Optimized Donor Selection, Nonmyeloablative BMT for B-cell Lymphomas With Post-transplantation Cy and Rituximab
| Status: | Terminated |
|---|---|
| Conditions: | Blood Cancer, Lymphoma |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 1 - 75 |
| Updated: | 8/29/2018 |
| Start Date: | July 2009 |
| End Date: | July 17, 2013 |
Nonmyeloablative BMT With Post-transplant Cyclophosphamide, Rituximab and Optimized Donor Selection for B-cell Lymphomas
This phase II trial is studying how well giving fludarabine and cyclophosphamide together
with total-body irradiation and rituximab works in treating patients with B-cell lymphoma or
chronic lymphocytic leukemia who are undergoing an allogeneic (donor) bone marrow transplant.
The type of bone marrow transplant is a less intensive or "mini" transplant using a relative
as the bone marrow donor. The donated bone marrow stem cells may replace the patient's immune
system cells and help destroy any remaining cancer (graft-versus-tumor effect). Patients
undergoing this type of transplant often have more than one relative who could be a donor.
The trial is also studying a new way of choosing amongst possible donors which might improve
how the rituximab works.
with total-body irradiation and rituximab works in treating patients with B-cell lymphoma or
chronic lymphocytic leukemia who are undergoing an allogeneic (donor) bone marrow transplant.
The type of bone marrow transplant is a less intensive or "mini" transplant using a relative
as the bone marrow donor. The donated bone marrow stem cells may replace the patient's immune
system cells and help destroy any remaining cancer (graft-versus-tumor effect). Patients
undergoing this type of transplant often have more than one relative who could be a donor.
The trial is also studying a new way of choosing amongst possible donors which might improve
how the rituximab works.
This phase II for relapsed or refractory B-cell malignancies builds on the platform of
nonmyeloablative, related-donor, HLA (human leukocyte antigen)-matched or HLA-haploidentical
BMT with post-transplantation high-dose cyclosphosphamide administered for prophylaxis of
graft-versus-host disease and graft rejection. Rituximab is added to the transplant regimen
with the goal of augmenting anti-tumor activity. In patients with B-cell lymphomas, specific
polymorphisms in the immunoglobulin Fc receptor have been associated with greater sensitivity
to rituximab or rituximab-based therapies, translating in some series into higher response
rates and improved progression-free survival. This raises the possibility of selecting donors
who carry this permissive polymorphism. This trial identifies and selects donors who have the
favorable polymorphism at FcgammaR3A-158, thereby potentially conferring greater sensitivity
to rituximab in the host after BMT.
nonmyeloablative, related-donor, HLA (human leukocyte antigen)-matched or HLA-haploidentical
BMT with post-transplantation high-dose cyclosphosphamide administered for prophylaxis of
graft-versus-host disease and graft rejection. Rituximab is added to the transplant regimen
with the goal of augmenting anti-tumor activity. In patients with B-cell lymphomas, specific
polymorphisms in the immunoglobulin Fc receptor have been associated with greater sensitivity
to rituximab or rituximab-based therapies, translating in some series into higher response
rates and improved progression-free survival. This raises the possibility of selecting donors
who carry this permissive polymorphism. This trial identifies and selects donors who have the
favorable polymorphism at FcgammaR3A-158, thereby potentially conferring greater sensitivity
to rituximab in the host after BMT.
Inclusion Criteria:
- Poor-risk CD20+, B-cell lymphoma, as follows:
- Low grade B-cell lymphoma that has failed at least two prior therapies (excluding
single agent rituximab), or undergone histologic conversion (if histologic
conversion, PR or CR is required):
1. Follicular grade 1 or 2 lymphoma
2. Follicular lymphoma not otherwise specified
3. Marginal zone (or MALT) lymphoma
4. Lymphoplasmacytic lymphoma / Waldenstrom's macroglobulinemia
5. Hairy cell leukemia
6. Small lymphocytic lymphoma / chronic lymphocytic leukemia (SLL/CLL)
7. Low grade B-cell lymphoma, unspecified
8. Nodular lymphocyte-predominant Hodgkin lymphoma
- Poor-risk small lymphocytic lymphoma or chronic lymphocytic leukemia, defined by a 17p
deletion, 11q deletion, or histologic conversion (if histologic conversion, PR or CR
is required)
- Aggressive B-cell non-Hodgkin's lymphoma that has failed at least one prior regimen of
multiagent chemotherapy, is in PR (partial remission) or CR (complete remission), and
patient is either ineligible for autologous hematopoietic BMT or autologous BMT is not
recommended:
1. Follicular grade 3 lymphoma
2. Histoconversion of low-grade B-cell lymphoma (including SLL/CLL) to aggressive
B-cell non-Hodgkin's lymphoma
3. Mantle cell lymphoma
4. Diffuse large B-cell lymphoma (excluding primary CNS [central nervous system]
lymphoma)
5. "Gray zone" or composite lymphomas with combined features of primary mediastinal
large B-cell and Hodgkin's lymphoma
6. Burkitt's lymphoma/leukemia
7. Atypical Burkitt's lymphoma/leukemia (high grade B-cell lymphoma, unclassified,
including that with features intermediate between Burkitt's and diffuse large
B-cell lymphoma)
- Must have a related donor who is at least HLA haploidentical
- Any previous BMT must have occurred at least 3 months prior
- Left ventricular ejection fraction at least 35%
- Bilirubin no more than 3.0 mg/dL (unless due to Gilbert's syndrome), and ALT (alanine
aminotransferase) and AST (aspartate aminotransferase) no more than 5 x upper limit of
normal
- FEV1 (forced expiratory volume in one second) and FVC (forced vital capacity) at least
40% of predicted
- Absence of uncontrolled infection
Exclusion Criteria:
- More than 20% involvement of bone marrow by chronic lymphocytic leukemia
- Active central nervous system lymphoma
- ECOG (Eastern Cooperative Oncology Group) performance status greater than 1 (2,3, and
4)
- HIV positive
- Pregnant or breastfeeding
We found this trial at
1
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Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins The name Johns Hopkins has become synonymous...
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