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

Sponsors and Collaborators:	Memorial Sloan-Kettering Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00387959

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	Drug: cyclophosphamide Drug: cyclosporine Drug: filgrastim Drug: fludarabine phosphate Drug: mycophenolate mofetil Drug: rituximab Procedure: allogeneic hematopoietic stem cell transplantation Procedure: total-body irradiation Procedure: umbilical cord blood transplantation	Phase II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma

Drug Information available for: Cyclophosphamide Filgrastim Fludarabine Fludarabine monophosphate Rituximab Cyclosporin Cyclosporine Mycophenolate Mofetil Mycophenolate mofetil hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Overall and event-free survival at 1 year after transplantation [ Designated as safety issue: No ]

Secondary Outcome Measures:

Failure of neutrophil recovery and/or donor engraftment as assessed by bone marrow biopsy [ Designated as safety issue: No ]
Acute graft-vs-host disease (GVHD) at 100 days after transplantation [ Designated as safety issue: No ]
Chronic GVHD at 100 days, 6 months, and annually after transplantation [ Designated as safety issue: No ]
Transplant-related mortality at 100 days and 180 days after transplantation [ 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 [ 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 [ Designated as safety issue: No ]
Survival after 1 year [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	July 2006
Estimated Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

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 twice 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

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

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center	Recruiting
New York, New York, United States, 10021
Contact: Juliet Barker, MBBS 212-639-3468

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Juliet Barker, MBBS

Memorial Sloan-Kettering Cancer Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Responsible Party:	Memorial Sloan-Kettering Cancer Center ( Juliet Barker )
Study ID Numbers:	CDR0000504074, MSKCC-06066
Study First Received:	October 12, 2006
Last Updated:	December 16, 2008
ClinicalTrials.gov Identifier:	NCT00387959
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Leukemia, Lymphoid
Cyclosporine
Clotrimazole
Miconazole
Lymphoma, Mantle-Cell
Lymphoma, Follicular
Lymphoma, small cleaved-cell, diffuse
Lymphoma, B-Cell, Marginal Zone
Cyclophosphamide
Cyclosporins
Lymphoma, B-Cell
Lymphoma, large-cell
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Mycophenolate mofetil

Lymphoma
Chronic lymphocytic leukemia
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Rituximab
Leukemia, B-cell, chronic
Tioconazole
Fludarabine monophosphate
Mantle cell lymphoma
Recurrence
Lymphatic Diseases
B-cell lymphomas
Fludarabine
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Neoplasms by Histologic Type
Immune System Diseases
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors

Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Antifungal Agents
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Dermatologic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009