, chimerism assessment demonstrates \> 40% donor cells in the CD3+ lineage, and the patient is without evidence of GvHD, then cyclosporine taper will begin (6% reduction per week).
Mycophenylate mofetil (MMF) will be administered at 15 mg/kg po Day 0, at 5 to 10 hours after mobilized PBPC infusion is complete
DRUGFilgrastim
Filgrastim provided as needed for neutrophil support
DRUGGranisetron
Granisetron administered as an anti-nausea agent (anti-emetic) at 1 mg orally 30 to 60 minutes before TLI
DRUGSolumedrol
Solumedrol, an anti-inflammatory glucocorticoid containing methylprednisolone sodium succinate, administered at 1 mg/kg as a premedication for anti-thymoglobulin (ATG)
DRUGAcetaminophen
Acetaminophen administered orally at 650 mg 1 hour prior to infusion of PBPC
DRUGDiphenhydramine
Diphenhydramine administered by intravenous infusion at 50 mg 1 hour prior to infusion of PBPC
DRUGHydrocortisone
Hydrocortisone administered by intravenous infusion at 100 mg 1 hour prior to infusion of PBPC
Sponsors
The Leukemia and Lymphoma Society
National Cancer Institute (NCI)
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 76 Years
Healthy volunteers
No
Inclusion criteria
Recipient Inclusion Criteria: * Between 18 and 76 years of age * Chronic lymphocytic leukemia (CLL): * Unmutated IgG VH gene status * Mutated IgG VH genes (\> 2% nucleotide change compared to somatic sequence) * Complete remission benefit most from allogeneic hematopoietic stem cell transplant (HSCT). (Physicians will be encouraged to provide aggressive chemotherapy prior to nonmyeloablative transplantation.) * Mantle cell lymphoma (MCL): Transplant physicians believe subject would benefit from allogeneic HSCT. * Adequate renal (Cr \< 2.4 mg/dL) and hepatic (Bilirubin \< 3.0 mg/dL, Aspartate aminotransferase (AST) \< 100 IU) function. * Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment. * All subjects must provide written informed consent Donor Inclusion Criteria: * Genotypically or phenotypically human leukocyte antigen (HLA)-identical. * Age \< 76 unless cleared by institutional PI * Capable of giving written, informed consent. * Must consent to peripheral blood stem cell (PBSC) mobilization with G-CSF and apheresis Recipient
Exclusion criteria
* Recipient has a 9 of 10 or 10 of 10 HLA identical donor (high resolution molecular genotyping at HLA A, B, C and DrB1, and DQ) * Pregnancy * Lactating * Serious uncontrolled infection * HIV seropositivity * Hepatitis B or C seropositivity * Cardiac function: ejection fraction \< 40% or uncontrolled cardiac failure * Pulmonary: Diffusing capacity - carbon monoxide (DLCO) \< 50% predicted * Liver function abnormalities: elevation of bilirubin to ≥ 3 mg/dL and/or AST \> 100 * Renal: creatinine \> 2.4 * Karnofsky performance score ≤ 60% * Patients with poorly controlled hypertension (systolic blood pressure \> 150 or diastolic blood pressure \> 90 repeatedly). * Known life-threatening hypersensitivity to rituximab or other anti-B cell antibodies. * Inability to comply with the allogeneic transplant treatment. * Uncontrolled central nervous system (CNS) involvement with disease Donor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Chronic Graft-vs-Host Disease (cGvHD) | 4 years | The cumulative percentage of participants who develop chronic graft-vs-host disease (cGvHD). Chronic cGvHD was defined as at least one instance of a clinically-accepted marker for cGvHD (see Filipovich, et al. Biology of Blood and Marrow Transplantation. 2005;11:945-955) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Relapse | 4 years | Subjects who Relapsed following after Allogeneic HSCT |
| Mortality | Day 100 and 1 year | Number of participants who died within 100 days and within 1 year, non-relapse and associated with relapse. |
| Overall Survival | 4 years | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prophylactic Rituximab Participants to receive total lymphoid irradiation + anti-thymoglobulin (TLI + ATG) then nonmyeloablative allogeneic stem cell transplantation, with prophylactic rituximab | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | Withdrawal by subject (before treatment) | 1 |
Baseline characteristics
| Characteristic | Prophylactic Rituximab |
|---|---|
| Age, Continuous | 57 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Patient Disease characteristics CLL- Chronic Lymphocytic Leukemia | 22 participants |
| Patient Disease characteristics MCL- Mantle Cell lymphoma | 13 participants |
| Patient Disease characteristics unknown or Not Reported | 1 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 3 Participants |
| Race (NIH/OMB) White | 32 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 35 |
| serious Total, serious adverse events | 4 / 35 |
Outcome results
Primary
Chronic Graft-vs-Host Disease (cGvHD)
The cumulative percentage of participants who develop chronic graft-vs-host disease (cGvHD). Chronic cGvHD was defined as at least one instance of a clinically-accepted marker for cGvHD (see Filipovich, et al. Biology of Blood and Marrow Transplantation. 2005;11:945-955)
Time frame: 4 years
Population: 35 total participants were analyzed. No data is available for the withdrawn participant.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prophylactic Rituximab | Chronic Graft-vs-Host Disease (cGvHD) | 20 percentage of participants |
Secondary
Incidence of Relapse
Subjects who Relapsed following after Allogeneic HSCT
Time frame: 4 years
Population: 35 total participants were analyzed. No data is available for the withdrawn participant.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prophylactic Rituximab | Incidence of Relapse | 18 Participants |
p-value: 0.07Log Rank
Secondary
Mortality
Number of participants who died within 100 days and within 1 year, non-relapse and associated with relapse.
Time frame: Day 100 and 1 year
Population: 35 total participants were analyzed. No data is available for the withdrawn participant.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prophylactic Rituximab | Mortality | Mortality within 100 days, all causes | 0 Participants |
| Prophylactic Rituximab | Mortality | Nonrelapse mortality within 1 year | 1 Participants |
| Prophylactic Rituximab | Mortality | Relapse + mortality within 1 year | 2 Participants |
Secondary
Overall Survival
Time frame: 4 years
Population: 35 total participants were analyzed. No data is available for the withdrawn participant.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prophylactic Rituximab | Overall Survival | 73 Percentage of participants by disease |
| Prophylactic Rituximab (MCL Patients) | Overall Survival | 69 Percentage of participants by disease |