Phase II Nilotinib With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia (CML)

NCT00129740 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2005-0048NCI-2012-01313
• Study Type: interventional
• Target: 148
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if an experimental agent, AMN107 (nilotinib), can help to control CML in chronic phase. The safety of this experimental agent will also be studied.

Conditions

Leukemia, Myelogenous, Chronic

Keywords

Chronic phase CML; Newly diagnosed chronic phase CML; AMN107

Outcome Measures

Primary Outcomes (1)

• Participants With Complete Molecular Response (Molecular CR)

  Polymerase chain reaction (PCR) Ratio BCR-Abl/Abl of 0% after 12 months of therapy with Nilotinib by international standard.

  12 months

Secondary Outcomes (1)

• Number of Participants With Complete Cytogenetic Response (CCyR)

  6 months

Study Arms (1)

Nilotinib

EXPERIMENTAL

400 mg orally twice daily

Drug: Nilotinib

Interventions

Nilotinib DRUG

400 mg orally twice daily

Also known as: Tasigna®, AMN107

Nilotinib

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Ph-positive or Bcr-positive CML in early chronic phase CML (i.e., time from diagnosis 12 months). Except for hydroxyurea, patients must have received no or minimal prior therapy, defined as \<1 month (30 days) of prior interferon-alpha (with or without cytarabine) and/or an FDA-approved Tyrosine Kinase Inhibitor (TKI). Patients with de novo accelerated phase will be treated but analyzed separately.
• Age \>/= 16 years (Age \>18 years to participate in optional symptom burden assessment)
• Eastern Cooperative Oncology (ECOG) performance of 0-2.
• Adequate end organ function, defined as the following: total bilirubin \< 1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT/SGPT) \< 2.5 x ULN, creatinine \< 1.5 x ULN.
• Patients must sign an informed consent indicating they are aware of the investigational nature of this study, in keeping with the policies of the hospital.
• Reliable telephone access to receive calls from an interactive voice response system (IVR) (only applicable to patients who will participate in optional symptom burden assessment).

You may not qualify if:

• New York Heart Association (NYHA) cardiac class 3-4 heart disease as well as impaired cardiac function defined as: left ventricular ejection fraction (LVEF) \< 45% as determined by Multigated Acquisition Scan (MUGA) scan or electrocardiogram; Complete left bundle branch block; Use of cardiac pacemaker; ST depression of \> 1 mm in 2 or more leads and/or T wave inversions in 2 or more continuous leads; Congenital long QT syndrome; History of, or presence of significant ventricular or atrial tachyarrhythmia's; Clinically significant resting bradycardia (\< 50 bpm); QTc \> 450 msec on screening ECG (using the QTcF formula);
• (Continued from #1) Right bundle branch block plus left anterior hemiblock, bivascular block; Myocardial infarction within 12 months prior to starting AMN107; Unstable angina diagnosed or treated within the past 12 months; Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen).
• Patients with active, uncontrolled psychiatric disorders including: psychosis, major depression, and bipolar disorders.
• Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Surgical sterilization is considered non-childbearing potential. Female patients of reproductive potential must agree to employ an effective method of birth control (hormonal or barrier) throughout the study and for up to 3 months following discontinuation of study drug.
• Patients with severe and/or uncontrolled medial disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection \[persistent fever and worsening clinical condition\]).
• Patient with known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
• Patient with known diagnosis of human immunodeficiency virus (HIV) infection.
• Patients in late chronic phase (i.e., time from diagnosis to treatment \>12 months) or blastic phase are excluded. The definitions of CML phases are as follows: A. Early chronic phase: time from diagnosis to therapy \< 12 months Late chronic phase: time from diagnosis to therapy \> 12 months.B. Blastic phase: presence of 30% blasts or more in the peripheral blood or bone marrow. C. Accelerated phase CML: presence of any of the following features: \* Peripheral or marrow blasts 15% or more.
• (Cont. #8)Peripheral or marrow basophils 20% or more. \*Thrombocytopenia \< 100 x 10(9)/L unrelated to therapy. \* Documented extramedullary blastic disease outside liver or spleen due to past causes D. Clonal evolution defined as the presence of additional chromosomal abnormalities other than the Ph chromosome is part of accelerated phase CML. Ph chromosome variants or complex Ph chromosome translocations are not considered to indicate disease acceleration.
• ( Cont # 8) We have recently found clonal evolution to have a variable prognostic impact and may be suppressed with Interferon therapy (IFN-a therapy). Hence these patients, like others with de novo accelerated phase, will be eligible, and analyzed separately.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Novartis: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (3)

• Jain P, Kantarjian H, Boddu PC, Nogueras-Gonzalez GM, Verstovsek S, Garcia-Manero G, Borthakur G, Sasaki K, Kadia TM, Sam P, Ahaneku H, O'Brien S, Estrov Z, Ravandi F, Jabbour E, Cortes JE. Analysis of cardiovascular and arteriothrombotic adverse events in chronic-phase CML patients after frontline TKIs. Blood Adv. 2019 Mar 26;3(6):851-861. doi: 10.1182/bloodadvances.2018025874.

  PMID: 30885996 DERIVED

• Issa GC, Kantarjian HM, Gonzalez GN, Borthakur G, Tang G, Wierda W, Sasaki K, Short NJ, Ravandi F, Kadia T, Patel K, Luthra R, Ferrajoli A, Garcia-Manero G, Rios MB, Dellasala S, Jabbour E, Cortes JE. Clonal chromosomal abnormalities appearing in Philadelphia chromosome-negative metaphases during CML treatment. Blood. 2017 Nov 9;130(19):2084-2091. doi: 10.1182/blood-2017-07-792143. Epub 2017 Aug 23.

  PMID: 28835440 DERIVED

• Jain P, Kantarjian H, Nazha A, O'Brien S, Jabbour E, Romo CG, Pierce S, Cardenas-Turanzas M, Verstovsek S, Borthakur G, Ravandi F, Quintas-Cardama A, Cortes J. Early responses predict better outcomes in patients with newly diagnosed chronic myeloid leukemia: results with four tyrosine kinase inhibitor modalities. Blood. 2013 Jun 13;121(24):4867-74. doi: 10.1182/blood-2013-03-490128. Epub 2013 Apr 25.

  PMID: 23620574 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase

Interventions

nilotinib

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

Results Point of Contact

• Title: Cortes,Jorge E, MD./Professor
• Organization: The University of Texas MD Anderson Cancer Center

jcortes@mdanderson.org

713-794-5783

Study Officials

• Jorge Cortes, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2005
• First Posted: August 12, 2005
• Study Start: June 27, 2005
• Primary Completion: July 11, 2018
• Study Completion: July 11, 2018
• Last Updated: September 24, 2019
• Results First Posted: September 11, 2019

Record last verified: 2019-09

Locations

US (1)