Optimized Donor Selection, Nonmyeloablative BMT for B-cell Lymphomas With Post-transplantation Cy and Rituximab

NCT ID: NCT00946023

Last Updated: 2018-08-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 135 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2013-07-17

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.

Conditions

Lymphoma; B-cell Lymphoma; Non Hodgkin Lymphoma; Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Transplant

Non-myeloablative allogeneic bone marrow transplant (BMT) with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD (graft vs host disease) prophylaxis. Rituximab will be given as post-transplant maintenance.

Group Type: EXPERIMENTAL

Fludarabine

Intervention Type: DRUG

Days -6 through -2: 30 mg/m\^2 IV daily

Cyclophosphamide

Intervention Type: DRUG

Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily

Total body irradiation

Intervention Type: RADIATION

Day -1: 200 centigray (cGy) in a single fraction

Tacrolimus

Intervention Type: DRUG

Start on Day 5 through Day 180

Mycophenolate Mofetil

Intervention Type: DRUG

Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)

Rituximab

Intervention Type: DRUG

Day 30 and every week after for 8 total doses: 375 mg/m\^2 IV

Allogeneic Bone Marrow Transplant (BMT)

Intervention Type: BIOLOGICAL

Day 0: Donor bone marrow infusion

Interventions

Fludarabine

Days -6 through -2: 30 mg/m\^2 IV daily

Intervention Type: DRUG

Cyclophosphamide

Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily

Intervention Type: DRUG

Total body irradiation

Day -1: 200 centigray (cGy) in a single fraction

Intervention Type: RADIATION

Tacrolimus

Start on Day 5 through Day 180

Intervention Type: DRUG

Mycophenolate Mofetil

Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)

Intervention Type: DRUG

Rituximab

Day 30 and every week after for 8 total doses: 375 mg/m\^2 IV

Intervention Type: DRUG

Allogeneic Bone Marrow Transplant (BMT)

Day 0: Donor bone marrow infusion

Intervention Type: BIOLOGICAL

Other Intervention Names

Fludara; Cytoxan; CTX; Cy; TBI; FK-506; FK506; Prograf; MMF; CellCept; Rituxan

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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yvette L Kasamon, MD

Role: PRINCIPAL_INVESTIGATOR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 26183076 (View on PubMed)

Other Identifiers

NA_00025589

Identifier Type: OTHER

Identifier Source: secondary_id

J0941

Identifier Type: -

Identifier Source: org_study_id