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

Lymphoma Clinical Trial

Official title:

Nonmyeloablative BMT With Post-transplant Cyclophosphamide, Rituximab and Optimized Donor Selection for B-cell Lymphomas

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00946023
• Other study ID #: J0941
• Secondary ID: NA_00025589
• Status: Terminated
• Phase: Phase 2
• Start date: July 2009
• Est. completion date: July 17, 2013

Study information

• Verified date: July 2018
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 135
• Est. completion date: July 17, 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• B-cell Lymphoma
• Chronic Lymphocytic Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Non Hodgkin Lymphoma

Intervention

Drug:
• Fludarabine
Days -6 through -2: 30 mg/m^2 IV daily
• Cyclophosphamide
Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily

Radiation:
• Total body irradiation
Day -1: 200 centigray (cGy) in a single fraction

Drug:
• Tacrolimus
Start on Day 5 through Day 180
• Mycophenolate Mofetil
Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
• Rituximab
Day 30 and every week after for 8 total doses: 375 mg/m^2 IV

Biological:
• Allogeneic Bone Marrow Transplant (BMT)
Day 0: Donor bone marrow infusion

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Country where clinical trial is conducted

United States, 

References & Publications (1)

Kanakry JA, Gocke CD, Bolaños-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 Mar — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival	Percentage of participants alive and without relapse or disease progression.	1 year post-intervention
Secondary	Progression-free Survival	Percentage of participants alive with and without relapse.	2 years post-intervention
Secondary	Overall Survival	Percentage of participants alive.	1 year post intervention
Secondary	Overall Survival	Percentage of participants alive.	2 years post intervention
Secondary	Relapse	Percentage of participants alive with relapse or disease progression.	1 year post intervention
Secondary	Relapse	Percentage of participants alive with relapse or disease progression.	2 years post intervention
Secondary	Non-relapse Mortality	Percentage of participants who died due to BMT-related reasons.	1 year post intervention
Secondary	Incidence of Grades II-IV Acute Graft-versus-Host-Disease (GVHD)	Percentage of participants who experienced grade II, III, or IV acute GVHD. Acute GVHD is graded using the Przepiorka criteria.	1 year post intervention
Secondary	Incidence of Grades III-IV Acute GVHD	Percentage of participants who experienced grade II, III, or IV acute GVHD. Acute GVHD is graded using the Przepiorka criteria.	1 year post intervention
Secondary	Incidence of Chronic GVHD	Percentage of participants who experienced chronic GVHD. Chronic GVHD is graded using NIH consensus criteria and Seattle criteria.	1 year post intervention
Secondary	Engraftment	Percentage of patients who engrafted neutrophils and platelets.	Day 60
Secondary	Graft Failure	Percentage of participants who failed to engraft.	Day 60