Clinical trial NCT00006747: Combination Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Patients With Mantle Cell Lymphoma
Official title: Allogeneic Stem Cell Transplantation for Mantle Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Graft Versus Host Disease
Lymphoma
Keywords: 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
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 4
Sex: ALL
Maximum age (years): 59
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 1. Documentation of Disease

   1. Histologically documented mantle cell lymphoma of any stage (needle or core biopsy is not acceptable as the sole means of diagnosis) with at least one of the following confirmatory tests indicative of diagnosis:

      * 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
   2. Rebiopsy of a node at relapse is recommended but not required.
   3. Bone marrow biopsy required for pretreatment evaluation. Bilateral biopsies are not required.
2. Identification of HLA-Matched sibling donor - The sibling donor must meet eligibility criteria outlined in section 5.0
3. Prior Therapy

   1. Patients who have failed initial therapy are eligible (without any of the poor prognostic characteristics listed in the protocol). Failure to initial treatment is defined as one of the following:

      * Failure to achieve clinical complete remission after treatment with an anthracycline-containing regimen
      * Disease recurrence after initial treatment (with an anthracycline-containing regimen)
   2. Patients in first remission must have one of the following poor prognostic characteristics:

      * International Prognostic Index (IPI) score \> 1. IPI risk factors include the following: age \> 60 (not eligible for this protocol); performance status \> 1; LDH \> normal; presence of \> 1 extranodal sites; and stage III/IV disease
      * Blastic variant of mantle cell lymphoma (regardless of IPI score)
      * Complex karyotypes (i.e., cytogenetic abnormalities different from or in addition to t(11;14) (regardless of IPI score)
      * Proliferative index \> 10% (regardless of IPI score)
      * Presence of p53 mutations
   3. Patients who have received more than two chemotherapy regimens are ineligible. Patients who have undergone a prior bone marrow transplant are not eligible.
4. Age \< 60 years
5. No active CNS lymphoma
6. DLCO ≥ 40% and no symptomatic pulmonary disease
7. No HIV infection
8. Non-pregnant and non-nursing. Treatment under this protocol would expose an unborn child to significant risks. Women and men of reproductive potential should agree to use an effective means of birth control.
9. Initial required laboratory values

   * bilirubin \< 2 mg/dl
   * AST ≤ 3 x upper limit of normal (ULN)
   * ALT ≤ 3 x ULN
   * serum creatinine \< 2 mg/dl
   * u-HCG or serum HCG negative (if patient of childbearing potential)

Primary outcomes:
measure: disease free survival
timeFrame: up to 5 years post-transplant
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Veterans Affairs Medical Center - Birmingham
state: Alabama
city: La Jolla
country: United States
facility: University of California San Diego Cancer Center
state: California
city: San Francisco
country: United States
facility: Veterans Affairs Medical Center - San Francisco
state: California
city: San Francisco
country: United States
facility: UCSF Cancer Center and Cancer Research Institute
state: California
city: Wilmington
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Washington
country: United States
facility: Lombardi Cancer Center
state: District of Columbia
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Chicago (Westside Hospital)
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center
state: Iowa
city: Togus
country: United States
facility: Veterans Affairs Medical Center - Togus
state: Maine
city: Baltimore
country: United States
facility: Marlene and Stewart Greenebaum Cancer Center, University of Maryland
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center - University Campus
state: Massachusetts
city: Minneapolis
country: United States
facility: Veterans Affairs Medical Center - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Columbia
country: United States
facility: Veterans Affairs Medical Center - Columbia (Truman Memorial)
state: Missouri
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center - Columbia
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: CCOP - Southern Nevada Cancer Research Foundation
state: Nevada
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center
state: New Hampshire
city: Buffalo
country: United States
facility: Veterans Affairs Medical Center - Buffalo
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Manhasset
country: United States
facility: CCOP - North Shore University Hospital
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital - Cornell Campus
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center, NY
state: New York
city: Syracuse
country: United States
facility: State University of New York - Upstate Medical University
state: New York
city: Syracuse
country: United States
facility: Veterans Affairs Medical Center - Syracuse
state: New York
city: Syracuse
country: United States
facility: CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center, UNC
state: North Carolina
city: Durham
country: United States
facility: Veterans Affairs Medical Center - Durham
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: CCOP - Southeast Cancer Control Consortium
state: North Carolina
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital - Ohio State University
state: Ohio
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Memphis
country: United States
facility: University of Tennessee Cancer Institute
state: Tennessee
city: Memphis
country: United States
facility: Veterans Affairs Medical Center - Memphis
state: Tennessee
city: Bennington
country: United States
facility: Green Mountain Oncology Group
state: Vermont
city: Burlington
country: United States
facility: Vermont Cancer Center
state: Vermont
city: White River Junction
country: United States
facility: Veterans Affairs Medical Center - White River Junction
state: Vermont
city: Richmond
country: United States
facility: Veterans Affairs Medical Center - Richmond
state: Virginia
city: Richmond
country: United States
facility: MBCCOP - Massey Cancer Center
state: Virginia
Study officials:
affiliation: University of Chicago
name: Koen Van Besien, MD
role: STUDY_CHAIR
References: