Combination Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Patients With Mantle Cell Lymphoma

This study has been terminated.
(Poor accrual)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00006747
First received: December 6, 2000
Last updated: September 25, 2013
Last verified: September 2013
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by donor peripheral stem cell transplantation in treating patients who have mantle cell lymphoma.


Condition Intervention Phase
Graft Versus Host Disease
Lymphoma
Drug: ara-C
Drug: melphalan
Drug: Etoposide
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Stem Cell Transplantation for Mantle Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Progression free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 4
Study Start Date: November 2000
Primary Completion Date: January 2003 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: ara-C
    200 mg/sq m /day IV days -5 thru -2
    Drug: melphalan
    140 mg/sq m IV on day -1
    Drug: Etoposide
    200 mg/sq m IV days -5 thru -2
Detailed Description:

OBJECTIVES:

  • Determine the long term disease-free survival of patients with mantle cell lymphoma treated with etoposide, carmustine, melphalan, and cytarabine followed by allogeneic peripheral blood stem cell transplantation.
  • Determine the incidence of molecular remissions in these patients treated with this regimen.
  • Correlate the persistence of minimal residual disease with clinical outcome in these patients treated with this regimen.
  • Determine the effect of donor lymphocytes in patients with progressive disease after treatment with this regimen.

OUTLINE: This is a multicenter study.

Patients receive carmustine IV over 2 hours on day -6; etoposide IV over 3 hours and cytarabine IV over 1 hour every 12 hours on days -5 to -2 for a total of 8 doses; and melphalan IV over 20-30 minutes on day -1. Patients undergo allogeneic peripheral blood stem cell (PBSC) transplantation on day 0. Patients also receive tacrolimus IV continuously over 24 hours beginning on day -2 and then orally twice daily until day 120 and methotrexate IV over 30 minutes on days 1, 3, and 6 as graft-versus-host disease (GVHD) prophylaxis. Patients receive sargramostim (GM-CSF) IV or subcutaneously daily beginning on day 7 and continuing until blood counts recover.

Patients with no active GVHD who have persistent disease on day 150 or progressive disease at any time after PBSC transplantation receive donor lymphocytes IV over 2 hours. Patients may receive additional donor lymphocytes at least 8 weeks later if disease persists.

Patients are followed at 6 and 12 months posttransplantation and then annually for 4 years.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 3.5 years.

  Eligibility

Ages Eligible for Study:   up to 59 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed mantle cell lymphoma of any stage with at least 1 of the following:

    • Immunophenotype with expression of CD5 and CD19 and absence of CD23
    • Cytogenetic analysis with presence of t(11;14)
    • Overexpression of cyclin D1
    • Rearrangement of BCL1 gene
  • Bone marrow biopsy required

    • No needle or core biopsy as sole means of diagnosis
  • First remission allowed if at least 1 of the following poor prognostic characteristics present:

    • International Prognostic Index (IPI) score higher than 1 defined by the following risk factors:

      • Performance status higher than 1
      • Elevated LDH
      • Presence of more than 1 extranodal site
      • Stage III or IV disease
    • Blastic variant of mantle cell lymphoma*
    • Complex karyotypes (i.e., cytogenetic abnormalities different from or in addition to t(11;14)*
    • Proliferative index more than 10%*
    • Presence of p53 mutations NOTE: *Regardless of IPI score
  • Failure of initial therapy with anthracycline-containing regimen allowed

    • Failure to achieve clinical complete remission after initial therapy OR
    • Recurrent disease after initial therapy
  • HLA matched (6/6) sibling donor by serologic typing (A, B, or DR)

    • Any age
    • No syngeneic (identical twin) donor
  • No active CNS lymphoma

PATIENT CHARACTERISTICS:

Age:

  • Under 60

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

  • Bilirubin less than 2 mg/dL
  • AST and ALT no greater than 3 times upper limit of normal

Renal:

  • Creatinine less than 2 mg/dL

Pulmonary:

  • DLCO at least 40%
  • No symptomatic pulmonary disease

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior bone marrow transplantation

Chemotherapy:

  • See Disease Characteristics
  • No more than 2 prior chemotherapy regimens
  • No other concurrent chemotherapy

Endocrine therapy:

  • No concurrent hormonal therapy

Radiotherapy:

  • No concurrent radiotherapy to bulky sites

Surgery:

  • See Disease Characteristics
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00006747

  Show 48 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Investigators
Study Chair: Koen Van Besien, MD University of Chicago
  More Information

No publications provided

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00006747     History of Changes
Other Study ID Numbers: CDR0000068324, U10CA031946, CLB-59908
Study First Received: December 6, 2000
Last Updated: September 25, 2013
Health Authority: United States: Federal Government

Keywords provided by Alliance for Clinical Trials in Oncology:
graft versus host disease
stage I mantle cell lymphoma
contiguous stage II mantle cell lymphoma
noncontiguous stage II mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
recurrent mantle cell lymphoma

Additional relevant MeSH terms:
Graft vs Host Disease
Lymphoma
Lymphoma, Mantle-Cell
Immune System Diseases
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Lymphoma, Non-Hodgkin
Etoposide
Melphalan
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 15, 2014