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TerminatedNCT03269552Updated Jan 18, 2020Results posted

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

A Phase 2 interventional study of Carfilzomib and Laboratory Biomarker Analysis in Marginal Zone Lymphoma, Recurrent Marginal Zone Lymphoma and Recurrent Waldenstrom Macroglobulinemia, sponsored by University of Washington. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-01-18.

Sponsored by University of Washington · Phase 2, Interventional, and Treatment

Why this study was terminated
Terminated due to low accrual.
Phase
Phase 2
Study type
Interventional
Enrollment
4
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Marginal Zone Lymphoma
  • Recurrent Marginal Zone Lymphoma
  • Recurrent Waldenstrom Macroglobulinemia
  • Refractory Marginal Zone Lymphoma
  • Refractory Waldenstrom Macroglobulinemia
  • Waldenstrom Macroglobulinemia
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
4 participants (actual)

Study arms

  • 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 · Other: Laboratory Biomarker Analysis · Biological: Rituximab

Interventions

  • DrugCarfilzomib

    Given IV

    Also known as: Kyprolis, PR-171

  • OtherLaboratory Biomarker Analysis

    Correlative studies

  • BiologicalRituximab

    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

05

What researchers measure

Primary outcomes

  1. Overall Response Rate

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

    Time frame: Up to 1 year

Secondary outcomes

  1. Overall Survival

    Estimated using Kaplan-Meier analysis.

    Time frame: Up to 1 year

  2. Time to Best Response

    Estimated using Kaplan-Meier analysis.

    Time frame: Up to 1 year

  3. Time to Progression

    Estimated using Kaplan-Meier analysis.

    Time frame: Up to 1 year

06

Results

Posted Jan 18, 2020
Limitations and caveats
Early termination due to low accrual leading to small number of subjects analyzed.

Participant flow

Participant flow — Overall Study
MilestoneTreatment (Carfilzomib, Rituximab)
Started4
Completed2
Not completed2
Withdrew: Adverse event2

Outcome measures

PrimaryOverall Response Rate

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

Time frame:
Up to 1 year
Reported as:
Count of participants · Participants
Overall Response Rate
ParticipantsTreatment (Carfilzomib, Rituximab)
Complete response0
Very good partial response0
Partial response2
Minor response1
Stable disease1
Progressive disease0
SecondaryOverall Survival

Estimated using Kaplan-Meier analysis.

Time frame:
Up to 1 year
Reported as:
Count of participants · Participants
Overall Survival
ParticipantsTreatment (Carfilzomib, Rituximab)
Overall Survival4
SecondaryTime to Best Response

Estimated using Kaplan-Meier analysis.

Time frame:
Up to 1 year
Reported as:
Median · Months
Time to Best Response
MonthsTreatment (Carfilzomib, Rituximab)
Time to Best Response2 (0.5 to 3)
SecondaryTime to Progression

Estimated using Kaplan-Meier analysis.

Time frame:
Up to 1 year
Reported as:
Median · Months
Time to Progression
MonthsTreatment (Carfilzomib, Rituximab)
Time to Progression8 ± 0.05

Adverse events

Collected over Adverse events are reported from the time the subject receives their first dose of study drug through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Treatment (Carfilzomib, Rituximab)0/4 (0%)1/4 (25%)4/4 (100%)
Most frequent serious events
Most frequent serious events
EventTreatment (Carfilzomib, Rituximab)
Microangiopathic Hemolytic AnemiaBlood and lymphatic system disorders1/4
Most frequent other events
Showing 10 of 25
Most frequent other events
EventTreatment (Carfilzomib, Rituximab)
ChillsGeneral disorders2/4
FatigueGeneral disorders2/4
FlatulanceGastrointestinal disorders2/4
NauseaGastrointestinal disorders2/4
Non-Cardiac Chest PainGeneral disorders2/4
Platelet Count DecreasedInvestigations2/4
AnemiaBlood and lymphatic system disorders1/4
ConstipationGastrointestinal disorders1/4
CoughGeneral disorders1/4
DyspneaRespiratory, thoracic and mediastinal disorders1/4

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Treatment (Carfilzomib, Rituximab)
<=18 years0
Between 18 and 65 years2
>=65 years2
Age, Continuous
Age, Continuous(years)Treatment (Carfilzomib, Rituximab)
Mean64.25 (59 to 69)
Sex: Female, Male
Sex: Female, Male(Participants)Treatment (Carfilzomib, Rituximab)
Female0
Male4
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Treatment (Carfilzomib, Rituximab)
Hispanic or Latino0
Not Hispanic or Latino4
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Treatment (Carfilzomib, Rituximab)
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White4
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)Treatment (Carfilzomib, Rituximab)
United States4
07

Study locations

1 site
  • Fred Hutch/University of Washington Cancer Consortium
    Seattle, Washington 98109, United States
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Oct 2, 2018

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03269552
Lead sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Aug 31, 2017
Start date
Dec 18, 2017
Primary completion
Dec 28, 2018
Completion
Dec 28, 2018
Results posted
Jan 18, 2020
Last update
Jan 18, 2020

Study contacts

Stephen Smith
principal investigator · Fred Hutch/University of Washington Cancer Consortium

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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