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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00020943
• Other study ID #: CALGB-59909
• Secondary ID: U10CA031946CALGB
• Status: Completed
• Phase: Phase 2
• First received: July 11, 2001
• Last updated: July 15, 2016
• Start date: June 2001
• Est. completion date: September 2009

Study information

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

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: September 2009
• Est. primary completion date: December 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 69 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell

Intervention

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
• 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
• 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
• cytarabine
2000 mg/sq m IV infusion BID over 2 hours x 8 doses Days 1-4, Tx 3
• doxorubicin hydrochloride
50 mg/sq m IVP Day 3, Tx 1& 2
• etoposide
40 mg/kg total dose continuous IV infusion over 96 hours Days 1-4, Tx 3
• 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
• methotrexate
300 mg/sq m IV infusion over 4 hrs Day 2 Tx 1 & 2
• prednisone
100 mg/sq m PO Days 3-7, Tx 1 & 2
• 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

Locations

Country	Name	City	State
Puerto Rico	Puerto Rico Cancer Center at University of Puerto Rico - Medical Sciences Campus	San Juan
United States	Northeast Alabama Regional Medical Center	Anniston	Alabama
United States	Veterans Affairs Medical Center - Asheville	Asheville	North Carolina
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	Green Mountain Oncology Group	Bennington	Vermont
United States	Veterans Affairs Medical Center - Birmingham	Birmingham	Alabama
United States	Dana-Farber/Harvard Cancer Center at 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 at University of Vermont	Burlington	Vermont
United States	Cooper University Hospital	Camden	New Jersey
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Martha Jefferson Hospital	Charlottesville	Virginia
United States	Louis A. Weiss Memorial Hospital	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Veterans Affairs Medical Center - Chicago (Westside Hospital)	Chicago	Illinois
United States	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri
United States	Veterans Affairs Medical Center - Columbia (Truman Memorial)	Columbia	Missouri
United States	Arthur G. James Cancer Hospital at Ohio State University	Columbus	Ohio
United States	NorthEast Oncology Associates - Concord	Concord	North Carolina
United States	Veterans Affairs Medical Center - Dallas	Dallas	Texas
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Veterans Affairs Medical Center - Durham	Durham	North Carolina
United States	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	East Syracuse	New York
United States	Elmhurst Hospital Center	Elmhurst	New York
United States	Cape Fear Valley Health System	Fayetteville	North Carolina
United States	Broward General Medical Center	Fort Lauderdale	Florida
United States	Fort Wayne Medical Oncology and Hematology, Incorporated	Fort Wayne	Indiana
United States	CCOP - Southeast Cancer Control Consortium	Goldsboro	North Carolina
United States	Memorial Regional Cancer Center at Memorial Regional Hospital	Hollywood	Florida
United States	New Hampshire Oncology-Hematology, PA - Hooksett	Hooksett	New Hampshire
United States	St. Mary's Medical Center	Huntington	West Virginia
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	Queens Cancer Center of Queens Hospital	Jamaica	New York
United States	CCOP - Kansas City	Kansas City	Missouri
United States	Lenoir Memorial Hospital Cancer Center	Kinston	North Carolina
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Veterans Affairs Medical Center - Las Vegas	Las Vegas	Nevada
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center	Los Angeles	California
United States	Baptist Hospital East - Louisville	Louisville	Kentucky
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	New York	New York
United States	New York Weill Cornell Cancer Center at Cornell University	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Virginia Oncology Associates - Norfolk	Norfolk	Virginia
United States	Oklahoma University Medical Center	Oklahoma City	Oklahoma
United States	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	FirstHealth Moore Regional Hospital	Pinehurst	North Carolina
United States	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	Lifespan: The Miriam Hospital	Providence	Rhode Island
United States	MBCCOP - Massey Cancer Center	Richmond	Virginia
United States	West Suburban Center for Cancer Care	River Forest	Illinois
United States	Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke	Roanoke	Virginia
United States	Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph	Saint Joseph	Michigan
United States	Missouri Baptist Cancer Center	Saint Louis	Missouri
United States	Siteman Cancer Center at Barnes-Jewish Hospital	Saint Louis	Missouri
United States	Naval Medical Center - San Diego	San Diego	California
United States	Veterans Affairs Medical Center - San Diego	San Diego	California
United States	Hematology/Oncology Faculty Practice	San Francisco	California
United States	UCSF Comprehensive Cancer Center	San Francisco	California
United States	Veterans Affairs Medical Center - San Francisco	San Francisco	California
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	University Hospital at State University of New York - Upstate Medical University	Syracuse	New York
United States	Veterans Affairs Medical Center - Syracuse	Syracuse	New York
United States	Lombardi Cancer Center at Georgetown University Medical Center	Washington	District of Columbia
United States	Veterans Affairs Medical Center - Washington, DC	Washington	District of Columbia
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	Palm Beach Cancer Institute	West Palm Beach	Florida
United States	Zimmer Cancer Center at New Hanover Regional Medical Center	Wilmington	North Carolina
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina
United States	UMASS Memorial Cancer Center - University Campus	Worcester	Massachusetts

Sponsors (2)

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

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (4)

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.

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: CAL — View Citation

Hsi E, Jung S, Lai R, et al.: Ki67 and PIM1 expression in aggressively treated mantle cell lymphoma (MCL): A Cancer and Leukemia Group B (CALGB) 59909 correlative science study. [Abstract] J Clin Oncol 26 (Suppl 15): A-8560, 2008.

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 Gro — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival		2 years	No
Secondary	Response		2 years	No
Secondary	Survival	Disease free and overall survival	5 years	No