Lymphoma
Conditions
Keywords
recurrent adult Hodgkin lymphoma, recurrent small lymphocytic lymphoma, recurrent mantle cell lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse large cell lymphoma
Brief summary
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and melphalan, before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and methotrexate after transplant may stop this from happening. PURPOSE: This phase II trial is studying how well giving fludarabine together with melphalan followed by tacrolimus and methotrexate works in treating patients who are undergoing a donor stem cell transplant for relapsed lymphoma.
Detailed description
OBJECTIVES: * Determine the 1-year progression-free and overall survival rate in patients with relapsed Hodgkin's or non-Hodgkin's lymphoma after prior autologous stem cell transplantation treated with a nonmyeloablative conditioning regimen comprising fludarabine and melphalan followed by allogeneic bone marrow or peripheral blood stem cell transplantation and immunosuppression comprising tacrolimus and methotrexate. * Determine treatment-related mortality in patients treated with this regimen. * Determine the toxic effects of this regimen in these patients. * Determine engraftment of donor hematopoietic stem cells, as measured by hematopoietic recovery and donor-derived hematopoiesis (determined by T cell and neutrophil specific chimerism) at 2, 3, 6, and 12 months, in patients treated with this regimen. * Determine the incidence of acute and chronic graft-versus-host disease in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients are stratified according to diagnosis (Hodgkin's lymphoma vs non-Hodgkin's lymphoma). Patients receive fludarabine IV over 1 hour on days -6 to -2 and melphalan IV over 15-20 minutes on days -3 and -2. Patients undergo allogeneic peripheral blood stem cell or bone marrow transplantation on day 0. Patients receive oral tacrolimus twice daily beginning on day -3 and continuing until day 100 followed by a taper to day 180. Patients also receive methotrexate IV on days 1, 3, and 7. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study transplantation, patients are followed at 1 and 3 months, 1 year, and then annually for up to 4 years. PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within 2 years.
Interventions
DRUGfludarabine phosphate
30 mg/m\^2 on days -6 to -2 (2-6 days before transplant).
DRUGmelphalan
70 mg/m\^2 on days -3 and -2 (2-3 days before transplant).
DRUGmethotrexate
5 mg/m\^2 on days 1, 3, and 7 post-transplant.
DRUGtacrolimus
0.03 mg/kg bid on days -3 to 100 post-transplant.
PROCEDUREallogeneic bone marrow transplantation
if donor bone marrow stem cells are harvested
PROCEDUREperipheral blood stem cell transplantation
if donor peripheral blood stem cells are harvested
Sponsors
National Cancer Institute (NCI)
SWOG Cancer Research Network
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
DISEASE CHARACTERISTICS: * Diagnosis of lymphoma of 1 of the following types: * Diffuse large B-cell lymphoma * Follicular lymphoma * Grades 1, 2, or 3 * Primary mediastinal lymphoma * Mantle cell lymphoma * Small lymphocytic lymphoma * Hodgkin's lymphoma * Transformed lymphoma * Relapsed after prior autologous bone marrow transplantation (BMT) * More than 180 days post BMT * Received ≥ 1 course of chemotherapy after BMT relapse * Achieved a complete response OR a partial response to chemotherapy * Largest residual tumor dimension ≤ 2 cm * No clinical or laboratory evidence of CNS involvement by lymphoma * HLA-identical donor available, meeting 1 of the following criteria: * Sibling donor with 5/6 or 6/6 alleles matching by genotyping * No monozygotic identical twins * Unrelated donor with 10/10 alleles matching by genotyping PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Zubrod 0-2 Life expectancy * Not specified Hematopoietic * Not specified Hepatic * Not specified Renal * Not specified Cardiovascular * LVEF ≥ 40% by MUGA or 2-D echocardiogram (2-D ECHO) * No significant cardiac abnormalities by MUGA or 2-D ECHO * No uncompensated coronary artery disease by ECG or physical exam * None of the following within the past 6 months: * Myocardial infarction * Unstable angina * Uncontrolled atrial fibrillation * None of the following within the past 3 months: * Severe peripheral vascular disease * Venous stasis ulcers * Deep venous or arterial thrombosis * No uncontrolled hypertension Pulmonary * DLCO (corrected) and total lung capacity ≥ 40% of predicted * No requirement for continuous supplemental oxygen Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * HIV negative * No AIDS * No active bacterial, viral, or fungal infection * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * No history of uncontrolled seizures * No diabetic ulcers within the past 3 months PRIOR CONCURRENT THERAPY: Biologic therapy * See Disease Characteristics * No more than 1 prior bone marrow transplantation Chemotherapy * See Disease Characteristics * More than 21 days since prior chemotherapy and recovered Endocrine therapy * Not specified Radiotherapy * More than 4 weeks since prior radiotherapy Surgery * More than 4 weeks since prior major surgery except placement of a venous access device
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | 1, 3, and 12 months after protocol treatment, then every 3 months for 1 year, every 6 months for year 2, then annually thereafter until 5 years after registration | PFS rate at 1 year. |
| Overall Survival | 1, 3, and 12 months after protocol treatment, then every 3 months for 1 year, every 6 months for year 2, then annually thereafter until 5 years after registration | OS rate at 1 year. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nonmyeloablative Allogeneic Stem Cell Transplant Patients are given fludarabine 30 mg/m\^2 on days -6 to -2 and melphalan 70 mg/m\^2 on days -3 and -2, then transplanted with donor peripheral blood stem cells or harvested bone marrow stem cells on day 0. Patients are then given post-transplant immunosuppression consisting of tacrolimus 0.06 mg/kg/day on days -3 to 100 and methotrexate 5 mg/m\^2 on days 1, 3, and 7. | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Nonmyeloablative Allogeneic Stem Cell Transplant |
|---|---|
| Age Continuous | 47.2 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| 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 | 1 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Overall Survival
OS rate at 1 year.
Time frame: 1, 3, and 12 months after protocol treatment, then every 3 months for 1 year, every 6 months for year 2, then annually thereafter until 5 years after registration
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nonmyeloablative Allogeneic Stem Cell Transplant | Overall Survival | 1 participants |
Primary
Progression-free Survival
PFS rate at 1 year.
Time frame: 1, 3, and 12 months after protocol treatment, then every 3 months for 1 year, every 6 months for year 2, then annually thereafter until 5 years after registration
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nonmyeloablative Allogeneic Stem Cell Transplant | Progression-free Survival | 1 participants |