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A Study of RO5503781 as Single Agent or in Combination With Cytarabine in Patients With Acute Myelogenous Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01773408
First received: January 18, 2013
Last updated: October 3, 2016
Last verified: October 2016
  Purpose
This phase I/IB, open-label study will evaluate the safety and pharmacokinetics of escalating doses of RO5503781 as single agent or in combination with cytarabine in patients with acute myelogenous leukemia. An optional Part 3 in which RO5503781 is administered with cytarabine and anthracycline may be considered. In Part 4, the safety and pharmacokinetic profile of an optimized formulation of RO5503781 in combination with cytarabine will be assessed.

Condition Intervention Phase
Myelogenous Leukemia, Acute
Drug: RO5503781 MDP
Drug: RO5503781 SDP
Drug: anthracycline
Drug: cytarabine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A MULTI-CENTER, OPEN-LABEL, PHASE 1/1B STUDY OF ESCALATING DOSES OF RO5503781 ADMINISTERED ORALLY AS 1) A SINGLE AGENT, 2) IN COMBINATION WITH CYTARABINE, OR 3) WITH CYTARABINE AND ANTHRACYCLINE AND 4) ASSESSING PK AND SAFETY OF NEW OPTIMIZED FORMULATION OF RO5503781 WITH CYTARABINE IN PATIENTS WITH ACUTE MYELOGENOUS LEUKEMIA (AML)

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) [ Time Frame: approximately 1.5 years ] [ Designated as safety issue: No ]
  • Dose-limiting toxicities (DLTs) [ Time Frame: approximately 1.5 years ] [ Designated as safety issue: No ]
  • Safety: Incidence of adverse events [ Time Frame: approximately 1.5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Efficacy: Complete remission [ Time Frame: approximately 1.5 years ] [ Designated as safety issue: No ]
  • Efficacy: Partial Response [ Time Frame: approximately 1.5 years ] [ Designated as safety issue: No ]
  • Efficacy: Disease progression [ Time Frame: approximately 1.5 years ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Plasma concentrations of RO5503781 alone and in combination with cytarabine [ Time Frame: first 28-day cycle ] [ Designated as safety issue: No ]
  • Pharmacodynamics: Leukemia-related biomarkers [ Time Frame: first 28-day cycle ] [ Designated as safety issue: No ]
  • Efficacy: Hematologic malignancy response [ Time Frame: approximately 1.5 years ] [ Designated as safety issue: No ]

Enrollment: 122
Study Start Date: February 2013
Study Completion Date: June 2016
Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1: RO5503781 Drug: RO5503781 MDP
multiple escalating doses, current formulation
Drug: anthracycline
anthracycline per standard clinical practice
Experimental: Part 2: RO5503781 + Cytarabine Drug: RO5503781 MDP
multiple escalating doses, current formulation
Drug: anthracycline
anthracycline per standard clinical practice
Drug: cytarabine
1000 mg/m2 iv daily for 6 days each cycle
Experimental: Part 3: RO5503781 + Cytarabine + Anthracycline Drug: anthracycline
anthracycline per standard clinical practice
Experimental: Part 4: Optimized Formulation + Cytarabine Drug: RO5503781 SDP
recommended phase 2 dose, new optimized formulation
Drug: cytarabine
1000 mg/m2 iv daily for 6 days each cycle

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients, >/= 18 years of age
  • Documented/confirmed acute myelogenous leukemia (AML), except for acute promyelocytic leukemia
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 in Part 1 and Part 2, patients enrolled in the extension/tail portion, Part 3 and Part 4 must have an ECOG performance status of 0 or 1
  • All non-hematological adverse events of any prior chemotherapy, surgery or radiotherapy must have resolved to NCI-CTCAE Grade </=2 prior to starting therapy
  • Adequate hepatic and renal function
  • Willing to submit the blood sampling and bone marrow sampling required by protocol Additional inclusion criteria for Parts 1-4 may apply.

Exclusion Criteria:

  • Patients receiving any other investigational or commercial agents or therapies administered with the intention to treat their malignancy within 14 days of first receipt of study drug, with the exception of hydroxyurea as defined in protocol
  • History of allergic or toxic reactions attributed to cytarabine (Part 2) or history of allergic reactions to components of the formulated product
  • Current evidence of central nervous system (CNS) leukemia
  • Patients with severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
  • Patients with evidence of electrolyte imbalance of Grade >/= 2 which cannot be corrected prior to study initiation
  • Pregnant or breastfeeding women
  • HIV-positive patients receiving anti-retroviral therapy
  • Patients who refuse to potentially receive blood products and/or have a hypersensitivity to blood products Additional exclusion criteria for Parts 1-4 may apply.
  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.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01773408

Locations
United States, California
Los Angeles, California, United States, 90033
United States, New York
Valhalla, New York, United States, 10595
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19107
United States, Texas
Houston, Texas, United States, 77030
San Antonio, Texas, United States, 78229
Australia, Victoria
Melbourne, Victoria, Australia, 3000
Canada, Ontario
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Montreal, Quebec, Canada, H3T 1E2
France
Marseille, France, 13273
Italy
Bologna, Emilia-Romagna, Italy, 40138
Korea, Republic of
Seoul, Korea, Republic of, 03080
Seoul, Korea, Republic of, 05505
United Kingdom
Glasgow, United Kingdom, G12 0YN
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01773408     History of Changes
Other Study ID Numbers: NP28679  2012-004882-41  RG7388 
Study First Received: January 18, 2013
Last Updated: October 3, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 07, 2016