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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00387959
First received: October 12, 2006
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Leukemia
Lymphoma
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
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Overall and event-free survival at 1 year after transplantation [ Time Frame: 1 Year after transplant ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Failure of neutrophil recovery and/or donor engraftment as assessed by bone marrow biopsy [ Time Frame: 45 days after transplant ] [ Designated as safety issue: No ]
  • Acute graft-vs-host disease (GVHD) at 100 days after transplantation [ Time Frame: 100 days after transplant ] [ Designated as safety issue: No ]
  • Chronic GVHD at 100 days, 6 months, and annually after transplantation [ Time Frame: 100 days, 6 months, and annually after transplantation ] [ Designated as safety issue: No ]
  • Transplant-related mortality at 100 days and 180 days after transplantation [ Time Frame: 100 days and 180 days after transplant ] [ Designated as safety issue: No ]
  • Disease relapse or progression as assessed by radiologic studies, flow cytometric analysis or molecular studies of the marrow and/or peripheral blood, and/or biopsy of lymph nodes or other sites [ Time Frame: 1 and 2 years after transplant ] [ Designated as safety issue: No ]
  • Non-Hodgkin's lymphoma (NHL) relapse or disease progression as assessed by Cheson criteria with modification for positron emission tomography (PET) assessment and for molecular complete remission [ Time Frame: 1 and 2 years after transplant ] [ Designated as safety issue: No ]
  • Survival after 1 year [ Time Frame: 1 Year after transplant ] [ Designated as safety issue: No ]

Enrollment: 17
Study Start Date: July 2006
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Unrelated Donor Umbilical Cord Transplant
Non-Myeloablative Conditioning Regimen with Peri-Transplant Rituximab and the Transplantation of Unrelated Donor Umbilixal Cord Blood
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00387959

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Juliet Barker, MBBS Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00387959     History of Changes
Other Study ID Numbers: 06-066, MSKCC-06066
Study First Received: October 12, 2006
Last Updated: April 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
recurrent mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle 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
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
recurrent marginal zone lymphoma
recurrent adult diffuse small cleaved cell lymphoma
splenic marginal zone lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
noncontiguous stage II marginal zone lymphoma
stage III marginal zone lymphoma
stage IV marginal zone lymphoma

Additional relevant MeSH terms:
Leukemia
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Cyclosporins
Cyclosporine
Mycophenolate mofetil
Fludarabine phosphate
Rituximab
Fludarabine
Mycophenolic Acid
Lenograstim
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 01, 2014