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

Lymphoma Clinical Trial

Official title:

Allogeneic Stem Cell Transplantation for Mantle Cell Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006747
• Other study ID #: CALGB-59908
• Secondary ID: U10CA031946CLB-5
• Status: Completed
• Phase: Phase 2
• First received: December 6, 2000
• Last updated: July 15, 2016
• Start date: November 2000
• Est. completion date: February 2003

Study information

• Verified date: July 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4
• Est. completion date: February 2003
• Est. primary completion date: February 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 59 Years

Eligibility

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)

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease
• Lymphoma
• Lymphoma, Mantle-Cell

Intervention

Drug:
• carmustine
IV
• melphalan
IV
• etoposide
IV
• cytarabine
IV
• tacrolimus
IV
• methotrexate
IV
• sargramostim
IV

Procedure:
• transplant

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	disease free survival		up to 5 years post-transplant	No