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

NCT ID: NCT00020943

Last Updated: 2016-07-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

79 participants

Study Classification

INTERVENTIONAL

Study Start Date

2001-06-30

Study Completion Date

2009-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Chemo/immuno/autolog transplant

Intensive chemotherapy followed by autologous stem cell transplant and immunotherapy for mantle cell lymphoma

Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

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

rituximab

Intervention Type BIOLOGICAL

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

carmustine

Intervention Type DRUG

15 mg/kg IV infusion over 2 hours Day 6, Tx 4

cyclophosphamide

Intervention Type DRUG

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

cytarabine

Intervention Type DRUG

2000 mg/sq m IV infusion BID over 2 hours x 8 doses Days 1-4, Tx 3

doxorubicin hydrochloride

Intervention Type DRUG

50 mg/sq m IVP Day 3, Tx 1\& 2

etoposide

Intervention Type DRUG

40 mg/kg total dose continuous IV infusion over 96 hours Days 1-4, Tx 3

leucovorin calcium

Intervention Type DRUG

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

methotrexate

Intervention Type DRUG

300 mg/sq m IV infusion over 4 hrs Day 2 Tx 1 \& 2

prednisone

Intervention Type DRUG

100 mg/sq m PO Days 3-7, Tx 1 \& 2

vincristine sulfate

Intervention Type DRUG

1.4 mg/sq m IVP Day 3, Tx 1 \& 2

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

Stem cells collected during Tx 3 will be transfused follwing chemotx in Tx 4

Interventions

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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

Intervention Type 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

Intervention Type BIOLOGICAL

carmustine

15 mg/kg IV infusion over 2 hours Day 6, Tx 4

Intervention Type 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

Intervention Type DRUG

cytarabine

2000 mg/sq m IV infusion BID over 2 hours x 8 doses Days 1-4, Tx 3

Intervention Type DRUG

doxorubicin hydrochloride

50 mg/sq m IVP Day 3, Tx 1\& 2

Intervention Type DRUG

etoposide

40 mg/kg total dose continuous IV infusion over 96 hours Days 1-4, Tx 3

Intervention Type 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

Intervention Type DRUG

methotrexate

300 mg/sq m IV infusion over 4 hrs Day 2 Tx 1 \& 2

Intervention Type DRUG

prednisone

100 mg/sq m PO Days 3-7, Tx 1 \& 2

Intervention Type DRUG

vincristine sulfate

1.4 mg/sq m IVP Day 3, Tx 1 \& 2

Intervention Type DRUG

peripheral blood stem cell transplantation

Stem cells collected during Tx 3 will be transfused follwing chemotx in Tx 4

Intervention Type PROCEDURE

Other Intervention Names

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G-CSF ara-C

Eligibility Criteria

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Inclusion Criteria

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

69 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lloyd Damon, MD

Role: STUDY_CHAIR

University of California, San Francisco

Locations

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Northeast Alabama Regional Medical Center

Anniston, Alabama, United States

Site Status

Veterans Affairs Medical Center - Birmingham

Birmingham, Alabama, United States

Site Status

Rebecca and John Moores UCSD Cancer Center

La Jolla, California, United States

Site Status

Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

Naval Medical Center - San Diego

San Diego, California, United States

Site Status

Veterans Affairs Medical Center - San Diego

San Diego, California, United States

Site Status

UCSF Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Veterans Affairs Medical Center - San Francisco

San Francisco, California, United States

Site Status

Hematology/Oncology Faculty Practice

San Francisco, California, United States

Site Status

CCOP - Christiana Care Health Services

Newark, Delaware, United States

Site Status

Lombardi Cancer Center at Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Site Status

Walter Reed Army Medical Center

Washington D.C., District of Columbia, United States

Site Status

Veterans Affairs Medical Center - Washington, DC

Washington D.C., District of Columbia, United States

Site Status

Broward General Medical Center

Fort Lauderdale, Florida, United States

Site Status

Memorial Regional Cancer Center at Memorial Regional Hospital

Hollywood, Florida, United States

Site Status

CCOP - Mount Sinai Medical Center

Miami Beach, Florida, United States

Site Status

Palm Beach Cancer Institute

West Palm Beach, Florida, United States

Site Status

Veterans Affairs Medical Center - Chicago (Westside Hospital)

Chicago, Illinois, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

Louis A. Weiss Memorial Hospital

Chicago, Illinois, United States

Site Status

CCOP - Illinois Oncology Research Association

Peoria, Illinois, United States

Site Status

West Suburban Center for Cancer Care

River Forest, Illinois, United States

Site Status

Fort Wayne Medical Oncology and Hematology, Incorporated

Fort Wayne, Indiana, United States

Site Status

CCOP - Northern Indiana CR Consortium

South Bend, Indiana, United States

Site Status

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, United States

Site Status

Baptist Hospital East - Louisville

Louisville, Kentucky, United States

Site Status

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

UMASS Memorial Cancer Center - University Campus

Worcester, Massachusetts, United States

Site Status

Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph

Saint Joseph, Michigan, United States

Site Status

Veterans Affairs Medical Center - Minneapolis

Minneapolis, Minnesota, United States

Site Status

University of Minnesota Cancer Center

Minneapolis, Minnesota, United States

Site Status

Veterans Affairs Medical Center - Columbia (Truman Memorial)

Columbia, Missouri, United States

Site Status

Ellis Fischel Cancer Center at University of Missouri - Columbia

Columbia, Missouri, United States

Site Status

CCOP - Kansas City

Kansas City, Missouri, United States

Site Status

Siteman Cancer Center at Barnes-Jewish Hospital

St Louis, Missouri, United States

Site Status

Missouri Baptist Cancer Center

St Louis, Missouri, United States

Site Status

UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

CCOP - Southern Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

Site Status

Veterans Affairs Medical Center - Las Vegas

Las Vegas, Nevada, United States

Site Status

New Hampshire Oncology-Hematology, PA - Hooksett

Hooksett, New Hampshire, United States

Site Status

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Cooper University Hospital

Camden, New Jersey, United States

Site Status

Veterans Affairs Medical Center - Buffalo

Buffalo, New York, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.

East Syracuse, New York, United States

Site Status

Elmhurst Hospital Center

Elmhurst, New York, United States

Site Status

Queens Cancer Center of Queens Hospital

Jamaica, New York, United States

Site Status

CCOP - North Shore University Hospital

Manhasset, New York, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

New York Weill Cornell Cancer Center at Cornell University

New York, New York, United States

Site Status

Mount Sinai Medical Center

New York, New York, United States

Site Status

University Hospital at State University of New York - Upstate Medical University

Syracuse, New York, United States

Site Status

Veterans Affairs Medical Center - Syracuse

Syracuse, New York, United States

Site Status

Veterans Affairs Medical Center - Asheville

Asheville, North Carolina, United States

Site Status

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

NorthEast Oncology Associates - Concord

Concord, North Carolina, United States

Site Status

Veterans Affairs Medical Center - Durham

Durham, North Carolina, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

Cape Fear Valley Health System

Fayetteville, North Carolina, United States

Site Status

CCOP - Southeast Cancer Control Consortium

Goldsboro, North Carolina, United States

Site Status

Lenoir Memorial Hospital Cancer Center

Kinston, North Carolina, United States

Site Status

FirstHealth Moore Regional Hospital

Pinehurst, North Carolina, United States

Site Status

Zimmer Cancer Center at New Hanover Regional Medical Center

Wilmington, North Carolina, United States

Site Status

Comprehensive Cancer Center at Wake Forest University

Winston-Salem, North Carolina, United States

Site Status

Arthur G. James Cancer Hospital at Ohio State University

Columbus, Ohio, United States

Site Status

Oklahoma University Medical Center

Oklahoma City, Oklahoma, United States

Site Status

Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Lifespan: The Miriam Hospital

Providence, Rhode Island, United States

Site Status

University of Tennessee Cancer Institute

Memphis, Tennessee, United States

Site Status

Veterans Affairs Medical Center - Memphis

Memphis, Tennessee, United States

Site Status

Veterans Affairs Medical Center - Dallas

Dallas, Texas, United States

Site Status

Green Mountain Oncology Group

Bennington, Vermont, United States

Site Status

Vermont Cancer Center at University of Vermont

Burlington, Vermont, United States

Site Status

Martha Jefferson Hospital

Charlottesville, Virginia, United States

Site Status

Virginia Oncology Associates - Norfolk

Norfolk, Virginia, United States

Site Status

MBCCOP - Massey Cancer Center

Richmond, Virginia, United States

Site Status

Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke

Roanoke, Virginia, United States

Site Status

St. Mary's Medical Center

Huntington, West Virginia, United States

Site Status

Puerto Rico Cancer Center at University of Puerto Rico - Medical Sciences Campus

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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Damon LE, Johnson JL, Niedzwiecki D, Cheson BD, Hurd DD, Bartlett NL, Lacasce AS, Blum KA, Byrd JC, Kelly M, Stock W, Linker CA, Canellos GP. Immunochemotherapy and autologous stem-cell transplantation for untreated patients with mantle-cell lymphoma: CALGB 59909. J Clin Oncol. 2009 Dec 20;27(36):6101-8. doi: 10.1200/JCO.2009.22.2554. Epub 2009 Nov 16.

Reference Type RESULT
PMID: 19917845 (View on PubMed)

Hsi ED, Jung SH, Lai R, Johnson JL, Cook JR, Jones D, Devos S, Cheson BD, Damon LE, Said J. Ki67 and PIM1 expression predict outcome in mantle cell lymphoma treated with high dose therapy, stem cell transplantation and rituximab: a Cancer and Leukemia Group B 59909 correlative science study. Leuk Lymphoma. 2008 Nov;49(11):2081-90. doi: 10.1080/10428190802419640.

Reference Type RESULT
PMID: 19021050 (View on PubMed)

Damon LE, Johnson J, Niedzwiecki D, et al.: Immuno-chemotherapy (IC) and autologous stem cell transplant (ASCT) for untreated patients (pts) with mantle cell lymphoma (MCL): CALGB 59909. [Abstract] Blood 108 (11): A-2737, 2006.

Reference Type RESULT

Liu H, Johnson JL, Koval G, Malnassy G, Sher D, Damon LE, Hsi ED, Bucci DM, Linker CA, Cheson BD, Stock W. Detection of minimal residual disease following induction immunochemotherapy predicts progression free survival in mantle cell lymphoma: final results of CALGB 59909. Haematologica. 2012 Apr;97(4):579-85. doi: 10.3324/haematol.2011.050203. Epub 2011 Nov 18.

Reference Type DERIVED
PMID: 22102709 (View on PubMed)

Other Identifiers

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U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CALGB-59909

Identifier Type: -

Identifier Source: secondary_id

CDR0000068732

Identifier Type: REGISTRY

Identifier Source: secondary_id

CALGB-59909

Identifier Type: -

Identifier Source: org_study_id

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