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

NCT ID: NCT01773408

Last Updated: 2017-01-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 122 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2016-06-30

Brief Summary

This Phase 1/1b, open-label study will evaluate the safety and pharmacokinetics of escalating doses of RO5503781 as a single agent or in combination with cytarabine in participants with acute myelogenous leukemia. In Part 1, RO5503781 will be administered in escalating doses as a single agent, and in Part 2, RO5503781 will be administered in combination with cytarabine. An optional Part 3 in which RO5503781 will be 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.

Conditions

Myelogenous Leukemia, Acute

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: RO5503781

Participants will receive RO5503781 alone in escalating doses on Days 1 to 5 of each 28-day cycle until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

RO5503781 MBP

Intervention Type: DRUG

Participants will receive RO5503781 tablets daily (current formulation) containing microprecipitated bulk powder (MBP) at a starting dose of 400 milligrams (mg).

Part 2: RO5503781 + Cytarabine

Participants will receive RO5503781 in escalating doses on Days 1 to 5 and cytarabine on Days 1 to 6 of each 28-day cycle until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

RO5503781 MBP

Intervention Type: DRUG

Participants will receive RO5503781 tablets daily (current formulation) containing microprecipitated bulk powder (MBP) at a starting dose of 400 milligrams (mg).

Cytarabine

Intervention Type: DRUG

Parts 2 and 4: Participants will receive cytarabine 1000 milligrams per meter squared (mg/m\^2) intravenous (IV) infusion daily. Part 3: Participants will receive cytarabine 100-200 mg/m\^2 IV infusion daily.

Part3:RO5503781+Cytarabine+Anthracycline

Participants will receive RO5503781 on Days 1 to 5, cytarabine on Days 1 to 7, and anthracycline (daunorubicin or idarubicin) on Days 1 to 3 of each 28-day cycle until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

RO5503781 MBP

Intervention Type: DRUG

Participants will receive RO5503781 tablets daily (current formulation) containing microprecipitated bulk powder (MBP) at a starting dose of 400 milligrams (mg).

Idarubicin

Intervention Type: DRUG

Idarubicin will be administered as per standard clinical practice.

Daunorubicin

Intervention Type: DRUG

Daunorubicin will be administered as per standard clinical practice.

Cytarabine

Intervention Type: DRUG

Parts 2 and 4: Participants will receive cytarabine 1000 milligrams per meter squared (mg/m\^2) intravenous (IV) infusion daily. Part 3: Participants will receive cytarabine 100-200 mg/m\^2 IV infusion daily.

Part 4: Optimized RO5503781 + Cytarabine

Participants will receive optimized RO5503781 formulation on Days 1 to 5 and cytarabine on Days 1 to 6 of each 28-day cycle until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

RO5503781 SDP

Intervention Type: DRUG

Participants will receive RO5503781 tablets daily (new optimized formulation) containing spray-dried powder (SDP) at recommended dose(s) for development from Phase 1b to Phase 3.

Cytarabine

Intervention Type: DRUG

Parts 2 and 4: Participants will receive cytarabine 1000 milligrams per meter squared (mg/m\^2) intravenous (IV) infusion daily. Part 3: Participants will receive cytarabine 100-200 mg/m\^2 IV infusion daily.

Interventions

RO5503781 MBP

Participants will receive RO5503781 tablets daily (current formulation) containing microprecipitated bulk powder (MBP) at a starting dose of 400 milligrams (mg).

Intervention Type: DRUG

RO5503781 SDP

Participants will receive RO5503781 tablets daily (new optimized formulation) containing spray-dried powder (SDP) at recommended dose(s) for development from Phase 1b to Phase 3.

Intervention Type: DRUG

Idarubicin

Idarubicin will be administered as per standard clinical practice.

Intervention Type: DRUG

Daunorubicin

Daunorubicin will be administered as per standard clinical practice.

Intervention Type: DRUG

Cytarabine

Parts 2 and 4: Participants will receive cytarabine 1000 milligrams per meter squared (mg/m\^2) intravenous (IV) infusion daily. Part 3: Participants will receive cytarabine 100-200 mg/m\^2 IV infusion daily.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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, participants 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 National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade less than or equal to (</=) 2 prior to starting therapy
• Adequate hepatic and renal function
• Willing to submit the blood sampling and bone marrow sampling required by protocol

Exclusion Criteria

• Participants 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
• Participants with severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
• Participants with evidence of electrolyte imbalance greater than or equal to (>/=) Grade 2 which cannot be corrected prior to study initiation
• Pregnant or breastfeeding women
• Human immunodeficiency virus (HIV) - positive participants receiving anti-retroviral therapy
• Participants who refuse to potentially receive blood products and/or have a hypersensitivity to blood products

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

USC Norris Cancer Center

Los Angeles, California, United States

New York Medical College

Valhalla, New York, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Cancer Therapy & Research Ctr; Dept Institute for Drug Development

San Antonio, Texas, United States

Peter Maccallum Cancer Centre

Melbourne, Victoria, Australia

University Health Network; Princess Margaret Hospital; Medical Oncology Dept

Toronto, Ontario, Canada

McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology

Montreal, Quebec, Canada

Institut J Paoli I Calmettes; Onco Hematologie 2

Marseille, , France

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpigh

Bologna, Emilia-Romagna, Italy

Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

The Beatson West of Scotland Cancer Centre; Cancer Clinical Trials Unit

Glasgow, , United Kingdom

Countries

United States; Australia; Canada; France; Italy; South Korea; United Kingdom

References

Yee K, Papayannidis C, Vey N, Dickinson MJ, Kelly KR, Assouline S, Kasner M, Seiter K, Drummond MW, Yoon SS, Lee JH, Blotner S, Jukofsky L, Pierceall WE, Zhi J, Simon S, Higgins B, Nichols G, Monnet A, Muehlbauer S, Ott M, Chen LC, Martinelli G. Murine double minute 2 inhibition alone or with cytarabine in acute myeloid leukemia: Results from an idasanutlin phase 1/1b study small star, filled. Leuk Res. 2021 Jan;100:106489. doi: 10.1016/j.leukres.2020.106489. Epub 2020 Dec 1.

Reference Type: DERIVED

PMID: 33302031 (View on PubMed)

Other Identifiers

2012-004882-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NP28679

Identifier Type: -

Identifier Source: org_study_id