Last reviewed · How we verify

NCT00907517

Study of SCH 900776 (MK-8776) With and Without Cytarabine in Participants With Acute Leukemias (P05247)

Terminated Phase 1 Results posted Last updated 27 August 2018
What this trial tests

Phase 1 trial testing MK-8776 in Myelogenous Leukemia, Acute in 24 participants. Terminated before completion.

Timeline
29 July 2009
Primary endpoint
13 June 2011
13 June 2011

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 1
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment24
Start date29 July 2009
Primary completion13 June 2011
Estimated completion13 June 2011

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Myelogenous Leukemia, Acute or Leukemia, Lymphocytic, Acute. 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 Who Experienced a Dose-limiting Toxicity (DLT) Primary · Throughout Cycle 1 (Up to 6 weeks)

Toxicity was assessed according to the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v 3.0). DLTs in Cycle 1 consisted of any of the following: 1) Selected Grade 4 drug-related nonhematologic toxicities, 2) Selected Grade 3 drug-related nonhematologic toxicities that do not resolve to ≤ Grade 2 within 48 hours: Neurotoxicity of any duration, Nephrotoxicity of any duration, QT interval corrected by Fridericia (QTcF) prolongation of any duration, 3) Inability to administer Day 10 cytarabine therapy due to ongoing, uncontrolled serious or life-threatening toxicity. The number

GroupValue95% CI
MK-8776 10 mg/m^2 + Cytarabine 2 g/m^20
MK-8776 20 mg/m^2 + Cytarabine 2 g/m^20
MK-8776 40 mg/m^2 + Cytarabine 2 g/m^20
MK-8776 56 mg/m^2 + Cytarabine 2 g/m^20
MK-8776 140 mg + Cytarabine 2 g/m^23
Number of Participants Who Experienced an Adverse Event (AE) Primary · Up to 45 days after last dose of study treatment (Up to 180 days)

An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to this study treatment. The number of participants who experienced an AE is summarized.

GroupValue95% CI
MK-8776 10 mg/m^2 + Cytarabine 2 g/m^23
MK-8776 20 mg/m^2 + Cytarabine 2 g/m^23
MK-8776 40 mg/m^2 + Cytarabine 2 g/m^26
MK-8776 56 mg/m^2 + Cytarabine 2 g/m^26
MK-8776 140 mg + Cytarabine 2 g/m^26
Number of Participants Who Discontinued Study Treatment Due to an AE Primary · Up to 135 days

An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to this study treatment. The number of participants who discontinued study treatment due to an AE is summarized.

GroupValue95% CI
MK-8776 10 mg/m^2 + Cytarabine 2 g/m^20
MK-8776 20 mg/m^2 + Cytarabine 2 g/m^20
MK-8776 40 mg/m^2 + Cytarabine 2 g/m^20
MK-8776 56 mg/m^2 + Cytarabine 2 g/m^20
MK-8776 140 mg + Cytarabine 2 g/m^20

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 45 days after last dose of study treatment (Up to 180 days). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

MK-8776 10 mg/m^2 + Cytarabine 2 g/m^2
Serious: 0/3 (0%)
Deaths:
MK-8776 20 mg/m^2 + Cytarabine 2 g/m^2
Serious: 0/3 (0%)
Deaths:
MK-8776 40 mg/m^2 + Cytarabine 2 g/m^2
Serious: 1/6 (17%)
Deaths:
MK-8776 56 mg/m^2 + Cytarabine 2 g/m^2
Serious: 2/6 (33%)
Deaths:
MK-8776 140 mg + Cytarabine 2 g/m^2
Serious: 1/6 (17%)
Deaths:

Serious adverse events (12 terms)

ReactionSystemMK-8776 10 mg/m^2 + Cytara…MK-8776 20 mg/m^2 + Cytara…MK-8776 40 mg/m^2 + Cytara…MK-8776 56 mg/m^2 + Cytara…MK-8776 140 mg + Cytarabin…
FEBRILE NEUTROPENIABlood and lymphatic system disorders
GASTRITISGastrointestinal disorders
NAUSEAGastrointestinal disorders
VOMITINGGastrointestinal disorders
FUNGAL INFECTIONInfections and infestations
PNEUMONIAInfections and infestations
PNEUMONIA FUNGALInfections and infestations
SUBDURAL HAEMATOMAInjury, poisoning and procedural complications
HEADACHENervous system disorders
RENAL FAILURE ACUTERenal and urinary disorders
PULMONARY OEDEMARespiratory, thoracic and mediastinal disorders
HYPERTENSIONVascular disorders
Other adverse events (164 terms — click to expand)

ReactionSystemMK-8776 10 mg/m^2 + Cytara…MK-8776 20 mg/m^2 + Cytara…MK-8776 40 mg/m^2 + Cytara…MK-8776 56 mg/m^2 + Cytara…MK-8776 140 mg + Cytarabin…
FEBRILE NEUTROPENIABlood and lymphatic system disorders
NAUSEAGastrointestinal disorders
HYPERTENSIONVascular disorders
DIARRHOEAGastrointestinal disorders
VOMITINGGastrointestinal disorders
MUCOSAL INFLAMMATIONGeneral disorders
BLOOD ALKALINE PHOSPHATASE INCREASEDInvestigations
FATIGUEGeneral disorders
TRANSFUSION REACTIONInjury, poisoning and procedural complications
ALANINE AMINOTRANSFERASE INCREASEDInvestigations
ASPARTATE AMINOTRANSFERASE INCREASEDInvestigations
BLOOD CREATININE INCREASEDInvestigations
HYPOKALAEMIAMetabolism and nutrition disorders
HEADACHENervous system disorders
INSOMNIAPsychiatric disorders
RASHSkin and subcutaneous tissue disorders
ANAEMIABlood and lymphatic system disorders
NEUTROPENIABlood and lymphatic system disorders
PERICARDIAL EFFUSIONCardiac disorders
CONJUNCTIVAL HAEMORRHAGEEye disorders
ABDOMINAL PAINGastrointestinal disorders
CONSTIPATIONGastrointestinal disorders
HAEMORRHOIDSGastrointestinal disorders
OEDEMA PERIPHERALGeneral disorders
PYREXIAGeneral disorders
HYPERBILIRUBINAEMIAHepatobiliary disorders
CANDIDIASISInfections and infestations
PNEUMONIAInfections and infestations
ELECTROCARDIOGRAM QT PROLONGEDInvestigations
DECREASED APPETITEMetabolism and nutrition disorders
HYPERGLYCAEMIAMetabolism and nutrition disorders
HYPERPHOSPHATAEMIAMetabolism and nutrition disorders
HYPOALBUMINAEMIAMetabolism and nutrition disorders
HYPOCALCAEMIAMetabolism and nutrition disorders
ARTHRALGIAMusculoskeletal and connective tissue disorders
PAIN IN EXTREMITYMusculoskeletal and connective tissue disorders
ANXIETYPsychiatric disorders
HAEMATURIARenal and urinary disorders
EPISTAXISRespiratory, thoracic and mediastinal disorders
NASAL CONGESTIONRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: FEBRILE NEUTROPENIA, GASTRITIS, NAUSEA, VOMITING, FUNGAL INFECTION, PNEUMONIA, PNEUMONIA FUNGAL, SUBDURAL HAEMATOMA.

Data from ClinicalTrials.gov NCT00907517 adverse events section.

Sponsor's own description

This study of SCH 900776 (MK-8776) will evaluate its safety and tolerability when given in combination with cytarabine to participants with acute leukemias. Participants in the Dose-Escalation Part will be enrolled in cohorts that will receive sequentially higher doses of MK-8776 in combination with standard doses of cytarabine. Only one combination treatment cycle of approximately 4 to 6 weeks is anticipated, but participants may receive additional cycles if clinically indicated after discussion between the Investigator and the Sponsor. The recommended combination doses for a Phase 2 trial (RP2D) will be determined based on safety and biological activity. Up to 10 to 15 additional participants will be studied at the combination RP2D.

Publications & conference data

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

  1. Cell cycle proteins as promising targets in cancer therapy.
    Otto T, Sicinski P. · · 2017 · cited 1412× · PMID 28127048 · DOI 10.1038/nrc.2016.138
  2. ATR/CHK1 inhibitors and cancer therapy.
    Qiu Z, Oleinick NL, Zhang J. · · 2018 · cited 282× · PMID 29054375 · DOI 10.1016/j.radonc.2017.09.043
  3. DNA Repair Pathways in Cancer Therapy and Resistance.
    Li LY, Guan YD, Chen XS, Yang JM, et al · · 2020 · cited 254× · PMID 33628188 · DOI 10.3389/fphar.2020.629266
  4. Targeting DNA damage response in cancer therapy.
    Hosoya N, Miyagawa K. · · 2014 · cited 232× · PMID 24484288 · DOI 10.1111/cas.12366
  5. Targeting the DNA Damage Response in OSCC with TP53 Mutations.
    Lindemann A, Takahashi H, Patel AA, Osman AA, et al · · 2018 · cited 117× · PMID 29489434 · DOI 10.1177/0022034518759068
  6. Phase I and pharmacologic trial of cytosine arabinoside with the selective checkpoint 1 inhibitor Sch 900776 in refractory acute leukemias.
    Karp JE, Thomas BM, Greer JM, Sorge C, et al · · 2012 · cited 95× · PMID 23092873 · DOI 10.1158/1078-0432.ccr-12-2442
  7. TNBC: Potential Targeting of Multiple Receptors for a Therapeutic Breakthrough, Nanomedicine, and Immunotherapy.
    Singh DD, Yadav DK. · · 2021 · cited 76× · PMID 34440080 · DOI 10.3390/biomedicines9080876
  8. Prospects for the Use of ATR Inhibitors to Treat Cancer.
    Wagner JM, Kaufmann SH. · · 2010 · cited 42× · PMID 27713304 · DOI 10.3390/ph3051311

Verify or expand the search:

Other trials of MK-8776

Trials testing the same drug.

Other Merck Sharp & Dohme LLC 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/NCT00907517.

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