Clinical trial NCT00946023: Optimized Donor Selection, Nonmyeloablative BMT for B-cell Lymphomas With Post-transplantation Cy and Rituximab
Official title: Nonmyeloablative BMT With Post-transplant Cyclophosphamide, Rituximab and Optimized Donor Selection for B-cell Lymphomas
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Lymphoma
B-cell Lymphoma
Non Hodgkin Lymphoma
Chronic Lymphocytic Leukemia
Keywords: lymphoma
non hodgkin lymphoma
allogeneic
bone marrow transplantation
nonmyeloablative
cyclophosphamide
rituximab
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
First posted: 2009-07-24
Enrollment: 135
Sex: ALL
Minimum age (years): 1
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-free Survival
timeFrame: 1 year post-intervention
Secondary outcomes:
measure: Progression-free Survival
timeFrame: 2 years post-intervention
measure: Overall Survival
timeFrame: 1 year post intervention
measure: Overall Survival
timeFrame: 2 years post intervention
measure: Relapse
timeFrame: 1 year post intervention
measure: Relapse
timeFrame: 2 years post intervention
measure: Non-relapse Mortality
timeFrame: 1 year post intervention
measure: Incidence of Grades II-IV Acute Graft-versus-Host-Disease (GVHD)
timeFrame: 1 year post intervention
measure: Incidence of Grades III-IV Acute GVHD
timeFrame: 1 year post intervention
measure: Incidence of Chronic GVHD
timeFrame: 1 year post intervention
measure: Engraftment
timeFrame: Day 60
measure: Graft Failure
timeFrame: Day 60
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Yvette L Kasamon, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kanakry JA, Gocke CD, Bolanos-Meade J, Gladstone DE, Swinnen LJ, Blackford AL, Fuchs EJ, Huff CA, Borrello I, Matsui WH, Brodsky RA, Rosner GL, Shanbhag S, Luznik L, Jones RJ, Ambinder RF, Kasamon YL. Phase II Study of Nonmyeloablative Allogeneic Bone Marrow Transplantation for B Cell Lymphoma with Post-Transplantation Rituximab and Donor Selection Based First on Non-HLA Factors. Biol Blood Marrow Transplant. 2015 Dec;21(12):2115-2122. doi: 10.1016/j.bbmt.2015.07.012. Epub 2015 Jul 14.