Clinical trial NCT02709083: Dasatinib or Nilotinib Followed by Imatinib in Patients With Newly Diagnosed, Chronic Phase Chronic Myeloid Leukemia
Official title: First-Line Dasatinib or Nilotinib Followed by Response Guided Switch to Imatinib in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Myelogenous Leukemia
Chronic Myeloid Leukemia
Leukemia
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2016-03-15
Enrollment: 7
Sex: ALL
Minimum age (years): 17
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: PRIMARY OBJECTIVE:

I. To assess incidence of major molecular response (MMR) at 12 months.

SECONDARY OBJECTIVES:

I. To assess progression free survival (PFS) at 12 and 24 months.

II. To assess accelerated phase (AP) or blast phase (BP) transformation-free survival at 12 and 24 months.

III. To assess incidence of deep MRs (≥ MR⁴) at 12 months and 24 months.

IV. To assess safety.

V. To assess patient reported outcomes (PRO).

TERTIARY OBJECTIVES:

I. To assess prognostic significance of detecting aberrant myeloid or lymphoid markers on diagnostic bone marrow.

II. To assess ability to enroll subjects who maintain deep molecular remissions in tyrosine kinase inhibitors (TKIs) discontinuation trials.

OUTLINE:

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.

After completion of study treatment, patients are followed up at 2 weeks and then up to 60 months.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: The Proportion of Subjects Who Achieve Major Molecular Response (MMR)
timeFrame: At 12 months
Secondary outcomes:
measure: Accelerated Phase (AP) or Blast Phase (BP) Free Survival
timeFrame: The time of CML diagnosis to the time of transformation to AP or BP, assessed up to 24 months
measure: Change in Patient Reported Outcomes (PRO) Score Extracted From the MD Anderson Symptom Inventory-Chronic Myelogenous Leukemia (CML)
timeFrame: Baseline to up to 12 months
measure: Duration of Adverse Events (AEs) Using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Criteria
timeFrame: Up to 30 days after the end-of-treatment
measure: Frequency of Adverse Events (AEs) Using the Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) Criteria
timeFrame: Up to 30 days after the end-of-treatment
measure: Progression Free Survival (PFS)
timeFrame: The time of CML diagnosis to the time of loss of MMR or loss of hematologic response, assessed up to 24 months
measure: Severity of Adverse Events (AEs) Using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Criteria
timeFrame: Up to 30 days after the end-of-treatment
measure: The Number of Subjects With Breakpoint Cluster Region-abelson Murine Leukemia Viral Oncogene Homolog 1 (BCR-ABL1) Transcript Levels ≤ Deep Molecular Responses (MR⁴)
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University/Winship Cancer Institute
state: Georgia
Study officials:
affiliation: Emory University
name: William Blum, MD
role: PRINCIPAL_INVESTIGATOR
References: