Last reviewed · How we verify

NCT03151304

A Safety and Efficacy Study of Pracinostat and Azacitidine in Patients With High Risk Myelodysplastic Syndromes

Terminated Phase 2 Results posted Last updated 2 March 2022
What this trial tests

Phase 2 trial testing Pracinostat in Myelodysplastic Syndromes in 64 participants. Terminated before completion.

Timeline
1 June 2017
Primary endpoint
1 December 2020
1 December 2020

Quick facts

Lead sponsorHelsinn Healthcare SA
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment64
Start date1 June 2017
Primary completion1 December 2020
Estimated completion1 December 2020
Sites25 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Helsinn Healthcare SA — full company profile →

Who can join

18 and older, any sex, with Myelodysplastic Syndromes. 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.

Overall Response Rate (ORR) Primary · 36 months

Percentage of subjects with confirmed complete remission (CR), partial remission (PR) and marrow CR, as per modified International Working Group (IWG) criteria: CR: Bone marrow: ≤5% myeloblasts with normal maturation of all cell lines; Peripheral blood Hemoglobin (Hb) ≥11 g/dL; Platelets ≥100 × 10\^9/L; Neutrophils ≥1.0 × 10\^9/L; Blasts 0%. PR: All CR criteria if abnormal before treatment except: Bone marrow blasts decreased by ≥ 50% over pre-treatment but still \>5%; Cellularity and morphology not relevant Marrow CR: Bone marrow: ≤5% myeloblasts and decrease by ≥50% over pre-treatment

GroupValue95% CI
Stage 1a and 1b Open-label Pracinostat Plus Azacitidine35.924.3 – 48.9
Complete Response (CR) Rate Secondary · 36 months

Percentage of subjects with confirmed CR (i.e., 2 CRs at least 28 days apart) as per modified IWG criteria: CR: Bone marrow: ≤5% myeloblasts with normal maturation of all cell lines; Peripheral blood Hb ≥11 g/dL; Platelets ≥100 × 109/L; Neutrophils ≥1.0 × 109/L; Blasts 0%.

GroupValue95% CI
Stage 1a and 1b Open-label Pracinostat Plus Azacitidine35.924.3 – 48.9
Overall Hematologic Improvement (HI) Response Rate Secondary · 36 months

Percentage of subjects demonstrating major hematologic improvement according to modified IWG: Erythroid response (pre-treatment, \<11 g/dL): Hb increase by ≥1.5 g/dL; Relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 weeks compared with the pre-treatment transfusion number in the previous 8 weeks. Only RBC transfusions given for a Hb of ≤9.0 g/dL pre-treatment will count in the RBC transfusion response evaluation. Platelet response (pre-treatment, \<100 × 10\^9/L): Absolute increase of ≥30 × 10\^9/L for patients starting with \>20 × 10\^9/

GroupValue95% CI
Stage 1a and 1b Open-label Pracinostat Plus Azacitidine71.458.7 – 82.1
Clinical Benefit Rate Secondary · 36 months

Percentage of subjects with confirmed CR, PR, Marrow CR, and HI with clinical benefit rate, defines as rate of CR + PR + HI + Marrow CR. All subjects who achieve hematologic CR, PR, marrow CR, or hematologic improvement on the erythrocytic lineage per modified IWG response criteria will be considered responders

GroupValue95% CI
Stage 1a and 1b Open-label Pracinostat Plus Azacitidine78.166.0 – 87.5
Rate of Cytogenetic CR Secondary · 36 months

Percentage of subjects with confirmed CR by cytogenetic assessment. Complete cytogenetic response is defined per modified IWG response criteria: Complete: Disappearance of the chromosomal abnormality without appearance of new ones Partial: At least 50% reduction of the chromosomal abnormality

GroupValue95% CI
Stage 1a and 1b Open-label Pracinostat Plus Azacitidine46.934.3 – 59.8
Duration of Response (DoR) Secondary · 36 months

For subjects who have achieved CR, PR, Marrow CR, or HI, DoR is defined as the time from the initial determination of response to the time of disease progression or death on study, whichever occurs first.

GroupValue95% CI
Stage 1a and 1b Open-label Pracinostat Plus Azacitidine15.679.00 – 22.11
Rate of Leukemic Transformation Secondary · 6 months

Percentage of subjects with leukemic transformation at landmark time point of 6 months

GroupValue95% CI
Stage 1a and 1b Open-label Pracinostat Plus Azacitidine5.41.8 – 15.8
Event-free Survival (EFS) Secondary · 36 months

time from the first day of study drug administration (Day 1) to failure or death from any cause

GroupValue95% CI
Stage 1a and 1b Open-label Pracinostat Plus Azacitidine17.0511.50 – 21.95
Progression-free Survival (PFS) Secondary · 36 months

time from the first day of study drug administration (Day 1) to disease recurrence or progression as defined by the IWG criteria, or death on study: Disease progression for subjects with: Less than 5% blasts: ≥50% increase in blasts to \>5% blasts 5%-10% blasts: ≥50% increase to \>10% blasts 10%-20% blasts: ≥50% increase to \>20% blasts 20%-30% blasts: ≥50% increase to \>30% blasts Any of the following: At least 50% decrement from maximum remission/response in granulocytes or platelets Reduction in Hb by ≥2 g/dL Transfusion dependence

GroupValue95% CI
Stage 1a and 1b Open-label Pracinostat Plus Azacitidine16.4311.33 – 22.57
Overall Survival (OS) Secondary · form day 1 to death on study, assessed up to 36 months

time from the first day of study drug administration (Day 1) to death on study

GroupValue95% CI
Stage 1a and 1b Open-label Pracinostat Plus Azacitidine23.5616.49 – 30.26
Rate of Leukemic Transformation Secondary · 12 months

Percentage of subjects with leukemic transformation at landmark time point of 12 months

GroupValue95% CI
Stage 1a and 1b Open-label Pracinostat Plus Azacitidine9.53.3 – 25.4
Rate of Leukemic Transformation Secondary · 18 months

Percentage of subjects with leukemic transformation at landmark time point of 18 months

GroupValue95% CI
Stage 1a and 1b Open-label Pracinostat Plus Azacitidine13.85.5 – 32.4

Adverse events — posted to ClinicalTrials.gov

Time frame: All AEs regardless of seriousness or relationship to pracinostat or azacitidine, from the start of study drug treatment until 30 calendar days after discontinuation or completion of treatment as defined by the clinical study for that subject, have been recorded.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Stage 1a and 1b Open-label Pracinostat Plus Azacitidine
Serious: 45/64 (70%)
Deaths: 5/64

Serious adverse events (71 terms)

ReactionSystemStage 1a and 1b Open-label…
Febrile neutropeniaBlood and lymphatic system disorders
PneumoniaInfections and infestations
SepsisInfections and infestations
AnaemiaBlood and lymphatic system disorders
Lung infectionInfections and infestations
PancytopeniaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
PericarditisCardiac disorders
AstheniaGeneral disorders
PresyncopeNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Acute coronary syndromeCardiac disorders
Acute myocardial infarctionCardiac disorders
Atrial fibrillationCardiac disorders
Cardiac failureCardiac disorders
Cardiac failure congestiveCardiac disorders
Pericardial effusionCardiac disorders
Sinus tachycardiaCardiac disorders
Anal fissureGastrointestinal disorders
AscitesGastrointestinal disorders
DysphagiaGastrointestinal disorders
Gastrointestinal haemorrhageGastrointestinal disorders
Haemorrhoidal haemorrhageGastrointestinal disorders
Other adverse events (87 terms — click to expand)

ReactionSystemStage 1a and 1b Open-label…
NauseaGastrointestinal disorders
Neutrophil count decreasedInvestigations
ConstipationGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
FatigueGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
Febrile neutropeniaBlood and lymphatic system disorders
Oedema peripheralGeneral disorders
DiarrhoeaGastrointestinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
DizzinessNervous system disorders
ThrombocytopeniaBlood and lymphatic system disorders
HypoalbuminaemiaMetabolism and nutrition disorders
VomitingGastrointestinal disorders
HypokalaemiaMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
HypotensionVascular disorders
Tongue discolourationGastrointestinal disorders
White blood cell count decreasedInvestigations
HyponatraemiaMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
PyrexiaGeneral disorders
InsomniaPsychiatric disorders
RashSkin and subcutaneous tissue disorders
ContusionInjury, poisoning and procedural complications
FallInjury, poisoning and procedural complications
DehydrationMetabolism and nutrition disorders
AnxietyPsychiatric disorders
AlopeciaSkin and subcutaneous tissue disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
NeutropeniaBlood and lymphatic system disorders
ChillsGeneral disorders
HypocalcaemiaMetabolism and nutrition disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Acute kidney injuryRenal and urinary disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
PneumoniaInfections and infestations
Blood creatinine increasedInvestigations
HyperglycaemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Febrile neutropenia, Pneumonia, Sepsis, Anaemia, Lung infection, Pancytopenia, Thrombocytopenia, Pericarditis.

Data from ClinicalTrials.gov NCT03151304 adverse events section.

Sponsor's own description

This is a Phase 2, two-stage study of the safety and efficacy of pracinostat in combination with azacitidine in patients with IPSS-R high and very high risk myelodysplastic syndrome (MDS) who are previously untreated with hypomethylating agents (HMAs). Enrollment in this study will be limited to high/very high risk MDS because this group represents the highest unmet need, with median survival of less than 18 months. Stage 1a will be conducted as an open-label single arm in up to 40 subjects to assess if this regimen with a lower pracinostat dose results in a discontinuation rate that meets a predefined threshold and in efficacy that justifies expansion of enrollment into Stage 1b. A discontinuation rate of approximately ≤10% in Stage 1a, a rate comparable to that observed with azacitidine alone in study MEI-003 (NCT01873703), supports expansion into Stage 1b. Stage 1b will be conducted as expansion of stage 1a. Approximately 20 additional subjects will be enrolled. Study drugs should be continued until disease progression or intolerable toxicity. It is important to note that the median time to achieving a response with azacitidine alone is 4 to 5 months. Furthermore, the median time to achieving a Complete Response (CR) in study MEI-003 (NCT01873703) was 4 cycles. Therefore, early (\<6 months) discontinuation of trial therapy for 'no response' should be avoided. The Medical Monitor should be contacted prior to discontinuing a subject from the study to discuss the rationale for discontinuation.

Publications & conference data

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

  1. Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials.
    Cheng Y, He C, Wang M, Ma X, et al · · 2019 · cited 760× · PMID 31871779 · DOI 10.1038/s41392-019-0095-0
  2. Epigenetics-targeted drugs: current paradigms and future challenges.
    Dai W, Qiao X, Fang Y, Guo R, et al · · 2024 · cited 131× · PMID 39592582 · DOI 10.1038/s41392-024-02039-0
  3. Recent developments in epigenetic cancer therapeutics: clinical advancement and emerging trends.
    Nepali K, Liou JP. · · 2021 · cited 122× · PMID 33840388 · DOI 10.1186/s12929-021-00721-x
  4. The roles of histone modifications in tumorigenesis and associated inhibitors in cancer therapy.
    Yang Y, Zhang M, Wang Y. · · 2022 · cited 96× · PMID 39036551 · DOI 10.1016/j.jncc.2022.09.002
  5. Targeting epigenetic regulatory machinery to overcome cancer therapy resistance.
    Guo L, Lee YT, Zhou Y, Huang Y. · · 2022 · cited 60× · PMID 33421619 · DOI 10.1016/j.semcancer.2020.12.022
  6. Pharmacological targeting of the cancer epigenome.
    Mabe NW, Perry JA, Malone CF, Stegmaier K. · · 2024 · cited 36× · PMID 38937652 · DOI 10.1038/s43018-024-00777-2
  7. Phase 1 study of belinostat (PXD-101) and bortezomib (Velcade, PS-341) in patients with relapsed or refractory acute leukemia and myelodysplastic syndrome.
    Holkova B, Shafer D, Yazbeck V, Dave S, et al · · 2021 · cited 10× · PMID 33356689 · DOI 10.1080/10428194.2020.1861270
  8. Incorporating novel approaches in the management of MDS beyond conventional hypomethylating agents.
    Odenike O. · · 2017 · cited 5× · PMID 29222294 · DOI 10.1182/asheducation-2017.1.460

Verify or expand the search:

Other trials of Pracinostat

Trials testing the same drug.

Other recruiting trials for Myelodysplastic Syndromes

Currently open trials in the same condition.

Other Helsinn Healthcare SA trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03151304.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing