Study of Bortezomib in Combination With Cyclophosphamide and Rituximab

This study has been completed.
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00958256
First received: August 11, 2009
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

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 Intervention Phase
Mantle Cell Lymphoma
Lymphoma
Drug: Bortezomib
Drug: Rituximab
Drug: Cyclophosphamide
Drug: Mesna
Drug: G-CSF
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Bortezomib in Combination With Cyclophosphamide and Rituximab for Relapsed/Refractory Mantle Cell Lymphoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Response Rate [ Time Frame: Evaluation of disease after 2 cycles. ] [ Designated as safety issue: No ]
    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 cycle is 21 days with 6-8 cycles administered depending on response.


Enrollment: 22
Study Start Date: August 2009
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bortezomib with Cyclophosphamide and Rituximab
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, bortezomib on Days 4 and 8 of every cycle. 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. Rituximab 375 mg/m^2 given intravenously over 6-8 hours on Day 1 of every 21-day study cycle. Mesna 600 mg/m2 in 500- 2000 ml in normal saline (NS) intravenous continuous infusion (IVCI) to run over 24 hours daily for 3 days. 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.
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, bortezomib on Days 4 and 8 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/m2 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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  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: NCT00958256

Locations
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: NCT00958256     History of Changes
Other Study ID Numbers: 2009-0057, X05290
Study First Received: August 11, 2009
Last Updated: June 19, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Mantle Cell Lymphoma
Lymphoma
Bortezomib
Velcade
Rituximab
Rituxan
Cyclophosphamide
Cytoxan
Neosar
Mesna
Mesnex
G-CSF
Filgrastim
Neupogen

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Mesna
Cyclophosphamide
Rituximab
Bortezomib
Lenograstim
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on August 28, 2014