Carfilzomib With or Without Rituximab in the Treatment of Waldenstrom Macroglobulinemia or Marginal Zone Lymphoma

NCT03269552 | Terminated Phase 2 Results DMC FDA Drug

• 4 other identifiers: 9702NCI-2017-01548P30CA015704RG1716046
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well carfilzomib with or without rituximab work in treating patients with Waldenstrom macroglobulinemia or marginal zone lymphoma that is previously untreated, has come back, or does not respond to treatment. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as rituximab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving carfilzomib alone when disease is responding or with rituximab when disease is not responding may work better in treating patients with Waldenstrom macroglobulinemia or marginal zone lymphoma.

Conditions

Marginal Zone Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Waldenstrom Macroglobulinemia; Refractory Marginal Zone Lymphoma; Refractory Waldenstrom Macroglobulinemia; Waldenstrom Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Descriptive statistics will be used for baseline characteristics, and responses to treatment.

  Up to 1 year

Secondary Outcomes (3)

• Overall Survival

  Up to 1 year

• Time to Best Response

  Up to 1 year

• Time to Progression

  Up to 1 year

Study Arms (1)

Treatment (carfilzomib, rituximab)

EXPERIMENTAL

Patients receive carfilzomib IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who fail to achieve at least 25% M-protein reduction for Waldenstrom's macroglobulinemia or partial response for marginal zone lymphoma after 2 courses of carfilzomib, receive rituximab IV weekly on days 1, 8, 15, and 22 of course 3 and then monthly on day 1 of courses 4-6 in the absence of disease progression or unacceptable toxicity.

Drug: Carfilzomib; Other: Laboratory Biomarker Analysis; Biological: Rituximab

Interventions

Carfilzomib DRUG

Given IV

Also known as: Kyprolis, PR-171

Treatment (carfilzomib, rituximab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (carfilzomib, rituximab)

Rituximab BIOLOGICAL

Given IV

Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, RTXM83

Treatment (carfilzomib, rituximab)

Eligibility Criteria

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

You may qualify if:

• Waldenstrom's macroglobulinemia (WM) or marginal zone lymphoma (MZL) based on institutional pathology review; patients may have either previously untreated or relapsed/refractory disease
• Measurable disease: for WM presence of monoclonal IgM immunoglobulin concentration on serum electrophoresis, with lymphoplasmacytic marrow infiltrate; for MZL: measurable nodal disease measuring at least 1.5 cm in longest dimension, or splenomegaly
• Indication for initiation of therapy
• Absolute neutrophil count (ANC) \> 1,000/uL unless disease-related (due to marrow infiltration or splenomegaly)
• Platelet count \> 75,000/uL unless disease-related (due to marrow infiltration or splenomegaly)
• Serum creatinine \< 2.5 mg/dL or creatinine clearance \> 30 cc/min
• Bilirubin \< 2 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 x ULN
• All patients must be informed of the investigational nature of this study and have given written consent in accordance with institutional and federal guidelines
• Expected survival of \> 90 days
• Females of childbearing potential (FCBP) must agree to pregnancy testing and to practice contraception
• Male subjects must agree to practice contraception

You may not qualify if:

• Known human immunodeficiency virus (HIV), hepatitis C, or hepatitis B positivity (subjects with hepatitis B surface antigen \[SAg\] or core antibody positivity, who are receiving and responding to antiviral therapy directed at hepatitis B or are negative for hepatitis B virus \[HBV\] deoxyribonucleic acid \[DNA\], are allowed)
• Candidate for potentially curative antibiotic therapy for gastric mucosa-associated lymphoid tissue (MALT); (gastric MALT lymphoma patients with stage I/II helicobacter \[H.\] pylori positive lymphoma must fail therapy with H.-pylori directed therapy before being considered for this study)
• Eastern Cooperative Oncology Group (ECOG) performance status 3 or higher
• Known active central nervous system (CNS) involvement
• Pregnant or lactating females
• Inadequate cardiac function, as measured by left ventricular ejection fraction (LVEF) that is less than or equal to 40%, or the presence of New York Heart Association (NYHA) classification of greater than stage II congestive heart failure
• Significant neuropathy (grades 3-4, or grade 2 with pain) within 14 days prior to screening
• Uncontrolled inter-current illness including, but not limited to, unstable angina, recent myocardial infarction within 6 months of screening and uncontrolled cardiac arrhythmias, psychiatric illness, or psychosocial difficulty that would limit compliance with study requirements
• Non-hematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study

Sponsors & Collaborators

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

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone; Waldenstrom Macroglobulinemia

Interventions

carfilzomib; Rituximab; CT-P10

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Early termination due to low accrual leading to small number of subjects analyzed.

Results Point of Contact

• Title: Dr. Stephen Smith
• Organization: University of Washington

ssmith50@seattlecca.org

206-606-6546

Study Officials

• Stephen Smith

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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 29, 2017
• First Posted: August 31, 2017
• Study Start: December 18, 2017
• Primary Completion: December 28, 2018
• Study Completion: December 28, 2018
• Last Updated: January 18, 2020
• Results First Posted: January 18, 2020

Record last verified: 2020-01

Locations

US (1)