search
Back to results

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

Primary Purpose

Lymphoma, B-cell Lymphoma, Non Hodgkin Lymphoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Fludarabine
Cyclophosphamide
Total body irradiation
Tacrolimus
Mycophenolate Mofetil
Rituximab
Allogeneic Bone Marrow Transplant (BMT)
Sponsored by
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring lymphoma, non hodgkin lymphoma, allogeneic, bone marrow transplantation, nonmyeloablative, cyclophosphamide, rituximab

Eligibility Criteria

1 Year - 75 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Transplant

Arm Description

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.

Outcomes

Primary Outcome Measures

Progression-free Survival
Percentage of participants alive and without relapse or disease progression.

Secondary Outcome Measures

Progression-free Survival
Percentage of participants alive with and without relapse.
Overall Survival
Percentage of participants alive.
Overall Survival
Percentage of participants alive.
Relapse
Percentage of participants alive with relapse or disease progression.
Relapse
Percentage of participants alive with relapse or disease progression.
Non-relapse Mortality
Percentage of participants who died due to BMT-related reasons.
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.
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.
Incidence of Chronic GVHD
Percentage of participants who experienced chronic GVHD. Chronic GVHD is graded using NIH consensus criteria and Seattle criteria.
Engraftment
Percentage of patients who engrafted neutrophils and platelets.
Graft Failure
Percentage of participants who failed to engraft.

Full Information

First Posted
July 21, 2009
Last Updated
July 26, 2018
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
search

1. Study Identification

Unique Protocol Identification Number
NCT00946023
Brief Title
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

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Terminated
Why Stopped
Funding was unavailable to complete the study as originally planned.
Study Start Date
July 2009 (Actual)
Primary Completion Date
July 2013 (Actual)
Study Completion Date
July 17, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, B-cell Lymphoma, Non Hodgkin Lymphoma, Chronic Lymphocytic Leukemia
Keywords
lymphoma, non hodgkin lymphoma, allogeneic, bone marrow transplantation, nonmyeloablative, cyclophosphamide, rituximab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
135 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Transplant
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludara
Intervention Description
Days -6 through -2: 30 mg/m^2 IV daily
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan, CTX, Cy
Intervention Description
Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily
Intervention Type
Radiation
Intervention Name(s)
Total body irradiation
Other Intervention Name(s)
TBI
Intervention Description
Day -1: 200 centigray (cGy) in a single fraction
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Other Intervention Name(s)
FK-506, FK506, Prograf
Intervention Description
Start on Day 5 through Day 180
Intervention Type
Drug
Intervention Name(s)
Mycophenolate Mofetil
Other Intervention Name(s)
MMF, CellCept
Intervention Description
Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
Day 30 and every week after for 8 total doses: 375 mg/m^2 IV
Intervention Type
Biological
Intervention Name(s)
Allogeneic Bone Marrow Transplant (BMT)
Intervention Description
Day 0: Donor bone marrow infusion
Primary Outcome Measure Information:
Title
Progression-free Survival
Description
Percentage of participants alive and without relapse or disease progression.
Time Frame
1 year post-intervention
Secondary Outcome Measure Information:
Title
Progression-free Survival
Description
Percentage of participants alive with and without relapse.
Time Frame
2 years post-intervention
Title
Overall Survival
Description
Percentage of participants alive.
Time Frame
1 year post intervention
Title
Overall Survival
Description
Percentage of participants alive.
Time Frame
2 years post intervention
Title
Relapse
Description
Percentage of participants alive with relapse or disease progression.
Time Frame
1 year post intervention
Title
Relapse
Description
Percentage of participants alive with relapse or disease progression.
Time Frame
2 years post intervention
Title
Non-relapse Mortality
Description
Percentage of participants who died due to BMT-related reasons.
Time Frame
1 year post intervention
Title
Incidence of Grades II-IV Acute Graft-versus-Host-Disease (GVHD)
Description
Percentage of participants who experienced grade II, III, or IV acute GVHD. Acute GVHD is graded using the Przepiorka criteria.
Time Frame
1 year post intervention
Title
Incidence of Grades III-IV Acute GVHD
Description
Percentage of participants who experienced grade II, III, or IV acute GVHD. Acute GVHD is graded using the Przepiorka criteria.
Time Frame
1 year post intervention
Title
Incidence of Chronic GVHD
Description
Percentage of participants who experienced chronic GVHD. Chronic GVHD is graded using NIH consensus criteria and Seattle criteria.
Time Frame
1 year post intervention
Title
Engraftment
Description
Percentage of patients who engrafted neutrophils and platelets.
Time Frame
Day 60
Title
Graft Failure
Description
Percentage of participants who failed to engraft.
Time Frame
Day 60

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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): Follicular grade 1 or 2 lymphoma Follicular lymphoma not otherwise specified Marginal zone (or MALT) lymphoma Lymphoplasmacytic lymphoma / Waldenstrom's macroglobulinemia Hairy cell leukemia Small lymphocytic lymphoma / chronic lymphocytic leukemia (SLL/CLL) Low grade B-cell lymphoma, unspecified 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: Follicular grade 3 lymphoma Histoconversion of low-grade B-cell lymphoma (including SLL/CLL) to aggressive B-cell non-Hodgkin's lymphoma Mantle cell lymphoma Diffuse large B-cell lymphoma (excluding primary CNS [central nervous system] lymphoma) "Gray zone" or composite lymphomas with combined features of primary mediastinal large B-cell and Hodgkin's lymphoma Burkitt's lymphoma/leukemia 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yvette L Kasamon, MD
Organizational Affiliation
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
26183076
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.
Results Reference
result

Learn more about this trial

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

We'll reach out to this number within 24 hrs