Chronic Myelogenous LeukemiaPhase 2NCT02709083
Dasatinib or Nilotinib Followed by Imatinib in Patients With Newly Diagnosed, Chronic Phase Chronic Myeloid Leukemia
A Phase 2 study testing Dasatinib, Imatinib Mesylate and Nilotinib in people with Chronic Myelogenous Leukemia and Chronic Myeloid Leukemia, run by Emory University at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 17 years and older
- Conditions the study is for
- Chronic Myelogenous Leukemia, Chronic Myeloid Leukemia, Leukemia
- What is being tested?
- Dasatinib, Imatinib Mesylate and Nilotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2016to Jul 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 17 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Emory University/Winship Cancer Institute
Atlanta, Georgia, 30322
About this study
Official title: First-Line Dasatinib or Nilotinib Followed by Response Guided Switch to Imatinib in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia
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.
Read the detailed description
PRIMARY OBJECTIVE:
- To assess incidence of major molecular response (MMR) at 12 months.
SECONDARY OBJECTIVES:
- 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.
- To assess patient reported outcomes (PRO).
TERTIARY OBJECTIVES:
- 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.
- Being tested
- Dasatinib, Imatinib Mesylate, Nilotinib
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DasatinibDrug
Also called BMS-354825, Sprycel
Given orally
Imatinib MesylateDrug
Also called CGP57148B, Gleevec, Glivec, STI-571
Given orally
NilotinibDrug
Also called AMN 107, Tasigna
Given orally
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Dasatinib; Drug: Imatinib Mesylate; Drug: Nilotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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%).
Measured: At 12 months
Secondary outcomes (7)
Accelerated Phase (AP) or Blast Phase (BP) Free Survival
Survival will be defined as the time from CML diagnosis to the time of transformation to accelerated phase (AP) or blast phase (BP).
Measured: 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)
The patient reported outcomes (PRO) score extracted from the MD Anderson Symptom Inventory (MDASI)-Chronic Myelogenous Leukemia (CML) will be determined and intra and inter subject changes will be compared.
Measured: Baseline to up to 12 months
Duration of Adverse Events (AEs) Using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Criteria
Listings of laboratory test results will also be generated, and descriptive statistics summarizing the changes in laboratory tests over time will be presented. Exposure to drug over time will also be summarized. The AE incidence rates, as well as the frequency of occurrence of overall toxicity, categorized by toxicity grades (severity) will be described as obtained from subject forms and subject communications.
Measured: 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
Listings of laboratory test results will also be generated, and descriptive statistics summarizing the changes in laboratory tests over time will be presented. Exposure to drug over time will also be summarized. The AE incidence rates, as well as the frequency of occurrence of overall toxicity, categorized by toxicity grades (severity) will be described as obtained from subject forms and subject communications.
Measured: Up to 30 days after the end-of-treatment
Progression Free Survival (PFS)
Progression free survival (PFS) will be defined as the time from CML diagnosis to the time of loss of major molecular response (MMR) or loss of hematologic response.
Measured: The time of CML diagnosis to the time of loss of MMR or loss of hematologic response, assessed up to 24 months
Severity of Adverse Events (AEs) Using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Criteria
Listings of laboratory test results will also be generated, and descriptive statistics summarizing the changes in laboratory tests over time will be presented. Exposure to drug over time will also be summarized. The AE incidence rates, as well as the frequency of occurrence of overall toxicity, categorized by toxicity grades (severity) will be described as obtained from subject forms and subject communications.
Measured: Up to 30 days after the end-of-treatment
The Number of Subjects With Breakpoint Cluster Region-abelson Murine Leukemia Viral Oncogene Homolog 1 (BCR-ABL1) Transcript Levels ≤ Deep Molecular Responses (MR⁴)
Descriptive statistics will summarize the changes in breakpoint cluster region-abelson murine leukemia viral oncogene homolog 1 (BCR-ABL1) testing over time will be presented.
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2016 (estimated)
- Study startOct 2016
- Primary completionJul 2018
- Study completionJul 2018
Why it stopped: Original principal investigator left institution
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Myelogenous LeukemiaStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, William Blum, Emory University
- Investigators
- William Blum, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02709083
- Sponsor's protocol ID
- IRB00087045
- Other IDs
- NCI-2016-00162, Winship3143-16
- Status last verified
- Nov 2018
- First submitted
- 10 Mar 2016
- Last updated
- 2 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- First-Line Dasatinib or Nilotinib Followed by Response Guided Switch to Imatinib in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT02709083
- Acronym / sponsor ID
- IRB00087045
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Original principal investigator left institution
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- Oct 2016
- Primary completion
- Jul 2018 (actual)
- Study completion
- Jul 2018 (actual)
- First posted
- 15 Mar 2016 (estimated)
- Results
- Posted 2 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To assess incidence of major molecular response (MMR) at 12 months.
SECONDARY OBJECTIVES:
- 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.
- To assess patient reported outcomes (PRO).
TERTIARY OBJECTIVES:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment-dasatinib, nilotinib, imatinib | Experimental | Drug: Dasatinib, Drug: Imatinib Mesylate, Drug: NilotinibPatients 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. |
Who may qualify
- Ages
- 17 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DasatinibAlso: BMS-354825, SprycelGiven orally | Drug | Treatment-dasatinib, nilotinib, imatinib |
| Imatinib MesylateAlso: CGP57148B, Gleevec, Glivec, STI-571Given orally | Drug | Treatment-dasatinib, nilotinib, imatinib |
| NilotinibAlso: AMN 107, TasignaGiven orally | Drug | Treatment-dasatinib, nilotinib, imatinib |
Primary outcome
The Proportion of Subjects Who Achieve Major Molecular Response (MMR)
Time frame: At 12 months
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%).
7 secondary outcomes
Accelerated Phase (AP) or Blast Phase (BP) Free Survival
Time frame: 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)
Time frame: Baseline to up to 12 months
Duration of Adverse Events (AEs) Using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Criteria
Time frame: 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
Time frame: Up to 30 days after the end-of-treatment
Progression Free Survival (PFS)
Time frame: The time of CML diagnosis to the time of loss of MMR or loss of hematologic response, assessed up to 24 months
Severity of Adverse Events (AEs) Using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Criteria
Time frame: Up to 30 days after the end-of-treatment
The Number of Subjects With Breakpoint Cluster Region-abelson Murine Leukemia Viral Oncogene Homolog 1 (BCR-ABL1) Transcript Levels ≤ Deep Molecular Responses (MR⁴)
Time frame: Up to 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William Blum, MD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dasatinib, Imatinib Mesylate and Nilotinib in people with Chronic Myelogenous Leukemia and Chronic Myeloid Leukemia, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Proportion of Subjects Who Achieve Major Molecular Response (MMR) (time frame: At 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2018.