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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00425802
First received: January 19, 2007
Last updated: April 23, 2014
Last verified: April 2014

January 19, 2007
April 23, 2014
November 2006
November 2015   (final data collection date for primary outcome measure)
Overall and event-free survival at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Overall and event-free survival at 1 year
Complete list of historical versions of study NCT00425802 on ClinicalTrials.gov Archive Site
  • Speed of neutrophil and platelet recovery [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Incidence and speed of donor-derived engraftment [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Incidence and severity of acute graft versus host disease (GVHD) at 100 days [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Incidence and severity of chronic GVHD at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Correlation of incidence of serious infectious complications with immune recovery [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Response to treatment [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Incidence of transplant-related mortality at 100 and 180 days [ Time Frame: 180 days ] [ Designated as safety issue: No ]
  • Incidence of malignant relapse or disease progression at 1 and 2 years [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Probabilities of overall and event-free survival at 2 years [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Speed of neutrophil and platelet recovery
  • Incidence and speed of donor-derived engraftment
  • Incidence and severity of acute graft versus host disease (GVHD) at 100 days
  • Incidence and severity of chronic GVHD at 1 year
  • Correlation of incidence of serious infectious complications with immune recovery
  • Response to treatment
  • Incidence of transplant-related mortality at 100 and 180 days
  • Incidence of malignant relapse or disease progression at 1 and 2 years
  • Probabilities of overall and event-free survival at 2 years
Not Provided
Not Provided
 
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

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.

OBJECTIVES:

Primary

  • Determine the overall and event-free survival at 1 year in patients with B-cell non-Hodgkin's lymphoma or chronic lymphocytic leukemia treated with a nonmyeloablative conditioning regimen, rituximab, and allogeneic hematopoietic stem cell transplantation.

Secondary

  • Determine the speed of neutrophil and platelet recovery in patients treated with this regimen.
  • Determine the incidence and speed of donor-derived engraftment in these patients.
  • Determine the incidence and severity of acute graft versus host disease (GVHD) at 100 days in patients treated with this regimen.
  • Determine the incidence and severity of chronic GVHD at 1 year in patients treated with this regimen.
  • Correlate the incidence of serious infectious complications with immune recovery in patients treated with this regimen.
  • Determine the response in patients treated with this regimen.
  • Determine the incidence of transplant-related mortality at 100 and 180 days in these patients.
  • Determine the incidence of malignant relapse or disease progression at 1 and 2 years in these patients.
  • Determine the probabilities of overall and event-free survival at 2 years in patients treated with this regimen.

OUTLINE: Patients are stratified according to donor type (HLA-matched related vs HLA-matched unrelated or single HLA allele-disparate related or unrelated).

  • Rituximab therapy: Patients receive rituximab IV on day -8 or -7 and on days 21, 28, 35, and 42 (+ or - 2 days).
  • Nonmyeloablative conditioning: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2, cyclophosphamide IV on day -6, and anti-thymocyte globulin (ATG)* IV over 4-6 hours on days -3 and/or -2. Patients undergo total-body irradiation on day -1.

NOTE: *Patients with HLA-matched sibling donors do not receive ATG.

  • Allogeneic hematopoietic stem cell transplantation (HSCT): Patients undergo filgrastim (G-CSF)-mobilized allogeneic HSCT on day 0. Patients receive filgrastim (G-CSF) IV or subcutaneously beginning on day 7 and continuing until blood counts recover.
  • Graft versus host disease prophylaxis: Patients receive cyclosporine IV over 2-4 hours or orally twice daily on days -3 to 100 followed by a taper and mycophenolate mofetil IV or orally twice daily on days -3 to 45 followed by a taper, in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3-6 months for 2 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Leukemia
  • Lymphoma
  • Biological: anti-thymocyte globulin
  • Biological: filgrastim
  • Biological: graft-versus-tumor induction therapy
  • Biological: rituximab
  • Drug: cyclophosphamide
  • Drug: cyclosporine
  • Drug: fludarabine phosphate
  • Drug: mycophenolate mofetil
  • Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
  • Radiation: total-body irradiation
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).
Interventions:
  • Biological: anti-thymocyte globulin
  • Biological: filgrastim
  • Biological: graft-versus-tumor induction therapy
  • Biological: rituximab
  • Drug: cyclophosphamide
  • Drug: cyclosporine
  • Drug: fludarabine phosphate
  • Drug: mycophenolate mofetil
  • Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
  • Radiation: total-body irradiation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
61
November 2015
November 2015   (final data collection date for primary outcome measure)

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
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00425802
06-150, MSKCC-06150
Not Provided
Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Hugo R. Castro-Malaspina, MD Memorial Sloan-Kettering Cancer Center
Principal Investigator: Juliet Barker, MBBS Memorial Sloan-Kettering Cancer Center
Principal Investigator: Craig Moskowitz, MD Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP