Chronic Myeloid LeukemiaPhase 1NCT00827138
Study Safety and Preliminary Efficacy of DCC-2036 in Patients With Leukemias (Ph+ CML With T315I Mutation)
A Phase 1 study testing DCC-2036 in people with Chronic Myeloid Leukemia, run by Deciphera Pharmaceuticals, LLC at 10 sites in United States.
Trial summary
Rationale: DCC-2036 is a potent broad spectrum inhibitor of BCR-ABL kinase. Inhibition of BCR-ABL has been validated for effective treatment of chronic myeloid leukemia (CML). The emergence of mutant forms of BCR-ABL which resist inhibition by imatinib, dasatinib, and nilotinib is associated with loss of efficacy in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Myeloid Leukemia
- What is being tested?
- DCC-2036
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 10 sitesUnited States
- Study dates
- Mar 2009to Jan 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Inclusion Criteria: Subjects must meet all of the following inclusion criteria to be eligible:
- Ph+ CML in Chronic Phase with T315I mutation
- 18 years or older
- The subject has an ECOG performance status of ≤ 2.
- Adequate organ function as indicated by the following laboratory assessments performed within 14 days prior to the first dose of study drug Hepatic: Serum bilirubin ≤1.5 times upper limit (X ULN) of normal unless due to leukemic involvement or Gilbert's syndrome; aspartate aminotransferase or alanine aminotransferase ≤ 2.5 X ULN; alkaline phosphatase ≤ 2.5 X ULN Renal: Serum creatinine ≤ 1.5 X ULN or 24 hour creatinine clearance ≥ 50 mL/min
- Female subjects of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin pregnancy test within 14 days prior to the start of study drug
- Sexually active subjects who are fertile must agree to use an effective barrier method of contraception while on therapy and for 30 days following discontinuation of study drug. Non-fertile subjects or those not sexually active are also eligible.
- The subject is capable of understanding and complying with the protocol and has signed the informed consent document.
Exclusion Criteria: Subjects presenting with any of the following will not qualify for entry into the study:
- Subject has received chemotherapy or a TKI ≤ 7 days, investigational agent ≤ 14 days, or radiotherapy ≤ 28 days prior to the start of study drug or has not recovered from the acute toxicities associated with any prior treatments including approved therapies, investigational agents, and prior stem cell or bone marrow transplant. The following exceptions apply: i) Hydroxyurea is permitted at any time prior to study enrollment; ii) Glucocorticoids (natural or synthetic) are allowed up to 48 hours prior to the start of the study drug (with the exception of steroids for pre-medication and topical/nasal steroid use which are allowed at any time)
- The subject has AP or BP-CML
- Received immunosuppressive therapy ≤ 28 days prior to the first dose of study drug
- NY Heart Association class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart failure
- Myocardial infarction within 3 months of the start of study drug
- Active, uncontrolled systemic infection considered opportunistic, life threatening, or clinically significant
- Any other severe concurrent disease and/or uncontrolled medical conditions, which in the judgment of the investigator, could predispose subjects to unacceptable safety risks or compromise compliance with the protocol
- Human immunodeficiency virus positive
- If female, the subject is pregnant or lactating
- Allergic or hypersensitive to any component of the investigational drug product
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
Emory University
Atlanta, Georgia, 30322
Sidney Kimmel Cancer Center at Johns Hopkins
Baltimore, Maryland, 21287
Tufts Medical Center
Boston, Massachusetts, 02111
University of Chicago
Chicago, Illinois, 60637
City of Hope
Duarte, California, 91010
MD Anderson Cancer Center
Houston, Texas, 77030
The University of Kansas Cancer Center
Kansas City, Kansas, 66160
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612
About this study
Official title: A Multicenter Phase 1 Clinical and Pharmacokinetic Study of DCC-2036 in Subjects With Leukemias (Ph+CML With T315I Mutation Only)
Rationale: DCC-2036 is a potent broad spectrum inhibitor of BCR-ABL kinase. Inhibition of BCR-ABL has been validated for effective treatment of chronic myeloid leukemia (CML). The emergence of mutant forms of BCR-ABL which resist inhibition by imatinib, dasatinib, and nilotinib is associated with loss of efficacy in treatment of the disease. DCC-2036 is a potent inhibitor of resistant mutants of BCR-ABL including the T315I mutation, and would therefore be expected to effectively treat patients who fail to respond to other BCR-ABL inhibitors. DCC-2036 also inhibits FLT3-ITD, TIE2, KDR, LYN and TRKA kinases. Purpose: to assess the safety and tolerability in patients after continuous administration of DCC-2036 and to determine recommended doses for the conduct of a Phase 2 efficacy trial.
Read the detailed description
This study will include patients with one of the following: (1) Philadelphia chromosome-positive (Ph+) Chronic myeloid leukemia (CML); (2) FLT3 (gene) internal tandem duplication positive acute myeloid leukemia [FLT3 (gene) ITD-AML]. The investigational drug DCC-2036 has shown in the laboratory to affect different kinds of proteins in CML or AML cancer cells, which may help to stop these cancer cells from growing. This is a Phase 1 study. This Phase 1 study will test the highest safe dose of the investigational drug, DCC-2036, how often the drug should be given, and how well Ph+ CML and AML patients will tolerate DCC-2036. Patients' study doctor will review their past medical history, surgery(s), known allergies, and past/current medications. In addition, blood tests and bone marrow biopsies will be taken to determine if persons are eligible to participate in this study.
During the first part of this study, patients will receive different amounts of DCC-2036 to determine the highest safe dose. Multiple dose levels of DCC-2036 will be tested and as long as no medically unacceptable side effects are noted, the dose will be increased for the next group of study patients. When the highest dose is reached, a larger number of patients will be enrolled to receive DCC-2036 at the highest (safe) dose level. Additional study patients will be enrolled in a group called an "Expansion Group" and receive the study drug at the highest well tolerated dose. Evaluation of the safety and efficacy (how well the study medication treats leukemia) will be studied in this trial. Disease assessment will be monitored as follows: (1) Blood samples will be collected for disease response and for mutational analysis if disease has gotten worse (progressed); (2) Bone marrow samples may be collected by having an area of the hip or chest bone numbed with an anesthetic and a small amount of bone marrow drawn through a needle; (3) For CML patients only, blood samples will be collected for BCR-ABL transcript levels. Patient safety is of primary importance in this Phase 1 study. Safety assessment will be monitored as follows: (1) Physical examinations will be performed regularly during your doctor's visits; (2) Routine blood tests will be performed on a regular basis to assess potential side effects that may be caused by study medication on different organs like (and not limited to) liver, kidney and bone marrow; (3) Based on reports of potential side effects to the heart that may be caused by study medication, patients will be required to have echocardiograms and blood draws to measure the level of serum N-terminal fragment pro B-type natriuretic peptide (NT-proBNP). An echocardiogram is a noninvasive test that uses sound waves to produce images of your heart. These images will tell the doctor how a patient's heart is beating and pumping. The NT-proBNP is a blood test that will help the patient's doctor evaluate how well the heart works. After initial testing is completed, patients will then be required to have these safety evaluations performed at intervals of 3-cycles (approximately every 3 months) for as long as they are taking the study medication. Patients who experience muscle weakness or peripheral neuropathy will be assessed by blood draws to measure creatine phosphokinase (CPK) levels. Measuring CPK levels may help the patient's doctor determine whether or not the symptoms they are experiencing are the result of muscle damage or due to other causes. The most common eye disorders include blurred vision, dry eyes, and visual impairment. Patients will be required to have complete eye (ophthalmologic) evaluations. After initial ophthalmologic exams, patients will be required to have an exam after the completion of every 3 cycles of study medication (approximately every 3 months) and at the time they stop taking study medication. Blood samples will be collected for pharmacokinetic analysis. Pharmacokinetics is the study of the bodily absorption, distribution, metabolism, and excretion of drugs. Blood samples will also be collected for pharmacodynamic analysis. Pharmacodynamic analysis measures biomarkers that are either proteins or genes (also called DNA) that are associated with a disease that may also be related to how you respond to a treatment or what type of side effects may happen. The investigational drug DCC-2036 has not been approved by the United States Food and Drug Administration (FDA). The FDA allows DCC-2036 to be used in research studies only. DCC-2036 will be given to patients only during this study and not after the study is over.
- Conditions
- Chronic Myeloid Leukemia
- Being tested
- DCC-2036
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DCC-2036Drug
Also called rebastinib
150 mg BID tablets, continuous dosing of 28 day cycles
| Study group | Role | What they receive |
|---|---|---|
| DCC-2036 | Experimental | This is a single arm study Receives: Drug: DCC-2036 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess the safety and tolerability of the drug
Measured: Completion of the study
Secondary outcomes (1)
Determine the Pharmacokinetic profile and preliminary evidence of clinical response
Measured: Completion of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2009 (estimated)
- Study startMar 2009
- Primary completionJan 2013
- Study completionJan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chronic Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Deciphera Pharmaceuticals, LLCThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Deciphera Pharmaceuticals, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jorge Cortes, MD, Principal investigator, M.D. Anderson Cancer CenterHedy P Smith, MD, Principal investigator, Tufts Medical CenterMoshe Talpaz, MD, Principal investigator, Univ. of Michigan Comprehensive Cancer CenterKapil Bhalla, MD, Principal investigator, University of KansasRichard A Larson, MD, Principal investigator, University of ChicagoH.Jean Khoury, MD, Principal investigator, Emory UniversityB. Douglas Smith, MD, Principal investigator, Sidney Kimmel Cancer Center at Johns HopkinsEhab Atallah, MD, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00827138
- Sponsor's protocol ID
- Protocol 2036-01
- Status last verified
- Jul 2014
- First submitted
- 21 Jan 2009
- Last updated
- 18 Jul 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Cortes J, Talpaz M, Smith HP, Snyder DS, Khoury J, Bhalla KN, Pinilla-Ibarz J, Larson R, Mitchell D, Wise SC, Rutkoski TJ, Smith BD, Flynn DL, Kantarjian HM, Rosen O, Van Etten RA. Phase 1 dose-finding study of rebastinib (DCC-2036) in patients with relapsed chronic myeloid leukemia and acute myeloid leukemia. Haematologica. 2017 Mar;102(3):519-528. doi: 10.3324/haematol.2016.152710. Epub 2016 Dec 7.
PubMed 27927766O'Hare T, Zabriskie MS, Eiring AM, Deininger MW. Pushing the limits of targeted therapy in chronic myeloid leukaemia. Nat Rev Cancer. 2012 Jul 24;12(8):513-26. doi: 10.1038/nrc3317.
PubMed 22825216
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Phase 1 Clinical and Pharmacokinetic Study of DCC-2036 in Subjects With Leukemias (Ph+CML With T315I Mutation Only)
- ClinicalTrials.gov ID
- NCT00827138
- Acronym / sponsor ID
- Protocol 2036-01
- Conditions
- Chronic Myeloid Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Deciphera Pharmaceuticals, LLCIndustry (pharma, biotech, devices)
- Study start
- Mar 2009
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 22 Jan 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Rationale: DCC-2036 is a potent broad spectrum inhibitor of BCR-ABL kinase. Inhibition of BCR-ABL has been validated for effective treatment of chronic myeloid leukemia (CML). The emergence of mutant forms of BCR-ABL which resist inhibition by imatinib, dasatinib, and nilotinib is associated with loss of efficacy in treatment of the disease. DCC-2036 is a potent inhibitor of resistant mutants of BCR-ABL including the T315I mutation, and would therefore be expected to effectively treat patients who fail to respond to other BCR-ABL inhibitors. DCC-2036 also inhibits FLT3-ITD, TIE2, KDR, LYN and TRKA kinases. Purpose: to assess the safety and tolerability in patients after continuous administration of DCC-2036 and to determine recommended doses for the conduct of a Phase 2 efficacy trial.
Detailed description
This study will include patients with one of the following: (1) Philadelphia chromosome-positive (Ph+) Chronic myeloid leukemia (CML); (2) FLT3 (gene) internal tandem duplication positive acute myeloid leukemia [FLT3 (gene) ITD-AML]. The investigational drug DCC-2036 has shown in the laboratory to affect different kinds of proteins in CML or AML cancer cells, which may help to stop these cancer cells from growing. This is a Phase 1 study. This Phase 1 study will test the highest safe dose of the investigational drug, DCC-2036, how often the drug should be given, and how well Ph+ CML and AML patients will tolerate DCC-2036. Patients' study doctor will review their past medical history, surgery(s), known allergies, and past/current medications. In addition, blood tests and bone marrow biopsies will be taken to determine if persons are eligible to participate in this study.
During the first part of this study, patients will receive different amounts of DCC-2036 to determine the highest safe dose. Multiple dose levels of DCC-2036 will be tested and as long as no medically unacceptable side effects are noted, the dose will be increased for the next group of study patients. When the highest dose is reached, a larger number of patients will be enrolled to receive DCC-2036 at the highest (safe) dose level. Additional study patients will be enrolled in a group called an "Expansion Group" and receive the study drug at the highest well tolerated dose. Evaluation of the safety and efficacy (how well the study medication treats leukemia) will be studied in this trial. Disease assessment will be monitored as follows: (1) Blood samples will be collected for disease response and for mutational analysis if disease has gotten worse (progressed); (2) Bone marrow samples may be collected by having an area of the hip or chest bone numbed with an anesthetic and a small amount of bone marrow drawn through a needle; (3) For CML patients only, blood samples will be collected for BCR-ABL transcript levels. Patient safety is of primary importance in this Phase 1 study. Safety assessment will be monitored as follows: (1) Physical examinations will be performed regularly during your doctor's visits; (2) Routine blood tests will be performed on a regular basis to assess potential side effects that may be caused by study medication on different organs like (and not limited to) liver, kidney and bone marrow; (3) Based on reports of potential side effects to the heart that may be caused by study medication, patients will be required to have echocardiograms and blood draws to measure the level of serum N-terminal fragment pro B-type natriuretic peptide (NT-proBNP). An echocardiogram is a noninvasive test that uses sound waves to produce images of your heart. These images will tell the doctor how a patient's heart is beating and pumping. The NT-proBNP is a blood test that will help the patient's doctor evaluate how well the heart works. After initial testing is completed, patients will then be required to have these safety evaluations performed at intervals of 3-cycles (approximately every 3 months) for as long as they are taking the study medication. Patients who experience muscle weakness or peripheral neuropathy will be assessed by blood draws to measure creatine phosphokinase (CPK) levels. Measuring CPK levels may help the patient's doctor determine whether or not the symptoms they are experiencing are the result of muscle damage or due to other causes. The most common eye disorders include blurred vision, dry eyes, and visual impairment. Patients will be required to have complete eye (ophthalmologic) evaluations. After initial ophthalmologic exams, patients will be required to have an exam after the completion of every 3 cycles of study medication (approximately every 3 months) and at the time they stop taking study medication. Blood samples will be collected for pharmacokinetic analysis. Pharmacokinetics is the study of the bodily absorption, distribution, metabolism, and excretion of drugs. Blood samples will also be collected for pharmacodynamic analysis. Pharmacodynamic analysis measures biomarkers that are either proteins or genes (also called DNA) that are associated with a disease that may also be related to how you respond to a treatment or what type of side effects may happen. The investigational drug DCC-2036 has not been approved by the United States Food and Drug Administration (FDA). The FDA allows DCC-2036 to be used in research studies only. DCC-2036 will be given to patients only during this study and not after the study is over.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DCC-2036 | Experimental | Drug: DCC-2036This is a single arm study |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| DCC-2036Also: rebastinib150 mg BID tablets, continuous dosing of 28 day cycles | Drug | DCC-2036 |
Primary outcome
Assess the safety and tolerability of the drug
Time frame: Completion of the study
1 secondary outcome
Determine the Pharmacokinetic profile and preliminary evidence of clinical response
Time frame: Completion of the study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2014.
- Derived from this study: PubMed 27927766Cortes J, Talpaz M, Smith HP, Snyder DS, Khoury J, Bhalla KN, Pinilla-Ibarz J, Larson R, Mitchell D, Wise SC, Rutkoski TJ, Smith BD, Flynn DL, Kantarjian HM, Rosen O, Van Etten RA. Phase 1 dose-finding study of rebastinib (DCC-2036) in patients with relapsed chronic myeloid leukemia and acute myeloid leukemia. Haematologica. 2017 Mar;102(3):519-528. doi: 10.3324/haematol.2016.152710. Epub 2016 Dec 7.
- Derived from this study: PubMed 22825216O'Hare T, Zabriskie MS, Eiring AM, Deininger MW. Pushing the limits of targeted therapy in chronic myeloid leukaemia. Nat Rev Cancer. 2012 Jul 24;12(8):513-26. doi: 10.1038/nrc3317.
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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.
Jorge Cortes, MD principal investigator
M.D. Anderson Cancer Center
Hedy P Smith, MD principal investigator
Tufts Medical Center
Moshe Talpaz, MD principal investigator
Univ. of Michigan Comprehensive Cancer Center
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DCC-2036 in people with Chronic Myeloid Leukemia, run by Deciphera Pharmaceuticals, LLC at 10 sites 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?
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: finished, as of the sponsor's last update on 18 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Assess the safety and tolerability of the drug (time frame: Completion of the study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00827138, which also lists 2 linked publications.
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 18 Jul 2014.