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NCT03094637

Azacitidine and Pembrolizumab in Treating Patients With Myelodysplastic Syndrome

Status unknown Phase 2 Results posted Last updated 22 March 2023
What this trial tests

Phase 2 trial testing Azacitidine in High Risk Myelodysplastic Syndrome in 40 participants. Status unknown.

Timeline
6 November 2017
Primary endpoint
6 November 2021
6 November 2023

Quick facts

Lead sponsorM.D. Anderson Cancer Center
PhasePhase 2
StatusStatus unknown
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment40
Start date6 November 2017
Primary completion6 November 2021
Estimated completion6 November 2023
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 High Risk Myelodysplastic Syndrome or IPSS Risk Category Intermediate-1. 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) Defined as Complete Response + Partial Response + Hematological Improvement Primary · Up to 2 years 4 months

Will estimate the ORR for the experimental treatments, along with the 95% credible intervals. The association between ORR and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.

GroupValue95% CI
Treatment (Azacitidine, Pembrolizumab) in Untreated Patients13
Treatment (Azacitidine, Pembrolizumab) Patients With Hypomethylating Agent (HMA) Failure5
Event Free Survival Primary · Up to 4 years

Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.

GroupValue95% CI
Treatment (Azacitidine, Pembrolizumab) in Untreated Patients9.243.98 – 31.23
Treatment (Azacitidine, Pembrolizumab) Patients With Hypomethylating Agent (HMA) failureHMA Failure5.391.48 – 9.07
Overall Survival Primary · Up to 4 years

Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests. Overall Survival will be presented by median survival, which is the time point at which the cumulative survival drops below 50%. If there is no median survival (not reached), it means the cumulative survival was more than 50%.

GroupValue95% CI
Treatment (Azacitidine, Pembrolizumab) in Untreated PatientsNA1 – 32
Treatment (Azacitidine, Pembrolizumab) Patients With Hypomethylating Agent (HMA) failureHMA Failure5.794.47 – 18.61

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 4 years. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment (Azacitidine, Pembrolizumab) in Untreated Patients
Serious: 9/17 (53%)
Deaths: 1/17
Treatment (Azacitidine, Pembrolizumab) Patients With Hypomethylating Agent (HMA) Failure
Serious: 13/20 (65%)
Deaths: 2/20

Serious adverse events (17 terms)

ReactionSystemTreatment (Azacitidine, Pe…Treatment (Azacitidine, Pe…
InfectionInfections and infestations
Neutropenic FeverBlood and lymphatic system disorders
HyperbilirubinemiaInvestigations
ColitisGastrointestinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
FatigueGeneral disorders
feverGeneral disorders
anemiaBlood and lymphatic system disorders
Hepatobiliary/PancreasHepatobiliary disorders
Infection G 3 or 4 neutrophilsInfections and infestations
Intra-operative InjuryInjury, poisoning and procedural complications
LeukocytesBlood and lymphatic system disorders
NeutrophilsBlood and lymphatic system disorders
PainGeneral disorders
Pruritis/itchingSkin and subcutaneous tissue disorders
Renal/GenitourinaryRenal and urinary disorders
SyncopeNervous system disorders
Other adverse events (15 terms — click to expand)

ReactionSystemTreatment (Azacitidine, Pe…Treatment (Azacitidine, Pe…
NeutropeniaInvestigations
ConstipationGastrointestinal disorders
PainGeneral disorders
Alanine AminotransferaseInvestigations
Asparatate AminotransferaseInvestigations
NauseaGastrointestinal disorders
InfectionInfections and infestations
Rash/desquamationSkin and subcutaneous tissue disorders
Dermatology Skin/OtherSkin and subcutaneous tissue disorders
DiarrheaGastrointestinal disorders
FeverGeneral disorders
anemiaBlood and lymphatic system disorders
Injection Site ReactionGeneral disorders
AnorexiaGastrointestinal disorders
Pruritis/itchingSkin and subcutaneous tissue disorders

Most-reported serious reactions: Infection, Neutropenic Fever, Hyperbilirubinemia, Colitis, Dyspnea, Fatigue, fever, anemia.

Data from ClinicalTrials.gov NCT03094637 adverse events section.

Sponsor's own description

This phase II trial studies the side effects of azacitidine and pembrolizumab and to see how well they work in treating patients with myelodysplastic syndrome. Azacitidine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving azacitidine and pembrolizumab may work better at treating myelodysplastic syndrome.

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. Epigenetic regulation in the tumor microenvironment: molecular mechanisms and therapeutic targets.
    Yang J, Xu J, Wang W, Zhang B, et al · · 2023 · cited 251× · PMID 37217462 · DOI 10.1038/s41392-023-01480-x
  3. Recent advances in targeted therapies in acute myeloid leukemia.
    Bhansali RS, Pratz KW, Lai C. · · 2023 · cited 151× · PMID 36966300 · DOI 10.1186/s13045-023-01424-6
  4. 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
  5. Targeting the Immune Microenvironment in Acute Myeloid Leukemia: A Focus on T Cell Immunity.
    Lamble AJ, Lind EF. · · 2018 · cited 95× · PMID 29951373 · DOI 10.3389/fonc.2018.00213
  6. Novel Approaches to Epigenetic Therapies: From Drug Combinations to Epigenetic Editing.
    Majchrzak-Celińska A, Warych A, Szoszkiewicz M. · · 2021 · cited 85× · PMID 33572577 · DOI 10.3390/genes12020208
  7. Current challenges and unmet medical needs in myelodysplastic syndromes.
    Platzbecker U, Kubasch AS, Homer-Bouthiette C, Prebet T. · · 2021 · cited 67× · PMID 34045662 · DOI 10.1038/s41375-021-01265-7
  8. Targeting PD-1/PD-L1 pathway in myelodysplastic syndromes and acute myeloid leukemia.
    Yang X, Ma L, Zhang X, Huang L, et al · · 2022 · cited 63× · PMID 35236415 · DOI 10.1186/s40164-022-00263-4

Verify or expand the search:

Other trials of Azacitidine

Trials testing the same drug.

Other recruiting trials for High Risk Myelodysplastic Syndrome

Currently open trials in the same condition.

Other M.D. Anderson Cancer Center trials

Trials by the same sponsor.

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