Chemotherapy and Rituximab With Peripheral Stem Cell Transplantation in Treating Patients With Mantle Cell Lymphoma

July 15, 2016 updated by: Alliance for Clinical Trials in Oncology

A Phase II Study Of Intensive Induction Chemotherapy Followed By Autologous Stem Cell Transplantation Plus Immunotherapy For Mantle Cell Lymphoma

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining chemotherapy and rituximab with peripheral stem cell transplantation in treating patients who have mantle cell lymphoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the two-year progression-free survival of patients with mantle cell lymphoma treated with intensive chemotherapy and rituximab with autologous peripheral blood stem cell (PBSC) transplantation.
  • Determine the complete and partial response rates of patients treated with this regimen.
  • Determine the disease-free and overall survival of patients treated with this regimen.
  • Determine the autologous immune reconstitution in patients treated with this regimen.
  • Determine the feasibility of this regimen in this patient population.
  • Determine whether treatment with rituximab during autologous PBSC transplantation reduces the amount of contaminating lymphoma in the autologous PBSC product.

OUTLINE: This is a multicenter study.

Patients receive induction therapy comprising rituximab IV over 4-6 hours on day 1; methotrexate IV over 4 hours on day 2; cyclophosphamide IV over 2 hours, doxorubicin IV, and vincristine IV on day 3; and oral prednisone on days 3-7. Patients also receive leucovorin calcium IV every 6 hours beginning on day 3 and continuing until blood levels of methotrexate are safe. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning on day 4 and continuing until blood counts recover.

Induction therapy repeats every 21-28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Rituximab may be omitted during course 1 if circulating mantle cells are excessive. Patients may receive a third course if more than 15% persistent bone marrow involvement is documented.

Patients with stable or responding disease begin consolidation therapy 29 days after the start of the final course of induction therapy. Patients receive cytarabine IV over 2 hours twice daily and etoposide IV over 96 hours on days 1-4. Patients also receive rituximab IV over 4-6 hours on days 5 or 6 and 12 or 13 and G-CSF SC beginning on day 14 and continuing until leukapheresis is complete. Patients undergo leukapheresis beginning between days 22-25 and continuing until adequate CD34 cells are collected.

Beginning 4 weeks after recovery from consolidation therapy, patients receive high-dose therapy comprising carmustine IV over 2 hours on day -6, etoposide IV over 4 hours on day -4, and cyclophosphamide IV over 2 hours on day -2. Patients undergo autologous peripheral blood stem cell (PBSC) transplantation on day 0. Patients receive G-CSF SC beginning on day 6 and continuing until blood counts recover.

After blood counts recover and more than 35 days after autologous PBSC transplantation, patients receive rituximab IV over 4-6 hours weekly for 2 weeks.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for up to 10 years.

PROJECTED ACCRUAL: At least 45 patients will be accrued for this study within 2 years.

Study Type

Interventional

Enrollment (Actual)

79

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • San Juan, Puerto Rico, 00936-5067
        • Puerto Rico Cancer Center at University of Puerto Rico - Medical Sciences Campus
  • United States
    • Alabama
      • Anniston, Alabama, United States, 36207
        • Northeast Alabama Regional Medical Center
      • Birmingham, Alabama, United States, 35233-1996
        • Veterans Affairs Medical Center - Birmingham
    • California
      • La Jolla, California, United States, 92093-0658
        • Rebecca and John Moores UCSD Cancer Center
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center
      • San Diego, California, United States, 92161
        • Veterans Affairs Medical Center - San Diego
      • San Diego, California, United States, 92134-3202
        • Naval Medical Center - San Diego
      • San Francisco, California, United States, 94115
        • UCSF Comprehensive Cancer Center
      • San Francisco, California, United States, 94121
        • Veterans Affairs Medical Center - San Francisco
      • San Francisco, California, United States, 94143-0324
        • Hematology/Oncology Faculty Practice
    • Delaware
      • Newark, Delaware, United States, 19713
        • CCOP - Christiana Care Health Services
    • District of Columbia
      • Washington, District of Columbia, United States, 20422
        • Veterans Affairs Medical Center - Washington, DC
      • Washington, District of Columbia, United States, 20007
        • Lombardi Cancer Center at Georgetown University Medical Center
      • Washington, District of Columbia, United States, 20307-5001
        • Walter Reed Army Medical Center
    • Florida
      • Fort Lauderdale, Florida, United States, 33316
        • Broward General Medical Center
      • Hollywood, Florida, United States, 33021
        • Memorial Regional Cancer Center at Memorial Regional Hospital
      • Miami Beach, Florida, United States, 33140
        • CCOP - Mount Sinai Medical Center
      • West Palm Beach, Florida, United States, 33401
        • Palm Beach Cancer Institute
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Veterans Affairs Medical Center - Chicago (Westside Hospital)
      • Chicago, Illinois, United States, 60637-1470
        • University of Chicago Cancer Research Center
      • Chicago, Illinois, United States, 60640
        • Louis A. Weiss Memorial Hospital
      • Peoria, Illinois, United States, 61615-7828
        • CCOP - Illinois Oncology Research Association
      • River Forest, Illinois, United States, 60305
        • West Suburban Center for Cancer Care
    • Indiana
      • Fort Wayne, Indiana, United States, 46885-5099
        • Fort Wayne Medical Oncology and Hematology, Incorporated
      • South Bend, Indiana, United States, 46601
        • CCOP - Northern Indiana CR Consortium
    • Iowa
      • Iowa City, Iowa, United States, 52242-1009
        • Holden Comprehensive Cancer Center at University of Iowa
    • Kentucky
      • Louisville, Kentucky, United States, 40207
        • Baptist Hospital East - Louisville
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Greenebaum Cancer Center at University of Maryland Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
      • Worcester, Massachusetts, United States, 01655
        • UMASS Memorial Cancer Center - University Campus
    • Michigan
      • Saint Joseph, Michigan, United States, 49085
        • Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph
    • Minnesota
      • Minneapolis, Minnesota, United States, 55417
        • Veterans Affairs Medical Center - Minneapolis
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Cancer Center
    • Missouri
      • Columbia, Missouri, United States, 65201
        • Veterans Affairs Medical Center - Columbia (Truman Memorial)
      • Columbia, Missouri, United States, 65203
        • Ellis Fischel Cancer Center at University of Missouri - Columbia
      • Kansas City, Missouri, United States, 64131
        • CCOP - Kansas City
      • Saint Louis, Missouri, United States, 63131
        • Missouri Baptist Cancer Center
      • Saint Louis, Missouri, United States, 63110
        • Siteman Cancer Center at Barnes-Jewish Hospital
    • Nebraska
      • Omaha, Nebraska, United States, 68198-7680
        • UNMC Eppley Cancer Center at the University of Nebraska Medical Center
    • Nevada
      • Las Vegas, Nevada, United States, 89106
        • CCOP - Southern Nevada Cancer Research Foundation
      • Las Vegas, Nevada, United States, 89106
        • Veterans Affairs Medical Center - Las Vegas
    • New Hampshire
      • Hooksett, New Hampshire, United States, 03106
        • New Hampshire Oncology-Hematology, PA - Hooksett
      • Lebanon, New Hampshire, United States, 03756-0002
        • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
    • New Jersey
      • Camden, New Jersey, United States, 08103
        • Cooper University Hospital
    • New York
      • Buffalo, New York, United States, 14263-0001
        • Roswell Park Cancer Institute
      • Buffalo, New York, United States, 14215
        • Veterans Affairs Medical Center - Buffalo
      • East Syracuse, New York, United States, 13057
        • CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
      • Elmhurst, New York, United States, 11373
        • Elmhurst Hospital Center
      • Jamaica, New York, United States, 11432
        • Queens Cancer Center of Queens Hospital
      • Manhasset, New York, United States, 11030
        • CCOP - North Shore University Hospital
      • Manhasset, New York, United States, 11030
        • North Shore University Hospital
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center
      • New York, New York, United States, 10021
        • New York Weill Cornell Cancer Center at Cornell University
      • New York, New York, United States, 10029
        • Mount Sinai Medical Center
      • Syracuse, New York, United States, 13210
        • Veterans Affairs Medical Center - Syracuse
      • Syracuse, New York, United States, 13210
        • University Hospital at State University of New York - Upstate Medical University
    • North Carolina
      • Asheville, North Carolina, United States, 28805
        • Veterans Affairs Medical Center - Asheville
      • Chapel Hill, North Carolina, United States, 27599-7295
        • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
      • Concord, North Carolina, United States, 28025
        • NorthEast Oncology Associates - Concord
      • Durham, North Carolina, United States, 27705
        • Veterans Affairs Medical Center - Durham
      • Durham, North Carolina, United States, 27710
        • Duke Comprehensive Cancer Center
      • Fayetteville, North Carolina, United States, 28302-2000
        • Cape Fear Valley Health System
      • Goldsboro, North Carolina, United States, 27534-9479
        • CCOP - Southeast Cancer Control Consortium
      • Kinston, North Carolina, United States, 28503-1678
        • Lenoir Memorial Hospital Cancer Center
      • Pinehurst, North Carolina, United States, 28374
        • Firsthealth Moore Regional Hospital
      • Wilmington, North Carolina, United States, 28402-9025
        • Zimmer Cancer Center at New Hanover Regional Medical Center
      • Winston-Salem, North Carolina, United States, 27157-1082
        • Comprehensive Cancer Center at Wake Forest University
    • Ohio
      • Columbus, Ohio, United States, 43210-1240
        • Arthur G. James Cancer Hospital at Ohio State University
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Oklahoma University Medical Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • Western Pennsylvania Hospital
    • Rhode Island
      • Providence, Rhode Island, United States, 02906
        • Lifespan: The Miriam Hospital
    • Tennessee
      • Memphis, Tennessee, United States, 38104
        • Veterans Affairs Medical Center - Memphis
      • Memphis, Tennessee, United States, 38104
        • University of Tennessee Cancer Institute
    • Texas
      • Dallas, Texas, United States, 75219
        • Veterans Affairs Medical Center - Dallas
    • Vermont
      • Bennington, Vermont, United States, 05201
        • Green Mountain Oncology Group
      • Burlington, Vermont, United States, 05401-3498
        • Vermont Cancer Center at University of Vermont
    • Virginia
      • Charlottesville, Virginia, United States, 22902
        • Martha Jefferson Hospital
      • Norfolk, Virginia, United States, 23502
        • Virginia Oncology Associates - Norfolk
      • Richmond, Virginia, United States, 23298-0037
        • MBCCOP - Massey Cancer Center
      • Roanoke, Virginia, United States, 24014
        • Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke
    • West Virginia
      • Huntington, West Virginia, United States, 25701
        • St. Mary's Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 69 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed mantle cell lymphoma

  • Presenting with at least one of the following:

    • Coexpression of CD20 (or CD19) and CD5 and a lack of CD23 expression by immunophenotyping
    • Positive for cyclin D1 by immunostaining
    • Presence of t(11,14) by cytogenetic analysis
    • Molecular evidence of bcl-1/IgH rearrangement

  • Stage I-IV disease

    • Stage III or IV if nodular histology mantle cell lymphoma present
    • Any stage for other mantle cell histologies
    • No mantle zone histology

  • No active CNS disease

    • No symptomatic meningeal lymphoma
    • No known CNS parenchymal lymphoma
    • Lumbar puncture showing mantle cell lymphoma allowed

  • Bidimensionally measurable disease greater than 1 cm

    • Nonmeasurable disease includes the following:

      • Bone lesions
      • Leptomeningeal disease
      • Ascites
      • Pleural/pericardial effusion
      • Inflammatory breast disease
      • Lymphangitis cutis/pulmonis
      • Abdominal masses not confirmed and followed by imaging techniques
      • Cystic lesions
      • Lesions in a previously irradiated area

PATIENT CHARACTERISTICS:

Age:

  • 18 to 69

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

  • Hepatitis B surface antigen and hepatitis C antibody positive patients must meet all of the following criteria:

    • Bilirubin no greater than 2 times upper limit of normal (ULN)
    • AST no greater than 3 times ULN
    • Liver biopsy shows no greater than grade 2 fibrosis and no cirrhosis

Renal:

  • Creatinine no greater than 2.0 mg/dL

Cardiovascular:

  • LVEF at least 45% by MUGA or echocardiogram

Other:

  • No known hypersensitivity to murine products
  • HIV negative
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No more than 1 prior dose of rituximab

Chemotherapy:

  • No more than 1 prior cycle of chemotherapy
  • At least 3 weeks since prior chemotherapy
  • No other concurrent chemotherapeutic agents

Endocrine therapy:

  • No chronic use of oral corticosteroids for ongoing medical condition
  • No concurrent hormonal therapy except for non-lymphoma-related conditions (e.g., insulin for diabetes)
  • Other concurrent corticosteroids for adrenal failure, diffuse alveolar hemorrhage, carmustine pneumonitis, or as an anti-emetic allowed

Radiotherapy:

  • No prior radiotherapy for mantle cell lymphoma
  • Concurrent palliative radiotherapy allowed
  • Concurrent cranial radiotherapy for asymptomatic meningeal lymphoma allowed

Surgery:

  • At least 2 weeks since prior major surgery

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Chemo/immuno/autolog transplant
Intensive chemotherapy followed by autologous stem cell transplant and immunotherapy for mantle cell lymphoma
Biological: filgrastim
5 ug/kg subQ daily day 4 until ANC >10,000 (or ANC> 5000 2X)Tx 1, 2, 4 10 ug/kg subQ daily day 14 until completion of PBSC collection Tx 3
Other Names:
  • G-CSF
Biological: rituximab
375 mg/sq m IV infusion at , or = 400 mg/hr day 1 Tx 1, 2, days 5 & 12 Tx 3, and weekly for 2 doses Tx 5
Drug: carmustine
15 mg/kg IV infusion over 2 hours Day 6, Tx 4
Drug: cyclophosphamide
2000 mg/sq m IV infusion over 2 hours Day 3, Tx 1 & 2 100 mg/kg IV infusion over 2 hours Day 2, Tx 4
Drug: cytarabine
2000 mg/sq m IV infusion BID over 2 hours x 8 doses Days 1-4, Tx 3
Other Names:
  • ara-C
Drug: doxorubicin hydrochloride
50 mg/sq m IVP Day 3, Tx 1& 2
Drug: etoposide
40 mg/kg total dose continuous IV infusion over 96 hours Days 1-4, Tx 3
Drug: leucovorin calcium
50 mg/sq m IV infusion q 6 hours x 3 doses after MTX, then 10 mg/sq m IV/PO q 6 hrs until MTX levels <0.05 uM, Tx 1 & 2
Drug: methotrexate
300 mg/sq m IV infusion over 4 hrs Day 2 Tx 1 & 2
Drug: prednisone
100 mg/sq m PO Days 3-7, Tx 1 & 2
Drug: vincristine sulfate
1.4 mg/sq m IVP Day 3, Tx 1 & 2
Procedure: peripheral blood stem cell transplantation
Stem cells collected during Tx 3 will be transfused follwing chemotx in Tx 4

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Progression Free Survival
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response
Time Frame: 2 years
2 years
Survival
Time Frame: 5 years
Disease free and overall survival
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alliance for Clinical Trials in Oncology

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Lloyd Damon, MD, University of California, San Francisco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2001

Primary Completion (Actual)

December 1, 2006

Study Completion (Actual)

September 1, 2009

Study Registration Dates

First Submitted

July 11, 2001

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

July 19, 2016

Last Update Submitted That Met QC Criteria

July 15, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CALGB-59909
  • U10CA031946 (U.S. NIH Grant/Contract)
  • CDR0000068732 (Registry Identifier: NCI Physician Data Query)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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