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Chemotherapy, Radiation Therapy, Rituximab, and Umbilical Cord Blood Transplant in Treating Patients With B-Cell Non-Hodgkin's Lymphoma

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ClinicalTrials.gov Identifier: NCT00387959
Recruitment Status : Completed
First Posted : October 13, 2006
Results First Posted : February 1, 2016
Last Update Posted : February 1, 2016
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE October 12, 2006
First Posted Date  ICMJE October 13, 2006
Results First Submitted Date  ICMJE December 22, 2015
Results First Posted Date  ICMJE February 1, 2016
Last Update Posted Date February 1, 2016
Study Start Date  ICMJE July 2006
Actual Primary Completion Date April 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 22, 2015)
Survival at 1 Year After Transplantation [ Time Frame: 1 Year after transplant ]
The number of patients survival status 1 year after transplantation
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00387959 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Chemotherapy, Radiation Therapy, Rituximab, and Umbilical Cord Blood Transplant in Treating Patients With B-Cell Non-Hodgkin's Lymphoma
Official Title  ICMJE A Non-Myeloablative Conditioning Regimen With Peri-Transplant Rituximab and the Transplantation of Unrelated Donor Umbilical Cord Blood in Patients With B Cell Lymphoid Malignancies
Brief Summary

RATIONALE: Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine, total-body irradiation, and rituximab before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem 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 cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving chemotherapy and radiation therapy together with rituximab and an umbilical cord blood transplant works in treating patients with B-cell non-Hodgkin's lymphoma.

Detailed Description

OBJECTIVES:

Primary

  • Determine the overall and event-free survival at 1 year in patients with B-cell lymphoid malignancies treated with a nonmyeloablative conditioning regimen, rituximab, and umbilical cord blood (UCB) transplantation (UCBT).

Secondary

  • Determine the speed of neutrophil and platelet recovery post allograft in these patients.
  • Determine the incidence and speed of donor-derived engraftment and contribution of each UCB unit to engraftment in these patients.
  • Determine the incidence and severity of acute graft-vs-host disease (GVHD) at 100 days in these patients.
  • Determine the incidence and severity of chronic GVHD at 1 year in these patients.
  • Determine the incidence of serious infectious complications and correlate with laboratory measurements of immune recovery in these patients.
  • Determine the response to vaccination after UCBT in these patients.
  • Determine the incidence of treatment-related mortality at 100 days 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 after UCBT in these patients.
  • Determine the performance of laboratory studies investigating double-unit biology and correlate with unit engraftment in these patients.

OUTLINE:

  • Pre-transplant rituximab therapy: Patients receive rituximab IV on days -8 or -7 and on day -4.
  • Nonmyeloablative conditioning regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and cyclophosphamide IV on day -6. Patients also undergo total-body irradiation on day -1.
  • Umbilical cord blood transplantation: Patients undergo umbilical cord blood transplantation on day 0. Patients receive filgrastim (G-CSF) IV or subcutaneously beginning on day 7 and continuing until blood counts recover.
  • Post-transplant rituximab therapy: Patients receive rituximab IV on days 7, 14, 21, and 28.
  • Graft-vs-host disease prophylaxis: Patients receive cyclosporine IV over 2-4 hours or orally twice daily on days -3 to 100, followed by a taper. Patients also receive mycophenolate mofetil IV or orally three times daily on days -3 to 45, followed by a taper.

Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Leukemia
  • Lymphoma
Intervention  ICMJE
  • Biological: filgrastim
  • Biological: rituximab
  • Drug: cyclophosphamide
  • Drug: cyclosporine
  • Drug: fludarabine phosphate
  • Drug: mycophenolate mofetil
  • Procedure: allogeneic hematopoietic stem cell transplantation
  • Procedure: umbilical cord blood transplantation
  • Radiation: total-body irradiation
Study Arms  ICMJE Experimental: Unrelated Donor Umbilical Cord Transplant
Non-Myeloablative Conditioning Regimen with Peri-Transplant Rituximab and the Transplantation of Unrelated Donor Umbilixal Cord Blood
Interventions:
  • Biological: filgrastim
  • Biological: rituximab
  • Drug: cyclophosphamide
  • Drug: cyclosporine
  • Drug: fludarabine phosphate
  • Drug: mycophenolate mofetil
  • Procedure: allogeneic hematopoietic stem cell transplantation
  • Procedure: umbilical cord blood transplantation
  • Radiation: total-body irradiation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 9, 2013)
17
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE April 2014
Actual Primary Completion Date April 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following:

    • CD20+* aggressive B-cell non-Hodgkin's lymphoma (NHL), including 1 of the following:

      • Diffuse large cell (DLC) NHL 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 (IPI) score and in second complete remission (CR) or partial remission (PR) after prior autologous stem cell transplantation
        • Failed prior autologous stem cell transplantation and in at least PR after salvage chemotherapy
      • Large cell transformation of indolent NHL/chronic lymphocytic leukemia (CLL) meeting the following criteria:

        • CR/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, as defined by p53 positivity and in first CR/PR after initial therapy
        • Relapsed disease after initial therapy and in second or third CR/PR after salvage chemotherapy
    • CD20+* indolent NHL or CLL meeting the following criteria:

      • Must be in second or subsequent progression (pre-allograft cytoreduction necessary but CR/PR not required)
      • Indolent NHL includes, but is not limited to, any of the following:

        • Follicular NHL
        • Small cell NHL
        • Marginal zone NHL NOTE: *CD20 positivity must be demonstrated within the past 12 months
  • Relapsed disease must be biopsy proven
  • Prior pre-allograft cytoreduction may have included 1 of the following:

    • Single autologous stem cell transplantation with high-dose chemotherapy conditioning, if appropriate, and no conditioning prior to transplantation
    • Two or more courses of intensive combination chemotherapy (e.g., rituximab, irinotecan hydrochloride, cetuximab, epirubicin hydrochloride [RICE]) as appropriate according to diagnosis and prior therapy

      • Heavily pre-treated CLL patients in whom further combination chemotherapy is not appropriate may receive single-agent intermediate-dose cyclophosphamide for 2-3 courses
  • No mantle cell or DLC NHL with progressive disease at allograft work-up
  • No suitable matched related or unrelated donor available
  • Two umbilical cord blood (UCB) units available meeting the following criteria:

    • Units and recipient must be ≥ 4/6 HLA-A and -B antigen and DRB1 allele matched
    • Each unit must have ≥ 1.5 x 10^7 total nucleated cells/recipient body weight

PATIENT CHARACTERISTICS:

  • Karnofsky performance score 70-100%
  • Creatinine clearance ≥ 50 mL/min
  • Bilirubin < 2.5 mg/dL
  • AST and ALT ≤ 3 times upper limit of normal (unless due to benign congenital hyperbilirubinemia)
  • Spirometry and corrected DLCO ≥ 50% normal
  • LVEF ≥ 40%
  • Albumin ≥ 2.5 g/dL
  • No active and uncontrolled infection at time of transplantation, including active infection with Aspergillus or other mold
  • No HIV positivity
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No more than 120 days since prior autologous stem cell transplantation
  • No more than 60 days since prior chemotherapy
  • No prior allogeneic transplantation
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00387959
Other Study ID Numbers  ICMJE 06-066
MSKCC-06066
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Juliet Barker, MBBS Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date December 2015

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