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Bortezomib (Velcade) Plus Rituximab-HyperCVAD in Patients With Mantle Cell Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00477412
First received: May 21, 2007
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

The goal of this clinical research study is to learn if bortezomib (in combination with rituximab plus 2 different intensive chemotherapy regimens) can help to control the disease in patients with mantle cell lymphoma. The safety of these drug combinations will also be studied.


Condition Intervention Phase
Mantle Cell Lymphoma
Lymphoma
Drug: Bortezomib
Drug: Rituximab
Drug: Cyclophosphamide
Drug: Vincristine
Drug: Methotrexate
Drug: Cytarabine
Drug: Doxorubicin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Bortezomib (Velcade) Plus Rituximab-HyperCVAD Alternating With Bortezomib Plus Rituximab-High Dose Methotrexate/Cytarabine in Patients With Untreated Aggressive Mantle Cell Lymphoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Bortezomib Added to Combination of Rituximab, Methotrexate, and Cytarabine Alternating with Bortezomib, Rituximab-HyperCVAD [ Time Frame: Continual reassessment for toxicity with each 21 day cycle ] [ Designated as safety issue: Yes ]
    MTD defined as highest dose of bortezomib in which 2 or fewer patients in 6 treated experiences a dose limiting toxicity (DLT) among dose levels tested. DLT defined as a grade 3-4 non-hematologic toxicity that can not be ameliorated, prevented, or controlled with standard prophylactic therapy such as, but not limited to, nausea, vomiting, fatigue, diarrhea, constipation, low electrolyte levels, or tumor pain.


Secondary Outcome Measures:
  • Time to Failure (TTF) [ Time Frame: After 2, 21 day cycles ] [ Designated as safety issue: Yes ]
    Failure defined as recurrence/progression of disease or death from either disease or toxicity. Bayesian toxicity monitoring schema used to monitor severe toxicity profile in combined therapy. "Severe toxicity" per patient defined as at least two episodes of neutropenic fever during treatment courses, or grade 3-4 neuropathy during course of the patient's treatment. Time-to-event outcomes, including TTF, response duration, and overall survival, estimated using Kaplan-Meier method. Log-rank test performed to test difference in time-to-event distributions between patient groups. Cox proportional hazards model utilized to evaluate effects of covariates on time-to-event analysis.


Estimated Enrollment: 110
Study Start Date: April 2007
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bortezomib + Cyclophosphamide/Rituximab
1st Combination, Cycles 1,3,5 & 7 (if needed): Bortezomib + Rituximab + Cyclophosphamide + Doxorubicin + Vincristine; 2nd Combination, Cycles 2,4,6 & 8 (if needed): Rituximab + Methotrexate + Cytarabine.
Drug: Bortezomib
1st Combination = 1.3 mg/m^2 IV Push Over 3-5 Seconds Days 2 & 5; 2nd Combination = 0.7 mg/m^2 IV Push Days 1 & 6.
Other Names:
  • Velcade
  • PS-341
  • LDP-341
  • MLN341
Drug: Rituximab
375 mg/m^2 IV Over 6-8 Hours On Day 1 each cycle.
Other Name: Rituxan
Drug: Cyclophosphamide
1st Combination = 300 mg/m^2 IV Over 3 Hours Twice Daily Days 2,3,& 4.
Other Name: Cytoxan
Drug: Vincristine
1st Combination = 1.4 mg/m^2 (maximum 2 mg) IV Push Days 5 & 12.
Drug: Methotrexate
2nd Combination = 200 mg/m^2 IV over 2 hours on Day 1, then 800 mg/m^2 IV over 22 hours on Day 2.
Drug: Cytarabine
2nd Combination = 3g/m2 grams/m^2 IV over 2 Hours Twice a Day,On Days 3 & 4.
Other Names:
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine arabinosine hydrochloride
Drug: Doxorubicin
Arm 1: 50 mg/m^2 IV Push Over 15-30 min on Day 5
Other Names:
  • Adriamycin
  • Rubex

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Confirmed diagnosis of previously untreated nodular or diffuse mantle cell lymphoma and their blastoid cytologic variant.
  2. ECOG Performance status of 0, 1, or 2.
  3. Serum bilirubin <1.5mg/dl and serum creatinine < 2.0 mg/dl within 14 dyas before enrollment (unless higher levels are due to lymphoma)
  4. Platelet count>100,000/mm^3 and absolute neutrophil count (ANC)>1,000/mm^3 within 14 days before enrollment (unless due to lymphoma).
  5. Cardiac ejection fraction >/= 50% by ECHO or MUGA.
  6. Age 18 years to 79 years.
  7. Patients must be willing to receive transfusions of blood products.
  8. Voluntary written IRB-approved informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
  9. Female subject is either post-menopausal for at least 1 year before the Screening visit or surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of birth control, at the same time (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) from the time of signing the informed consent through 30 days after the last dose of study treatment, or agree to completely abstain from heterosexual intercourse.
  10. Male subject, even if surgically sterilized (ie, status post vasectomy) agrees to practice effective barrier contraception during the entire study treatment period and through 30 days after the last dose of study treatment, or agree to completely abstain from heterosexual intercourse.

Exclusion Criteria:

  1. HIV infection.
  2. CNS involvement.
  3. Co-morbid medical or psychiatric illnesses that preclude treatment with intense dose chemotherapy.
  4. Concurrent or previous malignancy with < 90% probability of survival at 5 years.
  5. Patient has >/= Grade 2 peripheral neuropathy within 14 days before enrollment.
  6. Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
  7. Patient has hypersensitivity to bortezomib, boron or mannitol.
  8. Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
  9. Participating in clinical trials with other investigational agents not included in this trial within 14 days of the start of this trial and throughout the duration of this trial.
  10. Radiation therapy within 3 weeks before randomization. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00477412

Locations
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Jorge Romaguera, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00477412     History of Changes
Other Study ID Numbers: 2006-0697, NCI-2010-00884
Study First Received: May 21, 2007
Last Updated: July 21, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Mantle Cell Lymphoma
Lymphoma
Bortezomib
LDP-341
MLN341
Velcade
Cyclophosphamide
Neosar
Cytoxan
Doxorubicin
Adriamycin
Rubex
Rituximab
Vincristine
Methotrexate
Cytarabine
Cytosar
DepoCyt
Cytosine arabinosine hydrochloride
Mesna
Dexamethasone

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Bortezomib
Cyclophosphamide
Cytarabine
Doxorubicin
Liposomal doxorubicin
Methotrexate
Rituximab
Vincristine
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Antiviral Agents

ClinicalTrials.gov processed this record on November 20, 2014