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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00425802

Enrollment

Registered

2007-01-23

Start date

2006-11-28

Completion date

2016-10-28

Last updated

2017-10-31

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

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.

Interventions

BIOLOGICALanti-thymocyte globulin

BIOLOGICALfilgrastim

BIOLOGICALgraft-versus-tumor induction therapy

BIOLOGICALrituximab

DRUGcyclophosphamide

DRUGcyclosporine

DRUGfludarabine phosphate

DRUGmycophenolate mofetil

PROCEDUREnonmyeloablative allogeneic hematopoietic stem cell transplantation

RADIATIONtotal-body irradiation

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame
Overall Survival at 1 Year	1 year

Secondary

Measure	Time frame
Time to Platelet Engraftment	1 year
Incidence of Moderate to Severe Grades II to IV Graft Versus Host Disease (GVHD) at 100 Days	100 days
Incidence of Chronic GVHD at 1 Year	1 year
Time to Neutrophil Engraftment	2 years
Response to Treatment	2 years
Immune Reconstruction/CD4+ Count at 6 Months	6 months
Immune Reconstruction/CD4+ Count at 1 Year	1 year
Immune Reconstruction/CD4+ Count at 3 Months	3 months

Countries

United States

Participant flow

Recruitment details

Protocol Open to Accrual 11/28/2006 Protocol Closed to Accrual 4/22/2014 Primary Completion Date 10/28/2016 Recruitment Location is the medical clinic

Participants by arm

Arm	Count
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).	61
Total	61

Arm

Count

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).

Total

Baseline characteristics

Characteristic	Treatment
Age, Continuous	54 years
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	59 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	1 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants
Race (NIH/OMB) White	59 Participants
Region of Enrollment United States	61 Participants
Sex: Female, Male Female	11 Participants
Sex: Female, Male Male	50 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	9 / 61
other Total, other adverse events	59 / 61
serious Total, serious adverse events	26 / 61