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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase

Completed

Phase 2

Conditions

Lymphoma

Leukemia

Treatments

Drug: cyclophosphamide

Drug: mycophenolate mofetil

Biological: anti-thymocyte globulin

Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation

Biological: rituximab

Drug: fludarabine phosphate

Drug: cyclosporine

Radiation: total-body irradiation

Biological: graft-versus-tumor induction therapy

Biological: filgrastim

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00425802

MSKCC-06150

06-150

Details and patient eligibility

About

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.

Enrollment

61 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

61 participants in 1 patient group

treatment

Other group

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).

Treatment: