Study of Bortezomib in Combination With Cyclophosphamide and Rituximab

NCT00958256 | Completed Phase 2 Results

• 3 other identifiers: 2009-0057X05290NCI-2009-01577
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Mantle Cell Lymphoma; Lymphoma

Keywords

Mantle Cell Lymphoma; Lymphoma; Bortezomib; Velcade; Rituximab; Rituxan; Cyclophosphamide; Cytoxan; Neosar; Mesna; Mesnex; G-CSF; Filgrastim; Neupogen

Outcome Measures

Primary Outcomes (1)

• Response Rate

  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.

  Evaluation of disease after 2 cycles (approximately 6 weeks).

Study Arms (1)

Bortezomib with Cyclophosphamide and Rituximab

EXPERIMENTAL

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; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Mesna; Drug: G-CSF

Interventions

Bortezomib DRUG

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.

Also known as: Velcade

Bortezomib with Cyclophosphamide and Rituximab

Rituximab DRUG

375 mg/m\^2 given intravenously over 6-8 hours on Day 1 of every 21-day study cycle.

Also known as: Rituxan

Bortezomib with Cyclophosphamide and Rituximab

Cyclophosphamide DRUG

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

Also known as: Cytoxan, Neosar

Bortezomib with Cyclophosphamide and Rituximab

Mesna DRUG

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.

Also known as: Mesnex

Bortezomib with Cyclophosphamide and Rituximab

G-CSF DRUG

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.

Also known as: Filgrastim, Neupogen, Granulocyte-colony stimulating factor, GCSF

Bortezomib with Cyclophosphamide and Rituximab

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patients with performance status of 2 or less (Zubrod).
• 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.
• Cardiac ejection fraction 50% or greater.
• Ages 18 to 85.
• Patients must be willing to receive transfusions of blood products.
• Signed consent form.
• 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.
• 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.
• 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.

You may not qualify if:

• Human immunodeficiency virus (HIV) infection.
• Central nervous system (CNS) involvement.
• Patient has a platelet count of \< 100 K (eg \<30 x 10\^9/L for studies with bortezomib alone) within 14 days before enrollment.
• 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.
• Patient has \> 1.5 times Total Bilirubin
• 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.
• Patient has \>/= Grade 2 peripheral neuropathy within 14 days before enrollment.
• 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.
• Patient has hypersensitivity to bortezomib, boron or mannitol.
• 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.
• 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.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• 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.
• Concurrent or previous malignancy whose prognosis is poor (\< 90% probability of survival at 5 years).

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Lee HJ, Romaguera JE, Feng L, Desai AP, Zhang L, Fanale M, Samaniego F, Hagemeister FB, Fayad LE, Rodriguez MA, Medeiros JL, Hartig K, Nomie K, Ahmed M, Badillo M, Ye H, Oki Y, Lin P, Nastoupil L, Westin J, Wang M. Phase II Study of Bortezomib in Combination with Cyclophosphamide and Rituximab for Relapsed or Refractory Mantle Cell Lymphoma. Oncologist. 2017 May;22(5):549-553. doi: 10.1634/theoncologist.2016-0328. Epub 2017 Apr 13.

  PMID: 28408615 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Web Site

MeSH Terms

Conditions

Lymphoma, Mantle-Cell; Lymphoma

Interventions

Bortezomib; Rituximab; Cyclophosphamide; Mesna; Granulocyte Colony-Stimulating Factor; Filgrastim

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Results Point of Contact

• Title: Jorge Romaguera, MD/Professor, Lymphoma/Myeloma
• Organization: University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-792-2860

Study Officials

• Jorge Romaguera, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2009
• First Posted: August 13, 2009
• Study Start: August 1, 2009
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: April 13, 2015
• Results First Posted: April 13, 2015

Record last verified: 2015-03

Locations

US (1)