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Completed

NCT Number: NCT01593254

Study of Dasatinib vs Imatinib in Patients With Chronic Myeloid Leukemia (CML) Who Did Not Have Favorable Response to Imatinib

The purpose of this study is to test the hypothesis that patients with CML who have not achieved optimal response after 3 months of treatment with imatinib will have a better response by switching to dasatinib compared to staying on their original imatinib regimen.

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Key information

Conditions

Chronic Phase Chronic Myeloid Leukemia Bone Marrow Diseases Chronic Disease Disease Attributes Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid Leukemia, Myeloid, Chronic-Phase Myeloproliferative Disorders Neoplasms Neoplasms by Histologic Type Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Local Institution - 0093, La Plata, Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Chronic Phase (CP)-CML Ph+ patients with complete hematologic response (CHR) but without one log BCR-ABL reduction (BCR-ABL level >10% IS) 3 months of imatinib 400mg treatment. (Imatinib transient dose adjustments due to Adverse Event (AEs) are allowed with a maximum of 2 weeks interruption of treatment with imatinib (cumulative) within the 3 month period before randomization). Imatinib monotherapy must have been started within 6 months of CP-CML diagnosis (Ph + /BCR-ABL detection)
  • Currently tolerating imatinib 400mg QD. Patients with prior imatinib treatment interruption or dose reductions are required to be on treatment with 400 mg imatinib for two weeks immediately prior to randomization to ensure tolerance to imatinib
  • Eastern Co-Operative Group (ECOG) performance status = 0 - 2
  • Adequate renal function defined as serum creatinine ≤3 times the institutional upper limit of normal (ULN)
  • Adequate hepatic function defined as: total bilirubin ≤2.0 times the institutional ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times the institutional ULN

Exclusion criteria

  • Previous diagnosis of accelerated phase or blast crisis
  • Subjects with clonal evolution in Ph+ cells observed in ≥2 metaphases at baseline bone marrow cytogenetic test, unless the same abnormalities were present at diagnosis. Patients with no evidence of clonal evolution, including those patients whose cytogenetic testing fails or bone marrow aspiration is a dry tap at 3 months, are eligible for the study
  • Subjects with less than CHR after 3 months of imatinib treatment or lost CHR after initial achievement
  • Documented T315I/A, F317L, or V299L mutations (if already available - not required for screening)
  • A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy

Treatment and study plan

Imatinib

Drug

Other names: Gleevec, Glivec

dasatinib

Drug

Other names: Sprycel

Primary outcomes

  1. Percentage of Patients Achieving Major Molecular Response (MMR) After 12 Months of CML Treatment

    Time frame: At 12 months after Day 1 initiation of 1st line treatment with imatinib or imatinib at any dose, after less than optimal response to first-line imatinib.

    Major Molecular Response, is defined as a 3-log reduction in BCR-ABL transcripts from the standardized baseline, which represents 100% on the international scale, so a 3-log reduction is fixed at 0.1% for MMR; N/A = not applicable. 95% CI is Clopper-Pearson(Exact) two-sided 95% confidence intervals.

    P-value is based on Cochran-Mantel-Haenszel (CMH) test stratified by Sokal score(high, intermediate, low, and unknown) and time between 3 month molecular analysis and randomization (<=4 weeks vs >4 weeks).

Secondary outcomes

  1. Median Time to Major Molecular Response (MMR)

    Time frame: From randomization to study completion. Approximately 115 months

    Median Time to Major Molecular Response (MMR) is the time between randomization date and first date that MMR (or MR4.5) criteria are satisfied. Participants who do not achieve MMR (or MR4.5) will be censored.

    Major Molecular Response, is defined as a 3-log reduction in BCR-ABL transcripts from the standardized baseline, which represents 100% on the international scale, so a 3-log reduction is fixed at 0.1% for MMR.

  2. Time to Molecular Response (MR)^4.5

    Time frame: From randomization to study completion. Approximately 115 months

    Time to Molecular Response (MR)^4.5 is the time between randomization date and first date that MMR (or MR4.5) criteria are satisfied. Participants who do not achieve MMR (or MR4.5) will be censored.

    MR4.5 is defined as a 4.5-log reduction in BCR-ABL transcript from the standardized baseline (0.0032% IS, either detectable disease <= 0.0032% BCR-ABL (IS) or undetectable disease in cDNA (in same volume used for BCR-ABL) with >= 32,000 ABL transcripts.

  3. Progression Free Survival (PFS)

    Time frame: From randomization to study completion. Approximately 115 months

    PFS is the time from randomization date to progression date or death date, whichever occurs first. Participants who neither progress nor die will be censored.

    Progression is defined as the following, meeting the criteria for accelerated or blast crisis CML are met at any time or death from any cause during treatment.

    Accelerated phase of CML:

    • The presence of ≥15%, but < 30% blasts in the blood or bone marrow
    • At least 30% blasts plus promyelocytes in the blood or bone marrow
    • At least 20% peripheral basophils
    • Thrombocytopenia (fewer than 100,000 platelets/mm3) unrelated to treatment.

    Blast phase of CML

    • At least 30% blasts in the blood or bone marrow
    • Extramedullary involvement (e.g., chloromas), but not hepatosplenomegaly

  4. Overall Survival (OS)

    Time frame: From randomization to study completion. Approximately 115 months

    OS is the time from randomization date to death date. Participants who have not died will be censored on the last date they are known to be alive.

Sponsors and collaborators

Lead sponsor

Bristol-Myers Squibb

Industry

Collaborators

  • Donald E. Morisky
  • ICON Clinical Research
  • MD Anderson Symptom Inventory (MDASI-CML)
  • Molecular MD
  • MultiPharma
  • OBiS, Inc
  • PPD Development, LP
  • Q2 Solutions
  • Steering Committee

Registry information

Official study title

An Open Label, Randomized (2:1) Phase IIb Study of Dasatinib Versus Imatinib in Patients With Chronic Phase Chronic Myeloid Leukemia Who Have Not Achieved an Optimal Response to 3 Months of Therapy With 400 mg Imatinib

Acronym: DASCERN

Important dates

Study start
2012
Primary completion
2017
Study completion
2022
First posted
May 8, 2012
Registry last updated
Jun 22, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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