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

NCT ID: NCT00425802

Last Updated: 2017-10-31

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

61 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-11-28

Study Completion Date

2016-10-28

Brief Summary

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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.

Detailed Description

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Conditions

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Leukemia Lymphoma

Keywords

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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treatment

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).

Group Type OTHER

anti-thymocyte globulin

Intervention Type BIOLOGICAL

filgrastim

Intervention Type BIOLOGICAL

graft-versus-tumor induction therapy

Intervention Type BIOLOGICAL

rituximab

Intervention Type BIOLOGICAL

cyclophosphamide

Intervention Type DRUG

cyclosporine

Intervention Type DRUG

fludarabine phosphate

Intervention Type DRUG

mycophenolate mofetil

Intervention Type DRUG

nonmyeloablative allogeneic hematopoietic stem cell transplantation

Intervention Type PROCEDURE

total-body irradiation

Intervention Type RADIATION

Interventions

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anti-thymocyte globulin

Intervention Type BIOLOGICAL

filgrastim

Intervention Type BIOLOGICAL

graft-versus-tumor induction therapy

Intervention Type BIOLOGICAL

rituximab

Intervention Type BIOLOGICAL

cyclophosphamide

Intervention Type DRUG

cyclosporine

Intervention Type DRUG

fludarabine phosphate

Intervention Type DRUG

mycophenolate mofetil

Intervention Type DRUG

nonmyeloablative allogeneic hematopoietic stem cell transplantation

Intervention Type PROCEDURE

total-body irradiation

Intervention Type RADIATION

Eligibility Criteria

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Inclusion 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hugo R. Castro-Malaspina, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Juliet Barker, MBBS

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Craig Moskowitz, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

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Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 24534109 (View on PubMed)

Related Links

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https://www.mskcc.org/

Memorial Sloan Kettering Cancer Center

Other Identifiers

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MSKCC-06150

Identifier Type: -

Identifier Source: secondary_id

06-150

Identifier Type: -

Identifier Source: org_study_id