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

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ClinicalTrials.gov Identifier: NCT03269552
Recruitment Status : Recruiting
First Posted : August 31, 2017
Last Update Posted : February 7, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Washington

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. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer 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.

Condition or disease Intervention/treatment Phase
Marginal Zone Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Waldenstrom Macroglobulinemia Refractory Marginal Zone Lymphoma Refractory Waldenstrom Macroglobulinemia Waldenstrom Macroglobulinemia Drug: Carfilzomib Other: Laboratory Biomarker Analysis Biological: Rituximab Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the overall response rate of single-agent weekly carfilzomib (CFZ), measured after 2 cycles of therapy, in Waldenstrom's macroglobulinemia (WM) and marginal zone lymphoma (MZL).

SECONDARY OBJECTIVES:

I. Assess safety and tolerability of single agent, weekly CFZ in patients with WM and MZL, and determine the tolerability of weekly CFZ+rituximab for applicable patients.

II. Estimate the time to best response, response duration, and survival with weekly CFZ for WM and MZL.

III. Evaluate the overall response rate associated with weekly CFZ in a subset of patients with rituximab refractory WM or MZL.

OUTLINE:

Patients receive carfilzomib intravenously (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.

After completion of study treatment, patients are followed up every 3 months for up to 1 year.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Response-Adapted Clinical Trial of Weekly Carfilzomib With or Without Rituximab for Waldenström's Macroglobulinemia and Marginal Zone Lymphoma
Actual Study Start Date : December 18, 2017
Estimated Primary Completion Date : September 15, 2020
Estimated Study Completion Date : September 15, 2020


Arm Intervention/treatment
Experimental: Treatment (carfilzomib, rituximab)
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
Given IV
Other Names:
  • Kyprolis
  • PR-171

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Rituximab
Given IV
Other Names:
  • 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




Primary Outcome Measures :
  1. Overall response rate [ Time Frame: Up to 1 year ]
    Descriptive statistics will be used for baseline characteristics, and responses to treatment.


Secondary Outcome Measures :
  1. Survival outcomes [ Time Frame: Up to 1 year ]
    Estimated using Kaplan-Meier analysis.

  2. Time to best response [ Time Frame: Up to 1 year ]
    Estimated using Kaplan-Meier analysis.

  3. Time to progression [ Time Frame: Up to 1 year ]
    Estimated using Kaplan-Meier analysis.


Other Outcome Measures:
  1. Change in CD19 and CD20 expression following carfilzomib therapy assessed in peripheral blood samples [ Time Frame: Up to 1 year ]
    Changes in mean fluorescence intensity pre- and post-carfilzomib of both CD20 and CD19 will be assessed compared using paired T testing. Peripheral blood samples from each patient before therapy and again after 2 cycles of carfilzomib, will be submitted for quantitative evaluation of CD19 and CD20 surface expression (measuring mean fluorescence intensity).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03269552


Locations
United States, Washington
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Stephen D. Smith    206-606-6546    ssmith50@seattlecca.org   
Principal Investigator: Stephen D. Smith         
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
Investigators
Principal Investigator: Stephen Smith Fred Hutch/University of Washington Cancer Consortium

Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT03269552     History of Changes
Other Study ID Numbers: 9702
NCI-2017-01548 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
9702 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
First Posted: August 31, 2017    Key Record Dates
Last Update Posted: February 7, 2018
Last Verified: February 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell, Marginal Zone
Waldenstrom Macroglobulinemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Antibodies
Immunoglobulins
Rituximab
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Antirheumatic Agents