Leflunomide for the Treatment of Severe COVID-19 in Patients With a Concurrent Malignancy
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ClinicalTrials.gov Identifier: NCT04532372 |
Recruitment Status :
Active, not recruiting
First Posted : August 31, 2020
Last Update Posted : December 12, 2022
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Tracking Information | |||||
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First Submitted Date ICMJE | August 25, 2020 | ||||
First Posted Date ICMJE | August 31, 2020 | ||||
Last Update Posted Date | December 12, 2022 | ||||
Actual Study Start Date ICMJE | January 7, 2021 | ||||
Estimated Primary Completion Date | September 18, 2023 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||
Current Other Pre-specified Outcome Measures |
Viral load [ Time Frame: from start of treatment to 90 days ] Measured by PCR assay of viral ribonucleic acid (RNA) from nasopharyngeal swab.
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Original Other Pre-specified Outcome Measures | Same as current | ||||
Descriptive Information | |||||
Brief Title ICMJE | Leflunomide for the Treatment of Severe COVID-19 in Patients With a Concurrent Malignancy | ||||
Official Title ICMJE | A Phase 1/2 Trial of Leflunomide for the Treatment of Severe COVID-19 in Patients With a Concurrent Malignancy | ||||
Brief Summary | This phase I/II trial investigates the best dose and side effects of leflunomide and how well it works in treating patients with COVID-19 and a past or present cancer. Leflunomide has been used since the 1990s as a treatment for rheumatoid arthritis. Experiments done with human cells that were given severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19, showed that leflunomide was able to reduce the ability of the virus to make copies of itself. The coronavirus uses ribonucleic acid (RNA), a very long molecule that contains genetic information that is like a blueprint for making more copies of itself. Leflunomide inhibits the formation of RNA. The information gained from this study may help researchers to learn whether leflunomide is safe for use in treating patients with COVID-19, and whether it is potentially effective against the disease. | ||||
Detailed Description | PRIMARY OBJECTIVES: I. Assess the safety and tolerability of leflunomide when combined with coronavirus disease 2019 (COVID-19) standard of care (SOC) by evaluation of toxicities including: type, frequency, severity, attribution and duration. (Phase 1) II. Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of leflunomide when given in combination with SOC. (Phase 1) III. Evaluate the clinical activity of leflunomide plus SOC (Arm 1) and placebo plus SOC (Arm 2) on the basis of clinical improvement (response) rate in each treatment arm, as assessed by a 7-point ordinal scale. (Phase 2/Pilot) IV. Evaluate the safety and tolerability of leflunomide plus SOC (Arm 1) and placebo plus SOC (Arm2). (Phase 2/Pilot) SECONDARY OBJECTIVES I. Evaluate the clinical activity of leflunomide when combined with SOC on the basis of clinical improvement (response) rate. (Phase 1) II. Estimate the following (Phase 1 and Phase 2): IIa.Time to clinical improvement (days). IIb. Time to peripheral capillary oxygen saturation (SpO2) > 93% on room air (days). IIc. Time to first negative SARS-CoV-2 polymerase chain reaction (PCR) (days). IId. Duration of oxygen therapy (days). IIe. Duration of hospitalization (days). IIf. Duration of mechanical ventilation. IIg. All cause mortality at day 28. III. Measure trough plasma concentrations of the active metabolite teriflunomide on days 1 through 14, day 21, and day 28, and evaluate relationships between teriflunomide levels and pharmacodynamic biomarkers (e.g., viral load, cytokines), response, safety, and concomitant medications. (Phase 1 and Phase 2) EXPLORATORY OBJECTIVES I. Investigate inflammatory response by measuring changes before and after leflunomide treatment in: Ia. Circulating cytokines (e.g., IL-6, IL-8, TNF-alpha, IL-12, interferons [IFNs] and granulocyte-macrophage colony-stimulating factor ([GM-CSF]). Ib. Immune effector cell phenotype associated with monocyte, T cell, and natural killer (NK) cell activation. II. Assess the kinetics of viral replication through serial measurements of viral load by nasopharyngeal swab and tracheal aspirates (if on ventilator and can be safely obtained). OUTLINE: This is a phase I dose-escalation study, followed by a phase II study. PHASE I: Patients receive leflunomide orally (PO) once daily (QD) on days 1-14. Patients may receive SOC drugs in addition to leflunomide. PHASE II: Patients are randomized to 1 of 2 arms. ARM I (LEFLUNOMIDE + SOC): Patients receive leflunomide PO QD on days 1-14. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive SOC. ARM II (PLACEBO + SOC): Patients receive placebo PO QD on days 1-14. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive SOC. After completion of study treatment, patients are followed up for 90 days. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 1 Phase 2 |
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Study Design ICMJE | Allocation: Randomized Intervention Model: Sequential Assignment Intervention Model Description: Phase I single-arm dose-escalation design followed by a phase II randomized two-arm design Masking: Double (Participant, Investigator)Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Active, not recruiting | ||||
Actual Enrollment ICMJE |
2 | ||||
Original Estimated Enrollment ICMJE |
30 | ||||
Estimated Study Completion Date ICMJE | September 18, 2023 | ||||
Estimated Primary Completion Date | September 18, 2023 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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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 | NCT04532372 | ||||
Other Study ID Numbers ICMJE | 20291 NCI-2020-05746 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 20291 ( Other Identifier: City of Hope Comprehensive Cancer Center ) P30CA033572 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | Not Provided | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||
Current Responsible Party | City of Hope Medical Center | ||||
Original Responsible Party | Same as current | ||||
Current Study Sponsor ICMJE | City of Hope Medical Center | ||||
Original Study Sponsor ICMJE | Same as current | ||||
Collaborators ICMJE | National Cancer Institute (NCI) | ||||
Investigators ICMJE |
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PRS Account | City of Hope Medical Center | ||||
Verification Date | December 2022 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |