Dasatinib or Nilotinib Followed by Imatinib in Patients With Newly Diagnosed, Chronic Phase Chronic Myeloid Leukemia

NCT02709083 | Terminated Phase 2 Results DMC

• 3 other identifiers: IRB00087045NCI-2016-00162Winship3143-16
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well dasatinib, nilotinib, and imatinib mesylate works in treating patients with newly diagnosed, previously untreated chronic myeloid leukemia in which fewer than 10% of the cells in the blood and bone marrow are blast cells (immature blood cells) (chronic phase). Dasatinib, nilotinib, and imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Chronic Myelogenous Leukemia; Chronic Myeloid Leukemia; Leukemia

Outcome Measures

Primary Outcomes (1)

• The Proportion of Subjects Who Achieve Major Molecular Response (MMR)

  Response will be measured by a decrease in fusion transcript or protein resulting from the 9;22 chromosomal translocation responsible for formation of the Philadelphia Chromosome (BCR-ABL1) levels on a logarithmic scale. A 1 log reduction is a drop to below 10%, while a major molecular response (MMR) is defined as a 3 log reduction (0.1%).

  At 12 months

Secondary Outcomes (7)

• Accelerated Phase (AP) or Blast Phase (BP) Free Survival

  The time of CML diagnosis to the time of transformation to AP or BP, assessed up to 24 months

• Change in Patient Reported Outcomes (PRO) Score Extracted From the MD Anderson Symptom Inventory-Chronic Myelogenous Leukemia (CML)

  Baseline to up to 12 months

• Duration of Adverse Events (AEs) Using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Criteria

  Up to 30 days after the end-of-treatment

• Frequency of Adverse Events (AEs) Using the Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) Criteria

  Up to 30 days after the end-of-treatment

• Progression Free Survival (PFS)

  The time of CML diagnosis to the time of loss of MMR or loss of hematologic response, assessed up to 24 months

Study Arms (1)

Treatment-dasatinib, nilotinib, imatinib

EXPERIMENTAL

Patients receive dasatinib orally (PO) once a day (QD) or nilotinib PO twice a day (BID) at the discretion of the treating hematologist. Patients achieving either a 1 log reduction at 3 months or a 2 log reduction at 6 months in their breakpoint cluster region-abelson murine leukemia viral oncogene homolog 1 (BCR-ABL1) transcript levels may switch to imatinib mesylate PO QD.

Drug: Dasatinib; Drug: Imatinib Mesylate; Drug: Nilotinib

Interventions

Dasatinib DRUG

Given orally

Also known as: BMS-354825, Sprycel

Treatment-dasatinib, nilotinib, imatinib

Imatinib Mesylate DRUG

Given orally

Also known as: CGP57148B, Gleevec, Glivec, STI-571

Treatment-dasatinib, nilotinib, imatinib

Nilotinib DRUG

Given orally

Also known as: AMN 107, Tasigna

Treatment-dasatinib, nilotinib, imatinib

Eligibility Criteria

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

You may qualify if:

• Newly diagnosed, previously untreated chronic phase chronic myeloid leukemia (CP-CML) (by World Health Organization \[WHO\] definition) (hydroxyurea permitted up to 7 days prior to enrollment)
• Clinically significant gastrointestinal disease, digestive dysfunction, or surgery that would compromise absorption of oral administration of medications
• Able to give written informed consent and comply with all study visits and procedures

You may not qualify if:

• Chronic myeloid leukemia (CML) in AP or BP
• Unable to receive TKI for insurance reasons (uninsurable)
• Refuse or unable to perform telephone or video conferences with research coordinator
• Subjects who are pregnant, breast feeding or sexually active and unwilling to use effective birth control while on treatment with TKI
• Any medical or psychological condition that, in the opinion of the investigator, might interfere with the subject's participation in the trial, poses any additional risk for the subject, or confounds the assessment of the subject

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

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

Interventions

Dasatinib; Imatinib Mesylate; nilotinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; 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

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Benzamides; Amides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines

Limitations and Caveats

Trial was terminated early due to original study principal investigator Vamsi Kota, MD, leaving Emory University.

Results Point of Contact

• Title: William Blum, MD
• Organization: Emory University

william.g.blum@emory.edu

404-778-1900

Study Officials

• William Blum, MD

  Emory University

  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: PRINCIPAL INVESTIGATOR
• PI Title: Acting Professor

Study Record Dates

• First Submitted: March 10, 2016
• First Posted: March 15, 2016
• Study Start: October 1, 2016
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: November 2, 2018
• Results First Posted: November 2, 2018

Record last verified: 2018-11

Locations

US (1)