Study Safety and Preliminary Efficacy of DCC-2036 in Patients With Leukemias (Ph+ CML With T315I Mutation)

NCT00827138 | Completed Phase 1

• 1 other identifier: Protocol 2036-01
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 10

Brief Summary

Rationale: DCC-2036 is a potent broad spectrum inhibitor of BCR-ABL kinase. Inhibition of BCR-ABL has been validated for effective treatment of chronic myeloid leukemia (CML). The emergence of mutant forms of BCR-ABL which resist inhibition by imatinib, dasatinib, and nilotinib is associated with loss of efficacy in treatment of the disease. DCC-2036 is a potent inhibitor of resistant mutants of BCR-ABL including the T315I mutation, and would therefore be expected to effectively treat patients who fail to respond to other BCR-ABL inhibitors. DCC-2036 also inhibits FLT3-ITD, TIE2, KDR, LYN and TRKA kinases. Purpose: to assess the safety and tolerability in patients after continuous administration of DCC-2036 and to determine recommended doses for the conduct of a Phase 2 efficacy trial.

Conditions

Chronic Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Assess the safety and tolerability of the drug

  Completion of the study

Secondary Outcomes (1)

• Determine the Pharmacokinetic profile and preliminary evidence of clinical response

  Completion of the study

Study Arms (1)

DCC-2036

EXPERIMENTAL

This is a single arm study

Drug: DCC-2036

Interventions

DCC-2036 DRUG

150 mg BID tablets, continuous dosing of 28 day cycles

Also known as: rebastinib

DCC-2036

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ph+ CML in Chronic Phase with T315I mutation
• years or older
• The subject has an ECOG performance status of ≤ 2.
• Adequate organ function as indicated by the following laboratory assessments performed within 14 days prior to the first dose of study drug Hepatic: Serum bilirubin ≤1.5 times upper limit (X ULN) of normal unless due to leukemic involvement or Gilbert's syndrome; aspartate aminotransferase or alanine aminotransferase ≤ 2.5 X ULN; alkaline phosphatase ≤ 2.5 X ULN Renal: Serum creatinine ≤ 1.5 X ULN or 24 hour creatinine clearance ≥ 50 mL/min
• Female subjects of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin pregnancy test within 14 days prior to the start of study drug
• Sexually active subjects who are fertile must agree to use an effective barrier method of contraception while on therapy and for 30 days following discontinuation of study drug. Non-fertile subjects or those not sexually active are also eligible.
• The subject is capable of understanding and complying with the protocol and has signed the informed consent document.

You may not qualify if:

• Subject has received chemotherapy or a TKI ≤ 7 days, investigational agent ≤ 14 days, or radiotherapy ≤ 28 days prior to the start of study drug or has not recovered from the acute toxicities associated with any prior treatments including approved therapies, investigational agents, and prior stem cell or bone marrow transplant. The following exceptions apply: i) Hydroxyurea is permitted at any time prior to study enrollment; ii) Glucocorticoids (natural or synthetic) are allowed up to 48 hours prior to the start of the study drug (with the exception of steroids for pre-medication and topical/nasal steroid use which are allowed at any time)
• The subject has AP or BP-CML
• Received immunosuppressive therapy ≤ 28 days prior to the first dose of study drug
• NY Heart Association class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart failure
• Myocardial infarction within 3 months of the start of study drug
• Active, uncontrolled systemic infection considered opportunistic, life threatening, or clinically significant
• Any other severe concurrent disease and/or uncontrolled medical conditions, which in the judgment of the investigator, could predispose subjects to unacceptable safety risks or compromise compliance with the protocol
• Human immunodeficiency virus positive
• If female, the subject is pregnant or lactating
• Allergic or hypersensitive to any component of the investigational drug product

Sponsors & Collaborators

• Deciphera Pharmaceuticals, LLC: lead

Study Sites (10)

City of Hope

Duarte, California, 91010, United States

Location

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

The University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

Sidney Kimmel Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (2)

• Cortes J, Talpaz M, Smith HP, Snyder DS, Khoury J, Bhalla KN, Pinilla-Ibarz J, Larson R, Mitchell D, Wise SC, Rutkoski TJ, Smith BD, Flynn DL, Kantarjian HM, Rosen O, Van Etten RA. Phase 1 dose-finding study of rebastinib (DCC-2036) in patients with relapsed chronic myeloid leukemia and acute myeloid leukemia. Haematologica. 2017 Mar;102(3):519-528. doi: 10.3324/haematol.2016.152710. Epub 2016 Dec 7.

  PMID: 27927766 DERIVED

• O'Hare T, Zabriskie MS, Eiring AM, Deininger MW. Pushing the limits of targeted therapy in chronic myeloid leukaemia. Nat Rev Cancer. 2012 Jul 24;12(8):513-26. doi: 10.1038/nrc3317.

  PMID: 22825216 DERIVED

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

DCC-2036; rebastinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jorge Cortes, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

• Hedy P Smith, MD

  Tufts Medical Center

  PRINCIPAL INVESTIGATOR

• Moshe Talpaz, MD

  Univ. of Michigan Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

• Kapil Bhalla, MD

  University of Kansas

  PRINCIPAL INVESTIGATOR

• Richard A Larson, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

• H.Jean Khoury, MD

  Emory University

  PRINCIPAL INVESTIGATOR

• B. Douglas Smith, MD

  Sidney Kimmel Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

• Ehab Atallah, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

• David Snyder, M.D.

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

• Javier Pinilla-Ibarz, MD,PhD

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2009
• First Posted: January 22, 2009
• Study Start: March 1, 2009
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: July 18, 2014

Record last verified: 2014-07

Locations

US (10)