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NCT02509052

Leflunomide in Treating Patients With Relapsed or Refractory Multiple Myeloma

Completed Phase 1, PHASE2 Results posted Last updated 10 October 2023
What this trial tests

Phase 1, PHASE2 trial testing Laboratory Biomarker Analysis in Recurrent Plasma Cell Myeloma in 12 participants. Completed in 9 June 2022.

Timeline
2 December 2015
Primary endpoint
18 September 2018
9 June 2022

Quick facts

Lead sponsorCity of Hope Medical Center
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment12
Start date2 December 2015
Primary completion18 September 2018
Estimated completion9 June 2022
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

City of Hope Medical Center

Who can join

18 and older, any sex, with Recurrent Plasma Cell Myeloma or Refractory Plasma Cell Myeloma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

MTD, Defined as the Highest Dose in Which =< 1/6 Patients Experience a Dose-limiting Toxicity, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 Primary · 28 days

Observed toxicities will be summarized, for all dose levels, in terms of type (organ affected or laboratory determination), severity, time of onset, duration, serum concentration of the active leflunomide metabolite, probable association with the study treatment and reversibility or outcome.

GroupValue95% CI
All Participants60
Best Overall Response Rate: Proportion of Patients Reaching CR by IMWG Criteria Primary · From the start of treatment until disease progression/recurrence, assessed up to 48 months

Stringent complete response \[sCR\]/complete response \[CR\]/very good partial response \[VGPR\]/or partial response \[PR\]), assessed by International Myeloma Working Group (IMWG) criteria.

GroupValue95% CI
Arm 1: 20 mg Leflunomide3
Arm 2: 40 mg Leflunomide3
Arm 3: 60 mg Leflunomide3
Clinical Benefit Response Rate (sCR/CR/VGPR/Partial Response [PR]/Minimal Response [MR] or Stable Disease [SD]), Assessed by IMWG Criteria Secondary · From the start of treatment until disease progression/recurrence, assessed up to 48 months

Clinical benefit response rate (sCR/CR/VGPR/partial response \[PR\]/minimal response \[MR\] or stable disease \[SD\]), assessed by International Myeloma Working Group (IMWG) criteria

GroupValue95% CI
Arm 1: 20 mg Leflunomide3
Arm 2: 40 mg Leflunomide3
Arm 3: 60 mg Leflunomide3
Response Duration Secondary · Assessed up to 48 months

Median and range of nine patients with Complete Response (CR)

GroupValue95% CI
Arm 1: 20 mg Leflunomide33628 – 401
Arm 2: 40 mg Leflunomide11291 – 152
Arm 3: 60 mg Leflunomide5428 – 56
Response Duration Secondary · Assessed at ninety days.

Number of patients with Stable Disease greater than or equal to 90 days

GroupValue95% CI
Arm 1: 20 mg Leflunomide2
Arm 2: 40 mg Leflunomide3
Arm 3: 60 mg Leflunomide0

Adverse events — posted to ClinicalTrials.gov

Time frame: up to thirty days post-treatment.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm 1: 20 mg Leflunomide
Serious: 1/3 (33%)
Deaths: 0/3
Arm 2: 40 mg Leflunomide
Serious: 2/3 (67%)
Deaths: 2/3
Arm 3: 60 mg Leflunomide
Serious: 4/6 (67%)
Deaths: 2/6

Serious adverse events (8 terms)

ReactionSystemArm 1: 20 mg LeflunomideArm 2: 40 mg LeflunomideArm 3: 60 mg Leflunomide
10016558-FeverGeneral disorders
10040047-SepsisInfections and infestations
10046571-Urinary tract infectionInfections and infestations
10061229-Lung infectionInfections and infestations
10017076-FractureInjury, poisoning and procedural complications
10003481-Aspartate aminotransferase increasedInvestigations
10003988-Back painMusculoskeletal and connective tissue disorders
10023838-Laryngeal edemaRespiratory, thoracic and mediastinal disorders
Other adverse events (87 terms — click to expand)

ReactionSystemArm 1: 20 mg LeflunomideArm 2: 40 mg LeflunomideArm 3: 60 mg Leflunomide
10035528-Platelet count decreasedInvestigations
10020772-HypertensionVascular disorders
10016256-FatigueGeneral disorders
10002646-AnorexiaMetabolism and nutrition disorders
10040752-Sinus tachycardiaCardiac disorders
10016558-FeverGeneral disorders
10033371-PainGeneral disorders
10046571-Urinary tract infectionInfections and infestations
10029366-Neutrophil count decreasedInvestigations
10049182-White blood cell decreasedInvestigations
10020943-HypoalbuminemiaMetabolism and nutrition disorders
10021018-HypokalemiaMetabolism and nutrition disorders
10021038-HyponatremiaMetabolism and nutrition disorders
10028411-MyalgiaMusculoskeletal and connective tissue disorders
10000081-Abdominal painGastrointestinal disorders
10010774-ConstipationGastrointestinal disorders
10012727-DiarrheaGastrointestinal disorders
10028813-NauseaGastrointestinal disorders
10047700-VomitingGastrointestinal disorders
10008531-ChillsGeneral disorders
10011368-Creatinine increasedInvestigations
10047900-Weight lossInvestigations
10012174-DehydrationMetabolism and nutrition disorders
10020949-HypocalcemiaMetabolism and nutrition disorders
10021005-HypoglycemiaMetabolism and nutrition disorders
10021059-HypophosphatemiaMetabolism and nutrition disorders
10003239-ArthralgiaMusculoskeletal and connective tissue disorders
10016750-Flank painMusculoskeletal and connective tissue disorders
10033425-Pain in extremityMusculoskeletal and connective tissue disorders
10013573-DizzinessNervous system disorders
10010300-ConfusionPsychiatric disorders
10022437-InsomniaPsychiatric disorders
10019450-HematuriaRenal and urinary disorders
10046539-Urinary frequencyRenal and urinary disorders
10011224-CoughRespiratory, thoracic and mediastinal disorders
10028735-Nasal congestionRespiratory, thoracic and mediastinal disorders
10021097-HypotensionVascular disorders
10025182-Lymph node painBlood and lymphatic system disorders
10033557-PalpitationsCardiac disorders
10061389-Tricuspid valve diseaseCardiac disorders

Most-reported serious reactions: 10016558-Fever, 10040047-Sepsis, 10046571-Urinary tract infection, 10061229-Lung infection, 10017076-Fracture, 10003481-Aspartate aminotransferase increased, 10003988-Back pain, 10023838-Laryngeal edema.

Data from ClinicalTrials.gov NCT02509052 adverse events section.

Sponsor's own description

This phase I/II trial studies the side effects and best dose of leflunomide in treating patients with multiple myeloma that has come back (relapsed) or has not responded to previous treatment (refractory). Leflunomide may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Nucleotide metabolism: a pan-cancer metabolic dependency.
    Mullen NJ, Singh PK. · · 2023 · cited 308× · PMID 36973407 · DOI 10.1038/s41568-023-00557-7
  2. Drug repurposing for cancer therapy.
    Xia Y, Sun M, Huang H, Jin WL. · · 2024 · cited 229× · PMID 38637540 · DOI 10.1038/s41392-024-01808-1
  3. Mitochondrial adaptation in cancer drug resistance: prevalence, mechanisms, and management.
    Jin P, Jiang J, Zhou L, Huang Z, et al · · 2022 · cited 180× · PMID 35851420 · DOI 10.1186/s13045-022-01313-4
  4. DHODH and cancer: promising prospects to be explored.
    Zhou Y, Tao L, Zhou X, Zuo Z, et al · · 2021 · cited 133× · PMID 33971967 · DOI 10.1186/s40170-021-00250-z
  5. The emergence of dihydroorotate dehydrogenase (DHODH) as a therapeutic target in acute myeloid leukemia.
    Sykes DB. · · 2018 · cited 77× · PMID 30318938 · DOI 10.1080/14728222.2018.1536748
  6. Multiple Sclerosis and Cancer: The Ying-Yang Effect of Disease Modifying Therapies.
    Melamed E, Lee MW. · · 2019 · cited 56× · PMID 31998289 · DOI 10.3389/fimmu.2019.02954
  7. Targeting miRNAs and Other Non-Coding RNAs as a Therapeutic Approach: An Update.
    Bayraktar E, Bayraktar R, Oztatlici H, Lopez-Berestein G, et al · · 2023 · cited 51× · PMID 37104009 · DOI 10.3390/ncrna9020027
  8. Small-molecule agents for cancer immunotherapy.
    Wang F, Fu K, Wang Y, Pan C, et al · · 2024 · cited 41× · PMID 38486980 · DOI 10.1016/j.apsb.2023.12.010

Verify or expand the search:

Other trials of Laboratory Biomarker Analysis

Trials testing the same drug.

Other recruiting trials for Recurrent Plasma Cell Myeloma

Currently open trials in the same condition.

Other City of Hope Medical Center trials

Trials by the same sponsor.

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