Bortezomib and Rituximab in Treating Patients With Mantle Cell Lymphoma Who Have Previously Undergone Stem Cell Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by City of Hope Medical Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT01267812
First received: December 27, 2010
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving bortezomib together with rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving bortezomib and rituximab together works in treating patients with mantle cell lymphoma who have previously undergone stem cell transplantation


Condition Intervention Phase
Contiguous Stage II Mantle Cell Lymphoma
Noncontiguous Stage II Mantle Cell Lymphoma
Recurrent Mantle Cell Lymphoma
Stage I Mantle Cell Lymphoma
Stage III Mantle Cell Lymphoma
Stage IV Mantle Cell Lymphoma
Drug: bortezomib
Biological: rituximab
Other: laboratory biomarker analysis
Other: immunohistochemistry staining method
Genetic: RNA analysis
Genetic: gene expression analysis
Genetic: DNA analysis
Other: pharmacological study
Other: pharmacogenomic studies
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Weekly Maintenance Bortezomib and Rituximab in Mantle Cell Lymphoma Post Autologous Hematopoietic Cell Transplantation

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Disease-free survival rate [ Time Frame: At 3 years ] [ Designated as safety issue: No ]
    Assessed by Kaplan-Meier survival analysis. 95% confidence intervals will be calculated using Greenwood's formula.


Secondary Outcome Measures:
  • Overall survival [ Time Frame: Every 6 months for 3 years ] [ Designated as safety issue: No ]
    Assessed by Kaplan-Meier survival analysis. 95% confidence intervals will be calculated using Greenwood's formula.

  • Time to treatment failure [ Time Frame: Every 6 months for 3 years ] [ Designated as safety issue: No ]
    Assessed by Kaplan-Meier survival analysis. 95% confidence intervals will be calculated using Greenwood's formula.

  • Toxicities of bortezomib and rituximab treatment, graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    Observed toxicities will be summarized in terms of type (e.g. organ affected or ANC), severity (by NCI CTCAE and nadir or maximum values for laboratory measures), date of onset, duration, reversibility, and attribution. Tables will be created to summarize these toxicities and side effects.


Estimated Enrollment: 35
Study Start Date: August 2011
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (bortezomib and rituximab)
Patients receive bortezomib SC or IV over 3-5 seconds and rituximab IV on days 1, 8, 15, and 22. Treatment with bortezomib repeats every 3 months for up to 8 courses and treatment with rituximab repeats every 6 months for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Drug: bortezomib
Given SC or IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Other: laboratory biomarker analysis
Correlative studies
Other: immunohistochemistry staining method
Correlative studies
Other Name: immunohistochemistry
Genetic: RNA analysis
Correlative studies
Genetic: gene expression analysis
Correlative studies
Genetic: DNA analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: pharmacogenomic studies
Correlative studies
Other Name: Pharmacogenomic Study

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the two year disease free survival in mantle cell lymphoma (MCL) patients treated with bortezomib + rituximab after hematopoietic stem cell transplantation (HSCT).

SECONDARY OBJECTIVES:

I. To evaluate the toxicity profile, safety, overall survival, time to treatment failure, remission duration, and biological markers of mantle cell lymphoma patients treated with bortezomib + rituximab after autologous hematopoietic stem cell transplantation.

OUTLINE: Patients receive bortezomib subcutaneously (SC) or intravenously (IV) over 3-5 seconds and rituximab IV on days 1, 8, 15, and 22. Treatment with bortezomib repeats every 3 months for up to 8 courses and treatment with rituximab repeats every 6 months for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 3 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histological documented or cytological confirmed mantle cell lymphoma; cyclin D1 must be present as evidenced by either fluorescence in situ hybridization (FISH) or immunohistochemical staining
  • Patients must have undergone autologous hematopoietic stem cell transplantation (AHCT) and achieved engraftment by D60-180 as evidenced by absolute neutrophil count (ANC) > 1000/mcL and platelets (Plt) > 75,000/mcL
  • Patients must be in complete remission at D60-180 after AHCT as evidenced by computed tomography (CT) scan of the neck/chest/abdomen (abd)/pelvis or CT/positron emission tomography (PET) scans
  • Voluntary written informed consent before performance of an 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 or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study
  • Male subject agrees to use an acceptable method for contraception for the duration of the study
  • Life expectancy of greater than 3 months
  • Karnofsky > 60%
  • ANC > 1000/mcL
  • Plts > 75,000/mcL
  • Total bilirubin within normal institutional limits, patients with elevation of unconjugated bilirubin alone, as in Gilbert's disease, are eligible
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 X institutional upper limit of normal
  • Creatinine up to and including 2 mg/dL

Exclusion Criteria:

  • Patient has >= grade 2 peripheral neuropathy within 14 days before enrollment and at D60-180 after AHCT; patients who had >= grade 2 peripheral neuropathy within 14 days before enrollment but resolves to grade 1 or lower peripheral neuropathy at D60-D180 after AHCT can be enrolled at this time
  • Patient has > 1.5 x upper limit of normal (ULN) total bilirubin unless history of Gilbert's syndrome
  • 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 electrocardiographic (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
  • Patient has received other investigational drugs with 14 days before treatment of treatment with bortezomib + rituximab
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study
  • Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy
  • Patients with other active malignancies (no evidence of other cancer or life expectancy greater than 5 years) are ineligible for this study
  • Human immunodeficiency virus (HIV) positive patients or Hepatitis B or C positive patients due to risk of reactivation from marrow-suppressive therapy and Rituximab
  • Patients with active central nervous system (CNS) disease or history of brain metastases (mets) are excluded from study
  • Prior exposure to either bortezomib or rituximab is not an exclusion criteria
  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: NCT01267812

Locations
United States, California
City of Hope Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Robert W. Chen, MD    800-826-4673    rchen@coh.org   
Principal Investigator: Robert W. Chen, MD         
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Leona A. Holmberg, MD    206-667-4832      
Principal Investigator: Leona A. Holmber, MD         
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Robert Chen City of Hope Medical Center
  More Information

No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT01267812     History of Changes
Other Study ID Numbers: 10137, NCI-2010-02343
Study First Received: December 27, 2010
Last Updated: July 14, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

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
Antibodies, Monoclonal
Rituximab
Bortezomib
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 29, 2014