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NCT02098161

LCL161 in Treating Patients With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocytosis Myelofibrosis

Completed Phase 2 Results posted Last updated 6 June 2023
What this trial tests

Phase 2 trial testing Laboratory Biomarker Analysis in Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase in 50 participants. Completed in 19 May 2022.

Timeline
18 December 2014
Primary endpoint
19 May 2022
19 May 2022

Quick facts

Lead sponsorM.D. Anderson Cancer Center
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment50
Start date18 December 2014
Primary completion19 May 2022
Estimated completion19 May 2022
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

M.D. Anderson Cancer Center — full company profile →

Who can join

18 and older, any sex, with Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase or Primary Myelofibrosis. 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.

Number of Participants With a Response Primary · After 3 courses of Therapy

Will be defined as complete remission (CR), partial remission (PR), or clinical improvement (CI) after 3 courses of treatment according to International Working Group (IWG) consensus criteria for myelofibrosis. Complete remission (CR): bone marrow blasts \<5%, hemoglobin \>/= 10, absolute neutrophil count (ANC) \>/= 1000, platelets \>/= 100, \<2% immature myeloid cell, spleen and liver not palpable. Partial Response (PR): CR plus one or more of the following: ANC \>/= 1000, decreased platelets by 50%, hemoglobin \>/= 8.5 but \< 10, \<2% immature myeloid cells. Clinical improvement (CI): hemogl

GroupValue95% CI
Treatment (SMAC Mimetic LCL161)15
Duration of Response Secondary · Up to 7 years 5 Months

duration of response is defined as the date at which the subject's objective status is first noted to be a CR or PR to the date progression is documented (if one has occurred) or to the date of last follow-up (for those subjects who have not progressed).

GroupValue95% CI
Treatment (SMAC Mimetic LCL161)31.53.6 – 59.2
Time to Response Secondary · Up to 7 years 5 months

The time to response is defined as the time from study registration to the first date at which the subject's objective status was classified as a response (CR or PR). In subjects who do not achieve a response, time to response will be censored at the subject's last evaluation date. The distribution for each of these event-time variables (duration of response and time to response) will be estimated by Kaplan-Meier curves.

GroupValue95% CI
Treatment (SMAC Mimetic LCL161)1.40.9 – 9.1
Overall Survival Secondary · Up to 7 years 5 months

Time from date of treatment start until date of death due to any cause or last Follow-up.

GroupValue95% CI
Treatment (SMAC Mimetic LCL161)342.2 – 60.1

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 7 years 5 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment (SMAC Mimetic LCL161)
Serious: 33/50 (66%)
Deaths: 2/50

Serious adverse events (37 terms)

ReactionSystemTreatment (SMAC Mimetic LC…
Lung infectionInfections and infestations
AnemiaBlood and lymphatic system disorders
FeverGeneral disorders
Blood and lymphatic system disordersBlood and lymphatic system disorders
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal hemorrhageGastrointestinal disorders
SyncopeNervous system disorders
Abdominal painGastrointestinal disorders
Chest pain cardiacCardiac disorders
ColitisGastrointestinal disorders
FatigueGeneral disorders
Gastrointestinal disordersGastrointestinal disorders
Platelet count decreasedInvestigations
Respiratory failureRespiratory, thoracic and mediastinal disorders
SepsisInfections and infestations
Surgical and medical proceduresSurgical and medical procedures
Acute kidney injuryRenal and urinary disorders
Allergic reactionImmune system disorders
AnxietyPsychiatric disorders
Atrial fibrillationCardiac disorders
ConfusionPsychiatric disorders
DiarrheaGastrointestinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Erythema multiformeSkin and subcutaneous tissue disorders
FallInjury, poisoning and procedural complications
Other adverse events (54 terms — click to expand)

ReactionSystemTreatment (SMAC Mimetic LC…
FatigueGeneral disorders
NauseaGastrointestinal disorders
PainGeneral disorders
DyspneaRespiratory, thoracic and mediastinal disorders
DiarrheaGastrointestinal disorders
DizzinessNervous system disorders
Rash maculo papularSkin and subcutaneous tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
VomitingGastrointestinal disorders
Edema limbsGeneral disorders
Abdominal distensionGastrointestinal disorders
HeadacheGeneral disorders
InfectionInfections and infestations
FeverGeneral disorders
PruritusSkin and subcutaneous tissue disorders
ConstipationGastrointestinal disorders
Generalized muscle weaknessMusculoskeletal and connective tissue disorders
Weight lossInvestigations
ChillsGeneral disorders
HypotensionVascular disorders
BruisingInjury, poisoning and procedural complications
EpistaxisRespiratory, thoracic and mediastinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
FallInjury, poisoning and procedural complications
MyalgiaMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
InvestigationsInvestigations
AnorexiaMetabolism and nutrition disorders
night sweatsGeneral disorders
Flu like symptomsGeneral disorders
Urinary frequencyRenal and urinary disorders
Surgical and medical proceduresSurgical and medical procedures
Dry skinSkin and subcutaneous tissue disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Postnasal dripRespiratory, thoracic and mediastinal disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders
LightheadednessNervous system disorders
Memory impairmentNervous system disorders
Urinary tract infectionInfections and infestations
MalaiseGeneral disorders

Most-reported serious reactions: Lung infection, Anemia, Fever, Blood and lymphatic system disorders, Neoplasms benign, malignant and unspecified (incl cysts and polyps), Rectal hemorrhage, Syncope, Abdominal pain.

Data from ClinicalTrials.gov NCT02098161 adverse events section.

Sponsor's own description

This phase II trial studies how well second mitochondrial-derived activator of caspases (SMAC) mimetic LCL161 (LCL161) works in treating patients with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocytosis myelofibrosis. SMAC mimetic LCL161 may help control the growth of abnormal cells by promoting apoptosis (programmed cell death).

Publications & conference data

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

  1. Targeting apoptosis in cancer therapy.
    Carneiro BA, El-Deiry WS. · · 2020 · cited 1823× · PMID 32203277 · DOI 10.1038/s41571-020-0341-y
  2. Apoptosis: A Comprehensive Overview of Signaling Pathways, Morphological Changes, and Physiological Significance and Therapeutic Implications.
    Mustafa M, Ahmad R, Tantry IQ, Ahmad W, et al · · 2024 · cited 264× · PMID 39594587 · DOI 10.3390/cells13221838
  3. Mitochondria-associated programmed cell death as a therapeutic target for age-related disease.
    Nguyen TT, Wei S, Nguyen TH, Jo Y, et al · · 2023 · cited 221× · PMID 37612409 · DOI 10.1038/s12276-023-01046-5
  4. Small-molecule SMAC mimetics as new cancer therapeutics.
    Bai L, Smith DC, Wang S. · · 2014 · cited 164× · PMID 24841289 · DOI 10.1016/j.pharmthera.2014.05.007
  5. Small Molecule NF-κB Pathway Inhibitors in Clinic.
    Ramadass V, Vaiyapuri T, Tergaonkar V. · · 2020 · cited 154× · PMID 32708302 · DOI 10.3390/ijms21145164
  6. Future Therapeutic Directions for Smac-Mimetics.
    Morrish E, Brumatti G, Silke J. · · 2020 · cited 108× · PMID 32053868 · DOI 10.3390/cells9020406
  7. Anti-apoptotic proteins in the autophagic world: an update on functions of XIAP, Survivin, and BRUCE.
    Cheung CHA, Chang YC, Lin TY, Cheng SM, et al · · 2020 · cited 77× · PMID 32019552 · DOI 10.1186/s12929-020-0627-5
  8. Management of myelofibrosis after ruxolitinib failure.
    Harrison CN, Schaap N, Mesa RA. · · 2020 · cited 70× · PMID 32198525 · DOI 10.1007/s00277-020-04002-9

Verify or expand the search:

Other trials of Laboratory Biomarker Analysis

Trials testing the same drug.

Other recruiting trials for Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase

Currently open trials in the same condition.

Other M.D. Anderson Cancer Center trials

Trials by the same sponsor.

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Data sources for this page

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