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Study of Bortezomib in Combination With Cyclophosphamide and Rituximab

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: NCT00958256
Recruitment Status : Completed
First Posted : August 13, 2009
Results First Posted : April 13, 2015
Last Update Posted : April 13, 2015
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 when given in combination with cyclophosphamide and rituximab can help to control mantle cell lymphoma. The safety of this drug combination will also continue to be studied.

Condition or disease Intervention/treatment Phase
Mantle Cell Lymphoma Lymphoma Drug: Bortezomib Drug: Rituximab Drug: Cyclophosphamide Drug: Mesna Drug: G-CSF Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Bortezomib in Combination With Cyclophosphamide and Rituximab for Relapsed/Refractory Mantle Cell Lymphoma
Study Start Date : August 2009
Actual Primary Completion Date : March 2014
Actual Study Completion Date : March 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Bortezomib with Cyclophosphamide and Rituximab
Bortezomib 1.3 mg/m^2 intravenously (IV) on Days 1, 4, 8, and 11 of the cycle; Cyclophosphamide 300 mg/m^2 IV every 12 hours on Days 2, 3, and 4, and Rituximab 375 mg/m^2 IV on Day 1. Mesna 600 mg/m^2 for 3 days, G-CSF 5 micrograms/kg subcutaneously daily for 7 days after last dose of Bortezomib. Cycles repeated every 21 days for up to six cycles.
Drug: Bortezomib
Bortezomib 1.3 mg/m^2 given intravenously over 3-5 seconds at the end of infusion of Rituximab on Day 1 of every cycle, then on Days 4, 8 and 11 of every cycle.
Other Name: Velcade

Drug: Rituximab
375 mg/m^2 given intravenously over 6-8 hours on Day 1 of every 21-day study cycle.
Other Name: Rituxan

Drug: Cyclophosphamide
300 mg/m^2 intravenously over 3 hours 2 times each day (6 hours total each day) on Days 2, 3, and 4 of every cycle
Other Names:
  • Cytoxan
  • Neosar

Drug: Mesna
600 mg/m^2 intravenous continuous infusion (IVCI) over 24 hours daily for 3 days, 1 hour prior to Cyclophosphamide and complete by 12 hours after last dose of Cyclophosphamide.
Other Name: Mesnex

Drug: G-CSF
5 micrograms/kg subcutaneously daily starting 24-36 hours for 7 days after last dose of Bortezomib until granulocytes are more than 4 x 103/dl.
Other Names:
  • Filgrastim
  • Neupogen
  • Granulocyte-colony stimulating factor
  • GCSF

Primary Outcome Measures :
  1. Response Rate [ Time Frame: Evaluation of disease after 2 cycles (approximately 6 weeks). ]
    Response rate to regimen defined as the percentage of number of complete response or partial response in total number of participants treated. The response assessed after the first 2 cycles. Response (complete and partial remission) according to International Workshop Response Criteria for Non-Hodgkin's Lymphoma: A complete response is the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. A partial response is regression of measurable disease and no new sites of disease. Stable disease is failure to attain a complete response/partial response or progressive disease. A cycle is 21 days with 6-8 cycles administered depending on response.

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Confirmed diagnosis mantle cell lymphoma and its variants, excluding marginal zone and disease exclusively in the GI system. Patients should have measurable disease based on Cheson Criteria or Bone Marrow/tissue sample positive for mantle cell lymphoma. No prior therapy with a combination of bortezomib, cyclophosphamide and rituximab.
  2. Patients with performance status of 2 or less (Zubrod).
  3. Serum bilirubin <1.5 mg/dl and serum creatinine < 2.0 mg/dl unless due to lymphoma; absolute neutrophil count (ANC) >1000/mm^3 and platelets >100,000/mm^3 unless due to lymphoma.
  4. Cardiac ejection fraction 50% or greater.
  5. Ages 18 to 85.
  6. Patients must be willing to receive transfusions of blood products.
  7. Signed consent form.
  8. Voluntary written 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, is surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of contraception (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) from the time of signing the informed consent form through 30 days after the last dose of VELCADE, or agree to completely abstain from heterosexual intercourse.
  10. Male subjects, even if surgically sterilized (ie, status postvasectomy) must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse.

Exclusion Criteria:

  1. Human immunodeficiency virus (HIV) infection.
  2. Central nervous system (CNS) involvement.
  3. Patient has a platelet count of < 100 K (eg <30 x 10^9/L for studies with bortezomib alone) within 14 days before enrollment.
  4. Patient has an absolute neutrophil count of ANC (eg <1.0 x 10^9/L for studies with bortezomib alone)> within 14 days before enrollment.
  5. Patient has > 1.5 times Total Bilirubin
  6. Patient has a calculated or measured creatinine clearance of < 20 mL/minute creatinine clearance (eg <20 mL/minute for studies with bortezomib alone) > within 14 days before enrollment.
  7. Patient has >/= Grade 2 peripheral neuropathy within 14 days before enrollment.
  8. 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.
  9. Patient has hypersensitivity to bortezomib, boron or mannitol.
  10. Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum Beta-human chorionic gonadotropin (Beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
  11. Participation in clinical trials with other investigational agents not included in this trial, within 14 days the start of this trial and throughout the duration of this trial.
  12. Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  13. 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.
  14. Concurrent or previous malignancy whose prognosis is poor (< 90% probability of survival at 5 years).

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): NCT00958256

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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.
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Principal Investigator: Jorge Romaguera, MD M.D. Anderson Cancer Center

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: M.D. Anderson Cancer Center Identifier: NCT00958256     History of Changes
Other Study ID Numbers: 2009-0057
NCI-2009-01577 ( Registry Identifier: NCI CTRP )
First Posted: August 13, 2009    Key Record Dates
Results First Posted: April 13, 2015
Last Update Posted: April 13, 2015
Last Verified: March 2015
Keywords provided by M.D. Anderson Cancer Center:
Mantle Cell Lymphoma
Additional relevant MeSH terms:
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Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Adjuvants, Immunologic
Protective Agents