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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00425802
• Other study ID #: 06-150
• Secondary ID: MSKCC-06150
• Status: Completed
• Phase: Phase 2
• First received: January 19, 2007
• Last updated: October 24, 2017
• Start date: November 28, 2006
• Est. completion date: October 28, 2016

Study information

• Verified date: February 2017
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: October 28, 2016
• Est. primary completion date: October 28, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma

Intervention

Biological:
• anti-thymocyte globulin

• filgrastim

• graft-versus-tumor induction therapy

• rituximab

Drug:
• cyclophosphamide

• cyclosporine

• fludarabine phosphate

• mycophenolate mofetil

Procedure:
• nonmyeloablative allogeneic hematopoietic stem cell transplantation

Radiation:
• total-body irradiation

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

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

External Links

•   Memorial Sloan Kettering Cancer Center