- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04508790
Leflunomide, Pomalidomide, and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma
A Phase 2 Trial of Leflunomide, Pomalidomide, and Dexamethasone for Relapsed/Refractory Multiple Myeloma
Study Overview
Status
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVE:
I. To estimate the response rate and to evaluate the antitumor activity of the three-drug combination, leflunomide, pomalidomide, and dexamethasone, in patients with relapsed/refractory multiple myeloma.
SECONDARY OBJECTIVES:
I. To characterize and evaluate toxicities, including type, frequency, severity, attribution, time course, and duration.
II. To obtain estimates of response duration, depth of response, clinical benefit, and survival (overall and progression-free).
OUTLINE:
Patients receive leflunomide orally (PO) on days 1-28, pomalidomide PO on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
California
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Duarte, California, United States, 91010
- Recruiting
- City of Hope Medical Center
-
Contact:
- Michael A. Rosenzweig
- Phone Number: 62405 626-256-4973
- Email: mrosenzweig@coh.org
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Principal Investigator:
- Michael A. Rosenzweig
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Documented informed consent of the participant and/or legally authorized representative
- Assent, when appropriate, will be obtained per institutional guidelines
Agreement to allow the use of archival tissue from diagnostic tumor biopsies
- If unavailable, exceptions may be granted with study principal investigator (PI) approval
- Eastern Cooperative Oncology Group (ECOG) =< 2
- Life expectancy > 3 months
Diagnosis of multiple myeloma with measurable disease as defined by:
- M-protein quantities >= 0.5 g/dL by serum protein electrophoresis (sPEP) or
- >= 200 mg/24 hour urine collection by urine protein electrophoresis (uPEP) or
- Serum free light chain (FLC) > 10.0 mg/dL involved light chain and an abnormal kappa/lambda ration in subjects without detectable serum or urine M-protein or
- For subjects with immunoglobulin class A (IgA) myeloma whose disease can only be reliably measured by quantitative immunoglobulin measurement, a serum IgA level >= 0.50 g/dL
- Relapsed or refractory to at least 1 prior line of therapy, including both a proteasome inhibitor and an immunomodulatory drug, and for whom transplant is not recommended. Participants may opt for a delayed transplant at a later time, if appropriate
- Fully recovered from the acute toxic effects (except alopecia) to =< grade 2 to prior anti-cancer therapy
Absolute neutrophil count (ANC) >= 1.0 x 10^9/L (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
- NOTE: Screening ANC should be independent of granulocyte- and granulocyte/macrophage colony stimulating factor (G-CSF and GM-CSF) support for at least 1 week and of pegylated G-CSF for at least 2 weeks
Platelets >= 75.0 x 10^9/L (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
- NOTE: Screening platelet count should be independent of platelet transfusions for at least 2 weeks
Hemoglobin >= 8.0 g/dL (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
- NOTE: Transfusion support is allowed
- Total bilirubin =< 2 X upper limit of normal (ULN) (unless has Gilbert's disease) (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
- Aspartate aminotransferase (AST) =< 3.5 x ULN (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
- Alanine aminotransferase (ALT) =< 3.5 x ULN (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
- Alkaline phosphatase < 5 x ULN (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
- Creatinine clearance of >= 30 mL/min per 24 hour urine test (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
- If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 4 weeks after the last dose of protocol therapy
- Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
Exclusion Criteria:
- Prior treatment with leflunomide
- Patients who are pomalidomide refractory, defined as subjects who progress on or within 60 days of pomalidomide when given as a single agent or in combinatorial therapies. Prior exposure to pomalidomide without refractoriness is allowed
- Current or planned use of other anti-myeloma therapies besides leflunomide, pomalidomide, and dexamethasone
- Current or planned growth factor or transfusion support until after initiation of treatment
- Prior allogeneic transplant
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents
- Positive for tuberculosis or latent tuberculosis (TB)
- Positive for hepatitis A, B, or C
- Known human immunodeficiency virus (HIV) infection
- Prior diagnosis of rheumatoid arthritis
- Acute active infection requiring systemic therapy within 2 weeks prior to enrollment
- Subject has history of anaphylaxis to thalidomide, lenalidomide, pomalidomide, cholestyramine or dexamethasone
Non-hematologic malignancies within the past 3 years, with the exceptions of
- Adequately treated basal cell or squamous cell skin cancer,
- Carcinoma in situ of the cervix,
- Prostate cancer < Gleason grade 6 with stable prostate specific antigen (PSA), or
- Successfully treated in situ carcinoma of the breast
- Females only: Pregnant or breastfeeding
- Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
- Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (leflunomide, pomalidomide, dexamethasone)
Patients receive leflunomide PO on days 1-28, pomalidomide PO on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
Given PO
Other Names:
Given PO
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall response
Time Frame: Up to 1 year
|
Clopper Pearson binomial 95% confidence intervals will be calculated.
|
Up to 1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival
Time Frame: Up to 1 year
|
Will be estimated using the product-limit method of Kaplan and Meier.
|
Up to 1 year
|
Incidence of adverse events
Time Frame: Up to 30 days after last dose
|
Graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.
Observed toxicities will be summarized, for all dose levels, in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.
|
Up to 30 days after last dose
|
Response duration
Time Frame: Up to 1 year
|
Will be estimated using the product-limit method of Kaplan and Meier.
|
Up to 1 year
|
Depth of response
Time Frame: Up to 1 year
|
Will be estimated using the product-limit method of Kaplan and Meier.
|
Up to 1 year
|
Clinical benefit response
Time Frame: Up to 1 year
|
Clopper Pearson binomial 95% confidence intervals will be calculated.
|
Up to 1 year
|
Minimal residual disease (MRD) status
Time Frame: Up to 1 year
|
A patient will be considered as having minimal residual diseases if a positive result is obtained using the Adaptive MRD testing.
MRD testing will be performed at Adaptive Biotechnologies.
|
Up to 1 year
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Michael A Rosenzweig, City of Hope Medical Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Protease Inhibitors
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Dermatologic Agents
- Dexamethasone
- Dexamethasone acetate
- BB 1101
- Pomalidomide
- Leflunomide
- Ichthammol
Other Study ID Numbers
- 19418 (Other Identifier: City of Hope Medical Center)
- NCI-2020-01962 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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