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

NCT01267812 | Completed Phase 2 Results DMC

• 2 other identifiers: 10137NCI-2010-02343
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Two-year Disease-free Survival

  Assessed by Kaplan-Meier survival analysis. 95% confidence intervals will be calculated using Greenwood's formula.

  Participants were followed up to 5 years after initial treatment and Kaplan-Meier survival analysis was used to generate the two-year disease-free survival estimate presented.

Secondary Outcomes (2)

• Two-year Overall Survival

  Participants were followed up to 5 years after initial treatment and Kaplan-Meier survival analysis was used to generate the two-year overall survival estimate presented.

• Grade 3 or 4 Toxicities of Bortezomib and Rituximab Treatment

  Participants were followed up to 5 years after initial treatment.

Study Arms (1)

Treatment (bortezomib and rituximab)

EXPERIMENTAL

Doses of bortezomib given is 1.3 mg/m2 weekly x 4 weeks given every 3 month x 8 cycles. Doses of RITUXAN given is 375 mg/m2 give weekly x 4 weeks given every 6 month for 4 cycles.

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; Other: Questionnaire Administration

Interventions

bortezomib DRUG

Given SC or IV

Also known as: LDP 341, MLN341, VELCADE

Treatment (bortezomib and rituximab)

rituximab BIOLOGICAL

Given IV

Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan

Treatment (bortezomib and rituximab)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (bortezomib and rituximab)

immunohistochemistry staining method OTHER

Correlative studies

Also known as: immunohistochemistry

Treatment (bortezomib and rituximab)

RNA analysis GENETIC

Correlative studies

Treatment (bortezomib and rituximab)

gene expression analysis GENETIC

Correlative studies

Treatment (bortezomib and rituximab)

DNA analysis GENETIC

Correlative studies

Treatment (bortezomib and rituximab)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (bortezomib and rituximab)

pharmacogenomic studies OTHER

Correlative studies

Also known as: Pharmacogenomic Study

Treatment (bortezomib and rituximab)

Questionnaire Administration OTHER

Also known as: Ancillary Studies

Treatment (bortezomib and rituximab)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 day (D)60-180 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 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 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

You may not qualify if:

• 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
• Patients with active central nervous system (CNS) disease or history of brain metastases (mets) are excluded from study

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Chen RW, Palmer JM, Tomassetti S, Popplewell LL, Alluin J, Chomchan P, Nademanee AP, Siddiqi T, Tsai NC, Chen L, Zuo F, Abary R, Cai JL, Herrera AF, Rossi JJ, Rosen ST, Forman SJ, Kwak LW, Holmberg LA. Multi-center phase II trial of bortezomib and rituximab maintenance combination therapy in patients with mantle cell lymphoma after consolidative autologous stem cell transplantation. J Hematol Oncol. 2018 Jun 28;11(1):87. doi: 10.1186/s13045-018-0631-3.

  PMID: 29954415 DERIVED

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

Bortezomib; Rituximab; Immunohistochemistry; Gene Expression Profiling; Pharmacogenomic Testing

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; 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; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Immunologic Techniques; Genetic Techniques; Genetic Testing; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Results Point of Contact

• Title: Dr. Matthew Mei
• Organization: City of Hope

mamei@coh.org

626-359-8111

Study Officials

• Matthew Mei

  City of Hope Medical 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: December 27, 2010
• First Posted: December 29, 2010
• Study Start: October 3, 2011
• Primary Completion: November 2, 2020
• Study Completion: November 2, 2020
• Last Updated: July 27, 2023
• Results First Posted: February 4, 2022

Record last verified: 2023-07

Locations

US (2)