Bortezomib, Cladribine, and Rituximab in Treating Patients With Advanced Mantle Cell Lymphoma or Indolent Lymphoma

NCT00980395 | Completed Phase 2 Results DMC FDA Drug

• 6 other identifiers: 0800001071P30CA023074UARIZ-08-1071-04X05260CDR000065507808-1071-04
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cladribine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 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 cladribine and rituximab may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving bortezomib together with cladribine and rituximab works in treating patients with advanced mantle cell lymphoma or indolent lymphoma.

Conditions

Lymphoma; Mantle Cell Lymphoma; Indolent Lymphoma; SLL

Keywords

recurrent mantle cell lymphoma; stage III mantle cell lymphoma; stage IV mantle cell lymphoma; recurrent marginal zone lymphoma; stage III marginal zone lymphoma; stage IV marginal zone lymphoma; Waldenstrom macroglobulinemia; recurrent small lymphocytic lymphoma; stage III small lymphocytic lymphoma; stage IV small lymphocytic lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; extranodal marginal zone BCL mucosa assoc lymphoid tissue; nodal marginal zone B Cell lymphoma; splenic marginal zone lymphoma

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival at 2 Years

  PFS was calculated from the first dose of study drug to the first documentation of disease progression, death regardless of cause, or change in therapy due to disease progression, whichever occurred first. If disease progression did not occur by the end of treatment, patients were evaluated every 3 months until progression with physical examination, laboratory studies, and conventional computed tomographic imaging, up to a maximum of 2 years. The Kaplan-Meier product-limit method will be used to estimate progression-free survival in the presence of censoring.

  2 years

Secondary Outcomes (3)

• Overall Survival at 2 Years

  2 years

• Complete Response Rate

  Two years

• Partial Response

  Two years

Study Arms (1)

VCR (Velcade, Cladribine and Rituximab)

EXPERIMENTAL

* Rituximab 375 mg/m2 IV day1 * Cladribine 4 mg/m2 IV over 2 hours days 1-5 * Bortezomib 1.3 mg/m2 IV days 1 and 4 * Repeat every 28 days for a maximum of 6 cycles

Drug: rituximab; Drug: bortezomib; Drug: cladribine

Interventions

rituximab DRUG

375 mg/m2 IV Day 1. Repeat every 28 days for a maximum of 6 cycles.

Also known as: Rituxan

VCR (Velcade, Cladribine and Rituximab)

bortezomib DRUG

1.3 mg/m2 IV Days 1 and 4. Repeat every 28 days for a maximum of 6 cycles.

Also known as: Velcade

VCR (Velcade, Cladribine and Rituximab)

cladribine DRUG

4 mg/m2 IV over 2 hours Days 1-5. Repeat every 28 days for a maximum of 6 cycles.

Also known as: Leustatin

VCR (Velcade, Cladribine and Rituximab)

Eligibility Criteria

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

You may qualify if:

• Voluntary consent before performance of any study-related procedure
• Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control
• Male subject agrees to use an acceptable method for contraception for the duration of the study.
• Biopsy-proven mantle cell, marginal zone, lymphoplasmacytic, small lymphocytic lymphoma, or follicular lymphoma
• CD20-positive disease
• Patients with marginal zone, lymphoplasmacytic, small lymphocytic, or follicular lymphoma - at least one criterion for initiation of treatment must be met:
• Symptomatic disease
• Cytopenia related to lymphoma
• Leukemic phase (\> 5,000 malignant lymphocytes/µl)
• Mass over 5 cm in greatest diameter
• For lymphoplasmacytic lymphoma: additional treatment criteria are serum viscosity ≥ 4 cp, serum monoclonal protein \> 5 g/L, concurrent primary systemic AL amyloidosis, cold agglutinin disease
• Age over 18
• Prior treatment with bortezomib and/or rituximab is acceptable
• For follicular lymphoma only, at least one prior treatment

You may not qualify if:

• Platelet count of \< 100 X10 /L within 14 days before enrollment, unless due to bone marrow infiltration with lymphoma, or due to autoimmune thrombocytopenia because of lymphoma.
• Patient has an absolute neutrophil count of \< 1.0 X 10/L within 14 days before registration, unless due to bone marrow infiltration with lymphoma.
• Patient has a calculated or measured creatinine clearance of \<20 mL/minute within 14 days before registration. (Creatinine Clearance is indicated through the Serum Creatinine. If the Serum Creatinine is abnormal, the physician may then due a 24 hour urine to further clarify Creatinine Clearance. A 24 hour urine test is not required per study.)
• Patient has ≥ Grade 2 peripheral neuropathy within 14 days before registration.
• Myocardial infarction within 6 months prior to registration 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.
• Hypersensitivity to bortezomib, boron or mannitol.
• Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant
• Patient received other investigational drugs with 14 days before registration
• Serious medical or psychiatric illness likely to interfere with study participation
• Diagnosed or treated for another malignancy within 3 years of registration, w/ 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.
• CNS involvement with lymphoma.
• Known HIV-positive.
• History of disease refractory to a purine analog (defined as remission duration of \< 6 months to therapy that included fludarabine, pentostatin, or cladribine).
• History of intolerance of bortezomib, boron, mannitol, cladribine, or rituximab.
• Patient has \> 1.5 X ULN Total Bilirubin

Sponsors & Collaborators

• University of Arizona: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

The University of Arizona Cancer Center

Tucson, Arizona, 85724-5024, United States

Location

Related Publications (1)

• Puvvada SD, Guillen-Rodriguez J, Kumar A, Inclan L, Heard K, Rivera XI, Anwer F, Schatz JH, Mahadevan D, Persky DO. Phase 2 Open-Label Study of Bortezomib, Cladribine, and Rituximab in Advanced, Newly Diagnosed, and Relapsed/Refractory Mantle-Cell and Indolent Lymphomas. Clin Lymphoma Myeloma Leuk. 2018 Jan;18(1):58-64. doi: 10.1016/j.clml.2017.09.001. Epub 2017 Sep 19.

  PMID: 29056470 DERIVED

MeSH Terms

Conditions

Lymphoma; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Waldenstrom Macroglobulinemia; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Follicular

Interventions

Rituximab; Bortezomib; Cladribine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; 2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Amy Selegue, NCTN Program Coordinator
• Organization: University of Arizona

aselegue@email.arizona.edu

520-626-0301

Study Officials

• Daniel O. Persky, MD

  University of Arizona

  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: September 18, 2009
• First Posted: September 21, 2009
• Study Start: July 7, 2009
• Primary Completion: September 12, 2014
• Study Completion: August 14, 2018
• Last Updated: December 30, 2019
• Results First Posted: October 22, 2019

Record last verified: 2019-12

Locations

US (1)