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Chemotherapy, Total-Body Irradiation, Rituximab, and Donor Stem Cell Transplant in Treating Patients With B-Cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia

Primary Purpose

Leukemia, Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
anti-thymocyte globulin
filgrastim
graft-versus-tumor induction therapy
rituximab
cyclophosphamide
cyclosporine
fludarabine phosphate
mycophenolate mofetil
nonmyeloablative allogeneic hematopoietic stem cell transplantation
total-body irradiation
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring noncontiguous stage II adult diffuse large cell lymphoma, recurrent adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma, B-cell chronic lymphocytic leukemia, refractory chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, noncontiguous stage II mantle cell lymphoma, recurrent mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, noncontiguous stage II small lymphocytic lymphoma, recurrent small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, noncontiguous stage II marginal zone lymphoma, recurrent marginal zone lymphoma, splenic marginal zone lymphoma, stage III marginal zone lymphoma, stage IV marginal zone lymphoma, noncontiguous stage II adult immunoblastic large cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, recurrent adult immunoblastic large cell lymphoma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following:

    • CD20-positive aggressive B-cell non-Hodgkin's lymphoma (NHL), including any of the following subtypes:

      • Diffuse large cell lymphoma*, meeting 1 of the following criteria:

        • Relapsed disease after initial therapy, but failed to mobilize or had bone marrow involvement and therefore is not suitable for an autologous stem cell transplantation
        • High-intermediate- or high-risk second-line, age-adjusted International Prognostic Index score and in second complete remission (CR) or partial remission (PR) after autologous stem cell transplantation
        • Failed prior autologous stem cell transplantation and in PR or better after salvage chemotherapy
      • Large cell transformation of indolent NHL or chronic lymphocytic leukemia (CLL), meeting the following criteria:

        • In CR or PR of the large cell component of disease after salvage chemotherapy or autologous stem cell transplantation
      • Mantle cell lymphoma*, meeting 1 of the following criteria:

        • High-risk disease (e.g., p53 positivity) and in first CR or PR after initial therapy
        • Relapsed disease after initial therapy and in second or third CR or PR after salvage chemotherapy NOTE: *No progressive disease at allograft work-up
    • CD20-positive indolent NHL (e.g., follicular lymphoma, small cell lymphoma, or marginal zone NHL) OR CLL

      • Second or subsequent progression (pre-allograft cytoreduction necessary, but CR or PR not required)
  • Relapsed disease must be biopsy-proven
  • Must have received pre-allograft salvage chemotherapy, including 1 of the following:

    • Single autologous stem cell transplantation using high-dose chemotherapy conditioning within the past 120 days
    • At least 2 courses of intensive combination chemotherapy (e.g., RICE [rituximab, ifosfamide, carboplatin, etoposide]), according to diagnosis, within the past 80 days
    • CLL patients who have received CAMPATH do not have to receive pre-allograft salvage chemotherapy
  • HLA-compatible related or unrelated donor available

    • HLA-matched ≥ 9/10 of the A, B, C, DRB1, and DQB1 loci, as tested by high resolution typing

      • One allele mismatch allowed

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 70-100%
  • Creatinine < 1.2 mg/mL OR creatinine clearance ≥ 50 mL/min
  • Bilirubin < 2.5 mg/dL
  • AST and ALT ≤ 3 times upper limit of normal (unless benign congenital hyperbilirubinemia is present)
  • Spirometry and corrected DLCO ≥ 50% of normal
  • LVEF ≥ 40%
  • Albumin ≥ 2.5 g/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No active uncontrolled infection, including active infection with Aspergillus or other mold
  • No HIV infection
  • No hepatitis B antibody or antigen positivity

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior allogeneic transplantation

Sites / Locations

  • Memorial Sloan Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

treatment

Arm Description

This is a phase 2 study of a treatment regimen consisting of a non-myeloablative (NMA) conditioning regimen incorporating low dose chemotherapy and low dose radiation as well as peri-transplant Rituximab and the transplantation of peripheral blood stem cells (PBSC) or bone marrow if PBSC collection not possible from an HLA compatible related or unrelated donor in patients with B cell lymphoid malignancies including diffuse large cell (DLC) and mantle cell non-Hodgkin's lymphoma (NHL), indolent B cell NHL, or chronic lymphocytic leukemia (CLL).

Outcomes

Primary Outcome Measures

Overall Survival at 1 Year

Secondary Outcome Measures

Time to Neutrophil Engraftment
Time to Platelet Engraftment
Incidence of Moderate to Severe Grades II to IV Graft Versus Host Disease (GVHD) at 100 Days
Incidence of Chronic GVHD at 1 Year
Immune Reconstruction/CD4+ Count at 3 Months
Response to Treatment
Immune Reconstruction/CD4+ Count at 6 Months
Immune Reconstruction/CD4+ Count at 1 Year

Full Information

First Posted
January 19, 2007
Last Updated
October 24, 2017
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00425802
Brief Title
Chemotherapy, Total-Body Irradiation, Rituximab, and Donor Stem Cell Transplant in Treating Patients With B-Cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia
Official Title
A Non-Myeloablative Conditioning Regimen With Peri-Transplant Rituximab and the Transplantation of Hematopoietic Stem Cells From HLA-Compatible Related or Unrelated Donors in Patients With B Cell Lymphoid Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
November 28, 2006 (Actual)
Primary Completion Date
October 28, 2016 (Actual)
Study Completion Date
October 28, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
RATIONALE: Giving low doses of chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Also, monoclonal antibodies, such as rituximab, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving rituximab before transplant and cyclosporine and mycophenolate mofetil after transplant may stop this from happening. PURPOSE: This phase II trial is studying the side effects and how well giving chemotherapy and radiation therapy together with rituximab and donor stem cell transplant works in treating patients with B-cell non-Hodgkin's lymphoma or chronic lymphocytic leukemia.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma
Keywords
noncontiguous stage II adult diffuse large cell lymphoma, recurrent adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma, B-cell chronic lymphocytic leukemia, refractory chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, noncontiguous stage II mantle cell lymphoma, recurrent mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, noncontiguous stage II small lymphocytic lymphoma, recurrent small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, noncontiguous stage II marginal zone lymphoma, recurrent marginal zone lymphoma, splenic marginal zone lymphoma, stage III marginal zone lymphoma, stage IV marginal zone lymphoma, noncontiguous stage II adult immunoblastic large cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, recurrent adult immunoblastic large cell lymphoma

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
treatment
Arm Type
Other
Arm Description
This is a phase 2 study of a treatment regimen consisting of a non-myeloablative (NMA) conditioning regimen incorporating low dose chemotherapy and low dose radiation as well as peri-transplant Rituximab and the transplantation of peripheral blood stem cells (PBSC) or bone marrow if PBSC collection not possible from an HLA compatible related or unrelated donor in patients with B cell lymphoid malignancies including diffuse large cell (DLC) and mantle cell non-Hodgkin's lymphoma (NHL), indolent B cell NHL, or chronic lymphocytic leukemia (CLL).
Intervention Type
Biological
Intervention Name(s)
anti-thymocyte globulin
Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Type
Biological
Intervention Name(s)
graft-versus-tumor induction therapy
Intervention Type
Biological
Intervention Name(s)
rituximab
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
cyclosporine
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Intervention Type
Drug
Intervention Name(s)
mycophenolate mofetil
Intervention Type
Procedure
Intervention Name(s)
nonmyeloablative allogeneic hematopoietic stem cell transplantation
Intervention Type
Radiation
Intervention Name(s)
total-body irradiation
Primary Outcome Measure Information:
Title
Overall Survival at 1 Year
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Time to Neutrophil Engraftment
Time Frame
2 years
Title
Time to Platelet Engraftment
Time Frame
1 year
Title
Incidence of Moderate to Severe Grades II to IV Graft Versus Host Disease (GVHD) at 100 Days
Time Frame
100 days
Title
Incidence of Chronic GVHD at 1 Year
Time Frame
1 year
Title
Immune Reconstruction/CD4+ Count at 3 Months
Time Frame
3 months
Title
Response to Treatment
Time Frame
2 years
Title
Immune Reconstruction/CD4+ Count at 6 Months
Time Frame
6 months
Title
Immune Reconstruction/CD4+ Count at 1 Year
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of 1 of the following: CD20-positive aggressive B-cell non-Hodgkin's lymphoma (NHL), including any of the following subtypes: Diffuse large cell lymphoma*, meeting 1 of the following criteria: Relapsed disease after initial therapy, but failed to mobilize or had bone marrow involvement and therefore is not suitable for an autologous stem cell transplantation High-intermediate- or high-risk second-line, age-adjusted International Prognostic Index score and in second complete remission (CR) or partial remission (PR) after autologous stem cell transplantation Failed prior autologous stem cell transplantation and in PR or better after salvage chemotherapy Large cell transformation of indolent NHL or chronic lymphocytic leukemia (CLL), meeting the following criteria: In CR or PR of the large cell component of disease after salvage chemotherapy or autologous stem cell transplantation Mantle cell lymphoma*, meeting 1 of the following criteria: High-risk disease (e.g., p53 positivity) and in first CR or PR after initial therapy Relapsed disease after initial therapy and in second or third CR or PR after salvage chemotherapy NOTE: *No progressive disease at allograft work-up CD20-positive indolent NHL (e.g., follicular lymphoma, small cell lymphoma, or marginal zone NHL) OR CLL Second or subsequent progression (pre-allograft cytoreduction necessary, but CR or PR not required) Relapsed disease must be biopsy-proven Must have received pre-allograft salvage chemotherapy, including 1 of the following: Single autologous stem cell transplantation using high-dose chemotherapy conditioning within the past 120 days At least 2 courses of intensive combination chemotherapy (e.g., RICE [rituximab, ifosfamide, carboplatin, etoposide]), according to diagnosis, within the past 80 days CLL patients who have received CAMPATH do not have to receive pre-allograft salvage chemotherapy HLA-compatible related or unrelated donor available HLA-matched ≥ 9/10 of the A, B, C, DRB1, and DQB1 loci, as tested by high resolution typing One allele mismatch allowed PATIENT CHARACTERISTICS: Karnofsky performance status 70-100% Creatinine < 1.2 mg/mL OR creatinine clearance ≥ 50 mL/min Bilirubin < 2.5 mg/dL AST and ALT ≤ 3 times upper limit of normal (unless benign congenital hyperbilirubinemia is present) Spirometry and corrected DLCO ≥ 50% of normal LVEF ≥ 40% Albumin ≥ 2.5 g/dL Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active uncontrolled infection, including active infection with Aspergillus or other mold No HIV infection No hepatitis B antibody or antigen positivity PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior allogeneic transplantation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hugo R. Castro-Malaspina, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Juliet Barker, MBBS
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Craig Moskowitz, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24534109
Citation
Sauter CS, Lechner L, Scordo M, Zheng J, Devlin SM, Fleming SE, Castro-Malaspina H, Moskowitz CH. Pretransplantation fluorine-18-deoxyglucose--positron emission tomography scan lacks prognostic value in chemosensitive B cell non-hodgkin lymphoma patients undergoing nonmyeloablative allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2014 Jun;20(6):881-4. doi: 10.1016/j.bbmt.2014.02.009. Epub 2014 Feb 15.
Results Reference
derived
Links:
URL
https://www.mskcc.org/
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

Chemotherapy, Total-Body Irradiation, Rituximab, and Donor Stem Cell Transplant in Treating Patients With B-Cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia

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