Rituximab-HCVAD in Patients With B-Cell Non-Hodgkin's Lymphoma - Full Text View

Sponsors and Collaborators:	M.D. Anderson Cancer Center Genentech
Information provided by:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00290498

Purpose

Objectives:

To evaluate the Overall response rate (ORR), Complete Response (CR + Cru), Disease-free survival (DFS), and progression-free survival (PFS) rate following therapy with Rituxan-HCVAD alternating with Rituximab with high-dose methotrexate/ara-C and standard R-CHOP in patients with newly diagnosed B-cell aggressive non-Hodgkin's lymphomas younger than 60 years old and with adjusted IPI 2 or higher adverse prognostic features. Progression-free survival will be done for 3-years.
Secondary objectives include: overall survival, toxicity profile.

Condition	Intervention	Phase
Lymphoma	Drug: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Dexamethasone Drug: Methotrexate Drug: Cytarabine Drug: Prednisone	Phase II

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Doxorubicin Doxorubicin hydrochloride Cyclophosphamide Cytarabine Cytarabine hydrochloride Dexamethasone Dexamethasone acetate Dexamethasone Sodium Phosphate Doxiproct plus Leucovorin Calcium Citrovorum factor Folinic acid calcium salt pentahydrate Leucovorin Methotrexate Prednisone Vincristine sulfate Vincristine Rituximab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety/Efficacy Study
Official Title:	Rituximab-HCVAD Alternating Rituximab-Methotrexate-Cytarabine Versus Standard Rituximab-CHOP Every 21 Days for Patients With Newly Diagnosed High Risk Aggressive B-Cell Non-Hodgkin's Lymphomas in Patients 60 Years Old or Younger

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

To find out which of two different chemotherapy drug combinations, R-CHOP and R-HCVAD, is more effective in treating B-cell lymphoma. [ Time Frame: 3 Years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To study the safety of these drug combinations. [ Time Frame: 3 Years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	60
Study Start Date:	August 2005
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental Rituximab-HCVAD alternating with Rituximab-Methotrexate-Cytarabine	Drug: Rituximab Arm A: Rituximab 375 mg/m² on day 1, Cycle 1 and alternating cycles. Arm B: Rituximab 375 mg/m² on day 1, Cycle 2 and alternating cycles. Drug: Cyclophosphamide Arm A: Cyclophosphamide 300 mg/m^2 IVPB over 3h Q 12h x 6 doses on Days 2-4, Cycle 1 and alternating cycles. Arm B: Cyclophosphamide 300 mg/m^2 IVPB over 3h Q 12h x 6 doses on Days 2-4 each cycle. Drug: Doxorubicin Arm A: Doxorubicin 50 mg/m^2/day IV over 15 minutes (12 hours after last dose of cyclophosphamide) on Day 5, Cycle 1 and alternating cycles. Drug: Vincristine Arm A: Vincristine 1.4 mg/m^2 (maximum 2 mg) IVPB on Days 5 (1-24 hours after last cyclophosphamide) and on day 12, Cycle 1 and alternating cycles. Arm B: Vincristine 1.4 mg/m^2 (maximum 2 mg) IVPB on Days 5 (1-24 hours after last cyclophosphamide) and on day 12 of each cycle. Drug: Dexamethasone Arm A: Dexamethasone 40 mg IV or P.O. daily x 4 on Days 2-5 and on days 12-15 of cycle 1 and alternating cycles. Drug: Methotrexate Arm A: Methotrexate 800 mg/m^2 IV over 22 hours on day 2, cycle 2 and alternating cycles. Drug: Cytarabine Arm B: Cytarabine 3 g/m^2 IV over 2 hours every 12 hours X 4 doses on days 3 & 4, cycle 2 and alternating cycles.
B: Active Comparator Rituximab-CHOP	Drug: Rituximab Arm A: Rituximab 375 mg/m² on day 1, Cycle 1 and alternating cycles. Arm B: Rituximab 375 mg/m² on day 1, Cycle 2 and alternating cycles. Drug: Cyclophosphamide Arm A: Cyclophosphamide 300 mg/m^2 IVPB over 3h Q 12h x 6 doses on Days 2-4, Cycle 1 and alternating cycles. Arm B: Cyclophosphamide 300 mg/m^2 IVPB over 3h Q 12h x 6 doses on Days 2-4 each cycle. Drug: Vincristine Arm A: Vincristine 1.4 mg/m^2 (maximum 2 mg) IVPB on Days 5 (1-24 hours after last cyclophosphamide) and on day 12, Cycle 1 and alternating cycles. Arm B: Vincristine 1.4 mg/m^2 (maximum 2 mg) IVPB on Days 5 (1-24 hours after last cyclophosphamide) and on day 12 of each cycle. Drug: Prednisone Arm B: Prednisone by mouth (as a pill, capsule, or tablet) once a day on Days 1-5, each cycle.

Arms

Assigned Interventions

A: Experimental

Rituximab-HCVAD alternating with Rituximab-Methotrexate-Cytarabine

Drug: Rituximab

Arm A: Rituximab 375 mg/m² on day 1, Cycle 1 and alternating cycles. Arm B: Rituximab 375 mg/m² on day 1, Cycle 2 and alternating cycles.

Drug: Cyclophosphamide

Arm A: Cyclophosphamide 300 mg/m^2 IVPB over 3h Q 12h x 6 doses on Days 2-4, Cycle 1 and alternating cycles.

Arm B: Cyclophosphamide 300 mg/m^2 IVPB over 3h Q 12h x 6 doses on Days 2-4 each cycle.

Drug: Doxorubicin

Arm A: Doxorubicin 50 mg/m^2/day IV over 15 minutes (12 hours after last dose of cyclophosphamide) on Day 5, Cycle 1 and alternating cycles.

Drug: Vincristine

Arm A: Vincristine 1.4 mg/m^2 (maximum 2 mg) IVPB on Days 5 (1-24 hours after last cyclophosphamide) and on day 12, Cycle 1 and alternating cycles.

Arm B: Vincristine 1.4 mg/m^2 (maximum 2 mg) IVPB on Days 5 (1-24 hours after last cyclophosphamide) and on day 12 of each cycle.

Drug: Dexamethasone

Arm A: Dexamethasone 40 mg IV or P.O. daily x 4 on Days 2-5 and on days 12-15 of cycle 1 and alternating cycles.

Drug: Methotrexate

Arm A: Methotrexate 800 mg/m^2 IV over 22 hours on day 2, cycle 2 and alternating cycles.

Drug: Cytarabine

Arm B: Cytarabine 3 g/m^2 IV over 2 hours every 12 hours X 4 doses on days 3 & 4, cycle 2 and alternating cycles.

B: Active Comparator

Rituximab-CHOP

Drug: Rituximab

Arm A: Rituximab 375 mg/m² on day 1, Cycle 1 and alternating cycles. Arm B: Rituximab 375 mg/m² on day 1, Cycle 2 and alternating cycles.

Drug: Cyclophosphamide

Arm A: Cyclophosphamide 300 mg/m^2 IVPB over 3h Q 12h x 6 doses on Days 2-4, Cycle 1 and alternating cycles.

Arm B: Cyclophosphamide 300 mg/m^2 IVPB over 3h Q 12h x 6 doses on Days 2-4 each cycle.

Drug: Vincristine

Arm A: Vincristine 1.4 mg/m^2 (maximum 2 mg) IVPB on Days 5 (1-24 hours after last cyclophosphamide) and on day 12, Cycle 1 and alternating cycles.

Arm B: Vincristine 1.4 mg/m^2 (maximum 2 mg) IVPB on Days 5 (1-24 hours after last cyclophosphamide) and on day 12 of each cycle.

Drug: Prednisone

Arm B: Prednisone by mouth (as a pill, capsule, or tablet) once a day on Days 1-5, each cycle.

Show Detailed Description

Eligibility

Ages Eligible for Study:	16 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion:

Confirmed diagnosis of previously untreated large B-cell Non Hodgkin's. Other aggressive lymphomas such as Primary Mediastinal large B-cell Lymphomas will be also allowed to be included.
Patients with performance status of 0-2 (Zubrod Scale).
Serum bilirubin <1.5 mg/dl and serum creatinine < 2.0 mg/dl unless due to lymphoma; ANC >1000/mm^3 and platelets >100,000/mm^3 unless due to lymphoma.
Cardiac ejection fraction 50% or greater.
Ages 16 - 60 years (due to the fact that CHOP-R is not studied enough in younger patients and is not considered standard of care).
Patients must be willing to receive transfusions of blood products.
Age adjusted International Prognostic Index Score of 2 or more
Previous steroids are allowed (if used to relieve some symptoms such as SVC, etc).

Exclusion:

Pregnancy (excluded due to the teratogenicity of the involved chemotherapy agents
Positive HIV serology because of poor tolerance to this intense chemotherapy regimen
Burkitt's lymphomas, Burkitt's like, and Mantle cell lymphoma, transformed follicular center cell lymphoma, follicular grade III.
Any clinical or cytological diagnosis of CNS involvement
Any co-morbid medical, such as Child's Class C liver cirrhosis, end-stage renal disease, and symptomatic congestive heart failure, or psychiatric illnesses that preclude treatment with intense dose chemotherapy as determined by the primary investigator.
Concurrent or previous malignancy whose prognosis is poor (< 90% probability of survival at 5 years)
Active Hepatitis B or C. Chronic carriers for Hepatitis B will be excluded.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00290498

Contacts

Contact: Luis E. Fayad, MD

713-792-2860

Locations

United States, Texas
U.T.M.D Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Luis E. Fayad, MD

Sponsors and Collaborators

M.D. Anderson Cancer Center

Genentech

Investigators

Principal Investigator:

Luis E. Fayad, MD

U.T.M.D. Anderson Cancer Center

More Information

UT MD Anderson Cancer Center This link exits the ClinicalTrials.gov site

Responsible Party:	U.T.M.D. Anderson Cancer Center ( Luis E. Fayad, MD/Assoc. Professor )
Study ID Numbers:	2005-0054
Study First Received:	February 10, 2006
Last Updated:	November 10, 2008
ClinicalTrials.gov Identifier:	NCT00290498
Health Authority:	United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:

Non-Hodgkin's Lymphoma
B-Cell Non-Hodgkin's Lymphoma
Lymphoma
Cyclophosphamide
Cytarabine
Doxorubicin
Hyper-CVAD
Methotrexate
Prednisone
Rituximab
Vincristine
R-CHOP

R-HCVAD
Dexamethasone
Decadron
Leucovorin
Ara-C
Cytosar
Cytoxan
DepoCyt
Cytosine arabinosine hydrochloride
AD
Hydroxydaunomycin hydrochloride
Neosar

Study placed in the following topic categories:

Dexamethasone
Prednisone
Immunoproliferative Disorders
Rituximab
Lymphoma, small cleaved-cell, diffuse
Vincristine
Leucovorin
Cyclophosphamide
Doxorubicin
Folic Acid
Lymphoma, B-Cell

Lymphatic Diseases
B-cell lymphomas
Methotrexate
Hyperkinesis
Lymphoma, Non-Hodgkin
Aggression
Lymphoproliferative Disorders
Lymphoma
Cytarabine
Dexamethasone acetate

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Reproductive Control Agents
Antibiotics, Antineoplastic
Hormones
Therapeutic Uses
Abortifacient Agents

Dermatologic Agents
Alkylating Agents
Nucleic Acid Synthesis Inhibitors
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Mitosis Modulators
Gastrointestinal Agents
Enzyme Inhibitors
Antimitotic Agents
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Immunosuppressive Agents
Antiviral Agents
Glucocorticoids

ClinicalTrials.gov processed this record on January 16, 2009