A Phase 1 Dose-escalation Study of a Cell Cycle Inhibitor With and Without Cytarabine in Patients With Acute Leukemias (Study P05247)

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00907517
First received: May 21, 2009
Last updated: September 4, 2014
Last verified: September 2014
  Purpose

This study of SCH 900776 will evaluate its safety and tolerability when given in combination with cytarabine to patients with acute leukemias. Subjects in the Dose-Escalation Part will be enrolled in cohorts that will receive sequentially higher doses of SCH 900776 in combination with standard doses of cytarabine. Only one combination treatment cycle of approximately 4 to 6 weeks is anticipated, but subjects 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 subjects will be studied at the combination-RP2D.


Condition Intervention Phase
Myelogenous Leukemia, Acute
Leukemia, Lymphocytic, Acute
Leukemia, Lymphoblastic, Acute, Philadelphia-Positive
Myelogenous Leukemia, Chronic, Aggressive Phase
Drug: SCH 900776
Drug: Cytarabine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Dose-Escalation Study of SCH 900776 in Combination With Cytarabine in Subjects With Acute Leukemias

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Dose-limiting toxicities and biologic activity used to determine the recommended Phase 2 combination doses of SCH 900776 and cytarabine [ Time Frame: Throughout treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Description of the overall adverse event profile, including any dose-limiting toxicity, of SCH 900776 given alone and in combination with cytarabine [ Time Frame: Throughout treatment up to 45 days after last dose of study medication. ] [ Designated as safety issue: Yes ]

Enrollment: 24
Study Start Date: July 2009
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single arm (various dose cohorts) Drug: SCH 900776
SCH 900776 will be administered to sequential dose cohorts as a 15 minute infusion on Days 2 and 3 and again on Days 11 and 12 in combination with cytarabine. The SCH 900776 starting dose in the Dose-Escalation Part will be 10 mg/m2, and the dose will be doubled with each sequential cohort until 40 mg/m2 is reached, at which point all subsequent dose escalations will occur in 40% increments. If one DLT occurs in Cycle 1 of any dose level, dose escalation will change from dose doubling to 40% increments for the subsequent dose levels.
Drug: Cytarabine
Cytarabine will be administered as continuous intravenous infusion (CIV) at a total dose of 2.0 g/m² over 72 hours (667 mg/m2/24 h) on Days 1-3 and 10-12
Other Names:
  • Generic: ara-C and cytosine arabinoside
  • Cytosar-U®

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject must have a histologically or cytologically confirmed diagnosis of relapsed and/or refractory acute leukemia, including

    • acute myelogenous leukemia, including AML arising from myelodysplasia (MDS) or myeloproliferative disorder (MPD);
    • acute lymphocytic leukemia, including Philadelphia chromosome-positive (Ph+) ALL (Dose-Escalation Part only);
    • chronic myelogenous leukemia (CML) in accelerated phase (AP) or blast crisis (BC) of either myeloid or lymphoid origin (Dose-Escalation Part only);
    • treatment-related high-grade MDS (ie, refractory anemia with excess blasts in transformation [RAEBT]);
    • MPD in transformation [eg, CMMoL-T (5%-19% blasts)].
  • Subject must have recurred or progressed following standard therapy or failed standard therapy, or have disease for which no standard therapy currently exists.
  • Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  • Subject must be 18 years or older, of either sex, and of any race.
  • Subject (and/or parent/guardian for subjects who otherwise is unable to provide independent consent) must be willing to give written informed consent and be able to adhere to dose and visit schedules.
  • Female subject of childbearing potential must have a negative pregnancy test within 5 days prior to first dose of cytarabine.
  • Female subject of childbearing potential and male subject whose sexual partner is of childbearing potential must agree to abstain from sexual intercourse or to use an acceptable method of contraception during the study and for 90 days following the last dose of protocol therapy. Acceptable methods of contraception include condoms (male or female) with or without spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed intrauterine device (IUD), oral or injectable hormonal contraceptive, and surgical sterilization (eg, hysterectomy or tubal ligation).
  • Subject must have adequate renal function as evidenced by a serum creatinine level <=1.5 x upper limit of normal (ULN) or a calculated creatinine clearance >=60 mL/min.
  • Subject, except one with known Gilbert's Syndrome, must have adequate hepatic function as evidenced by a serum bilirubin level <=1.5 mg/dL AND serum levels of aspartate and alanine aminotransferase (AST/ALT) <=5 x the ULN for the reference laboratory.
  • Subject must have adequate cardiac function with a left ventricular ejection fraction (LVEF) of >=45% (echocardiogram or multiple-gated acquisition [MUGA] scan).
  • Subject must be recovered from the effects of any prior surgery, radiotherapy, or systemic antineoplastic therapy.
  • Subject who was refractory to or relapsed after prior allogeneic or autologous stem cell transplant is eligible.

Exclusion Criteria:

  • Subject must not have known hypersensitivity to SCH 900776 or cytarabine or to any of their excipients or have received therapy with another CHK1 inhibitor.
  • Subject must not have received any medication listed below more recently than the indicated washout period prior to first dose of protocol therapy and must not continue to receive treatment that is listed below.
  • Subject must not have persistent, unresolved CTCAE v 3.0 >=Grade 2 drug-related toxicity (except alopecia, erectile impotence, hot flashes, decreased libido, hematologic toxicity) associated with previous treatment.
  • Subject must not have known human immunodeficiency virus (HIV), hepatitis B or hepatitis C, or have a known history of liver cirrhosis or active alcohol abuse.
  • Subject must not be New York Heart Association (NYHA) Class III (has marked limitation in activity due to symptoms, even during less than ordinary activity [eg, walking short distances >20-100 m]; is comfortable only at rest) or Class IV (has severe limitations; experiences symptoms even while at rest; mostly bed bound).
  • Subject must not have any other medical or psychiatric condition that, in the opinion of the investigator, might interfere with the subject's participation in the trial or interfere with the interpretation of trial results.
  • Subject must not have undergone major surgery within 3 weeks prior to first study drug administration after enrollment.
  • Subject must not have known active CNS or leptomeningeal leukemia.
  • Subject must not have received radiation therapy within 2 weeks prior to first study drug administration after enrollment or radiation therapy to >25% of bone marrow.
  • Subject must not have received more than 4 prior induction regimens.
  • Subject must not have a peripheral blast count >=50,000/mm3.
  • Subject must not have active, uncontrolled graft versus host disease (GVHD) post-allogeneic stem cell transplant.
  • Subject must not have had any of the following within 6 months prior to first study drug administration after enrollment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or seizure disorder.
  • Subject must not have a known bleeding diathesis, eg, hemophilia, or disseminated intravascular coagulation.
  • Subject must not have an active, uncontrolled infection.
  • Subject must not have a history of cytarabine-related neurotoxicity.
  • Subject must not have a baseline QTc interval >470 msec (ie, CTCAE v 3.0 Grade >=2).
  • Subject must not currently be a smoker and/or must not be likely to smoke during the study.
  • Female subject must not be breast-feeding, pregnant, or intend to become pregnant.
  • Subject must not be participating in any other interventional clinical study. (Subject participating in another non interventional study may be considered after discussion with the sponsor).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided by Merck Sharp & Dohme Corp.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00907517     History of Changes
Other Study ID Numbers: P05247
Study First Received: May 21, 2009
Last Updated: September 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Accelerated Phase
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Bone Marrow Diseases
Hematologic Diseases
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cytarabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014