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Trial record 5 of 82 for:    abp 798

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03269552
Recruitment Status : Terminated (Terminated due to low accrual.)
First Posted : August 31, 2017
Results First Posted : January 18, 2020
Last Update Posted : January 18, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Washington

Tracking Information
First Submitted Date  ICMJE August 29, 2017
First Posted Date  ICMJE August 31, 2017
Results First Submitted Date  ICMJE December 2, 2019
Results First Posted Date  ICMJE January 18, 2020
Last Update Posted Date January 18, 2020
Actual Study Start Date  ICMJE December 18, 2017
Actual Primary Completion Date December 28, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 29, 2017)
Overall Response Rate [ Time Frame: Up to 1 year ]
Descriptive statistics will be used for baseline characteristics, and responses to treatment.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 8, 2020)
  • Overall Survival [ Time Frame: Up to 1 year ]
    Estimated using Kaplan-Meier analysis.
  • Time to Best Response [ Time Frame: Up to 1 year ]
    Estimated using Kaplan-Meier analysis.
  • Time to Progression [ Time Frame: Up to 1 year ]
    Estimated using Kaplan-Meier analysis.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 29, 2017)
  • Survival outcomes [ Time Frame: Up to 1 year ]
    Estimated using Kaplan-Meier analysis.
  • Time to Best Response [ Time Frame: Up to 1 year ]
    Estimated using Kaplan-Meier analysis.
  • Time to Progression [ Time Frame: Up to 1 year ]
    Estimated using Kaplan-Meier analysis.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: August 29, 2017)
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).
 
Descriptive Information
Brief Title  ICMJE Carfilzomib With or Without Rituximab in the Treatment of Waldenstrom Macroglobulinemia or Marginal Zone Lymphoma
Official Title  ICMJE A Response-Adapted Clinical Trial of Weekly Carfilzomib With or Without Rituximab for Waldenström's Macroglobulinemia and Marginal Zone Lymphoma
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Marginal Zone Lymphoma
  • Recurrent Marginal Zone Lymphoma
  • Recurrent Waldenstrom Macroglobulinemia
  • Refractory Marginal Zone Lymphoma
  • Refractory Waldenstrom Macroglobulinemia
  • Waldenstrom Macroglobulinemia
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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.
Interventions:
  • Drug: Carfilzomib
  • Other: Laboratory Biomarker Analysis
  • Biological: Rituximab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 9, 2019)
4
Original Estimated Enrollment  ICMJE
 (submitted: August 29, 2017)
24
Actual Study Completion Date  ICMJE December 28, 2018
Actual Primary Completion Date December 28, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03269552
Other Study ID Numbers  ICMJE 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 )
RG1716046 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Washington
Study Sponsor  ICMJE University of Washington
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Stephen Smith Fred Hutch/University of Washington Cancer Consortium
PRS Account University of Washington
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP