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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00477412
Recruitment Status : Active, not recruiting
First Posted : May 23, 2007
Last Update Posted : March 26, 2018
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
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 or disease Intervention/treatment Phase
Mantle Cell Lymphoma Lymphoma Drug: Bortezomib Drug: Rituximab Drug: Cyclophosphamide Drug: Vincristine Drug: Methotrexate Drug: Cytarabine Drug: Doxorubicin Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Intervention Model: Single Group Assignment
Masking: None (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
Actual Study Start Date : April 2007
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : April 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
U.S. FDA Resources

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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, up to 1 year ]
    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 :
  1. Median Time to Failure (TTF) [ Time Frame: Up to 10 years ]
    Failure defined as time from initiation of treatment to recurrence/progression of disease or death from either disease or toxicity. Participants will be followed for an additional 2 years after completion of the treatment.

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Ages Eligible for Study:   18 Years to 79 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00477412

United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Millennium Pharmaceuticals, Inc.
Principal Investigator: Michael Wang, MD, MS M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT00477412     History of Changes
Other Study ID Numbers: 2006-0697
NCI-2010-00884 ( Registry Identifier: NCI CTRP )
First Posted: May 23, 2007    Key Record Dates
Last Update Posted: March 26, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Mantle Cell Lymphoma
Cytosine arabinosine hydrochloride

Additional relevant MeSH terms:
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Liposomal doxorubicin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors