Chronic Myelogenous LeukemiaPhase 1NCT00660920
Safety Study of AP24534 to Treat Chronic Myelogenous Leukemia (CML) and Other Hematological Malignancies
A Phase 1 study testing Ponatinib in people with Chronic Myelogenous Leukemia and Hematologic Malignancies, run by Ariad Pharmaceuticals at 5 sites in United States.
Trial summary
The purpose of this study is to determine the maximum tolerated dose or a recommended dose of oral AP24534 in a defined schedule in patients with refractory or advanced chronic myelogenous leukemia and other refractory hematologic malignancies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Myelogenous Leukemia, Hematologic Malignancies
- What is being tested?
- Ponatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 81 participants
- Where
- 5 sitesUnited States
- Study dates
- Jun 2008to May 2016
- 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
Who may be able to join
- Male or Female ≥ 18 years old
- Diagnosed hematologic malignancy (other than lymphoma) that has relapsed or is refractory to standard care or for which no standard care is available or acceptable
- Able to give written informed consent
- ECOG performance status ≤ 2
- BSA ≥ 1.5 m² (first cohort only)
- Minimum life expectancy of 3 months or more
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- Adequate renal function defined as serum creatinine <1.5× upper limit of normal (ULN) for institution
- Adequate hepatic function (defined as: Total bilirubin <1.5 × ULN for institution; ALT and AST <2.5 × ULN for institution [<5 X ULN if liver involvement with leukemia]; Prothrombin time <1.5 × ULN)
- Ability to comply with study procedures in the Investigator's opinion
- Adequate cardiac function defined as ejection fraction (EF) >40% by any method of the investigator's choice
- Normal QTcF interval on screening ECG evaluation, defined as QTcF of <450 ms.
- For females of childbearing potential, a negative pregnancy test must be documented prior to enrollment
- Female patients who are of childbearing potential must agree to use an effective form of contraception with their sexual partners throughout participation in this study
Who cannot join
- Have had cytotoxic chemotherapy or radiotherapy within 21 days prior to entering the study, or those who have not recovered from adverse events due to agents administered more than 28 days earlier with the exception of alopecia
- Received any other investigational agents or have received an investigational agent within 14 days of starting ponatinib
- Malabsorption syndrome or other illness which could affect oral absorption
- Significant uncontrolled cardiac disease
- Patients taking medicinal products that are known to be associated with prolongation of the QT interval on the electrocardiogram.
- Uncontrolled hypertension (Diastolic BP >100 mmHg; Systolic >150 mmHg)
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- Uncontrolled intercurrent illness
- Pregnant
- Known infection with HIV
- Autologous or allogeneic stem cell transplant < 3 months prior to enrollment; any evidence of ongoing graft versus host disease (GVHD), or GVHD requiring immunosuppressive therapy
- Another primary malignancy within the past 3 years
- Any condition or illness which, in the opinion of the investigator, would compromise patient safety or interfere with the evaluation of the safety of the drug
- Patients taking medicinal products that are known to be associated with prolongation of the QT interval on the electrocardiogram
- Major surgery (with the exception of intravenous catheter placement or bone marrow biopsy) within 14 days prior to initiating ponatinib therapy
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
ARIAD Investigational Site #011
Ann Arbor, Michigan, 48109
ARIAD Investigational Site #005
Houston, Texas, 70030
ARIAD Investigational Site #076
Nashville, Tennessee, 37203
ARIAD Investigational Site #048
Portland, Oregon, 97239
ARIAD Investigational Site #075
San Francisco, California, 94143
About this study
Official title: A Phase 1 Dose Escalation Trial to Determine the Safety, Tolerability and Maximum Tolerated Dose of Oral AP24534 in Patients With Refractory or Advanced Chronic Myelogenous Leukemia and Other Hematologic Malignancies
The purpose of this study is to determine the maximum tolerated dose or a recommended dose of oral AP24534 in a defined schedule in patients with refractory or advanced chronic myelogenous leukemia and other refractory hematologic malignancies.
- Being tested
- Ponatinib
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PonatinibDrug
Also called AP24534, Iclusig
Comparison of different dosages of drug given orally once per day.
| Study group | Role | What they receive |
|---|---|---|
| ponatnib | Experimental | Comparison of different dosages of ponatinib given orally once per day. Receives: Drug: Ponatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine Maximum Tolerated Dose (MTD) or Recommended dose
Determine MTD dose or a recommended dose of oral ponatinib in a defined schedule (QD) in patients with refractory or advanced chronic myelogenous leukemia and other refractory hematologic malignancies.
Measured: Up to
Secondary outcomes (5)
To examine the safety of AP24534 in patients with resistant/refractory hematologic malignancies
Measured: Up to 7 years
To describe the anti-tumor activity of AP24534 in patients with refractory hematologic malignancies
Measured: Up to 7 years
To examine the pharmacokinetics of AP24534
Measured: Up to 2 cycles (1 cycle = 28 days)
To examine pharmacodynamic activity of AP24534 in CML and Ph + ALL patients
Measured: Up to 7 years
To describe potential pharmacogenomic markers of AP24534 anti-tumor activity
Measured: Up to 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2008 (estimated)
- Study startJun 2008
- Primary completionMay 2016
- Study completionMay 2016
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 Myelogenous LeukemiaStudies of the same condition, open and under way.
- 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
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ariad Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00660920
- Sponsor's protocol ID
- AP24534-07-101
- Status last verified
- Feb 2018
- First submitted
- 15 Apr 2008
- Last updated
- 16 May 2018
- Results posted
- No
- Data monitoring committee
- No
- Expanded access
- Available
Publications
Hanley MJ, Diderichsen PM, Narasimhan N, Srivastava S, Gupta N, Venkatakrishnan K. Population Pharmacokinetics of Ponatinib in Healthy Adult Volunteers and Patients With Hematologic Malignancies and Model-Informed Dose Selection for Pediatric Development. J Clin Pharmacol. 2022 Apr;62(4):555-567. doi: 10.1002/jcph.1990. Epub 2021 Dec 16.
PubMed 34699069Cortes JE, Kantarjian H, Shah NP, Bixby D, Mauro MJ, Flinn I, O'Hare T, Hu S, Narasimhan NI, Rivera VM, Clackson T, Turner CD, Haluska FG, Druker BJ, Deininger MW, Talpaz M. Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med. 2012 Nov 29;367(22):2075-88. doi: 10.1056/NEJMoa1205127.
PubMed 23190221
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Dose Escalation Trial to Determine the Safety, Tolerability and Maximum Tolerated Dose of Oral AP24534 in Patients With Refractory or Advanced Chronic Myelogenous Leukemia and Other Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT00660920
- Acronym / sponsor ID
- AP24534-07-101
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Ariad PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jun 2008 (actual)
- Primary completion
- May 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 17 Apr 2008 (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.
The purpose of this study is to determine the maximum tolerated dose or a recommended dose of oral AP24534 in a defined schedule in patients with refractory or advanced chronic myelogenous leukemia and other refractory hematologic malignancies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ponatnib | Experimental | Drug: PonatinibComparison of different dosages of ponatinib given orally once per day. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Male or Female ≥ 18 years old
- Diagnosed hematologic malignancy (other than lymphoma) that has relapsed or is refractory to standard care or for which no standard care is available or acceptable
- Able to give written informed consent
- ECOG performance status ≤ 2
- BSA ≥ 1.5 m² (first cohort only)
Key exclusion criteria (14 listed)
- Have had cytotoxic chemotherapy or radiotherapy within 21 days prior to entering the study, or those who have not recovered from adverse events due to agents administered more than 28 days earlier with the exception of alopecia
- Received any other investigational agents or have received an investigational agent within 14 days of starting ponatinib
- Malabsorption syndrome or other illness which could affect oral absorption
- Significant uncontrolled cardiac disease
- Patients taking medicinal products that are known to be associated with prolongation of the QT interval on the electrocardiogram.
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 |
|---|---|---|
| PonatinibAlso: AP24534, IclusigComparison of different dosages of drug given orally once per day. | Drug | ponatnib |
Primary outcome
Determine Maximum Tolerated Dose (MTD) or Recommended dose
Time frame: Up to
Determine MTD dose or a recommended dose of oral ponatinib in a defined schedule (QD) in patients with refractory or advanced chronic myelogenous leukemia and other refractory hematologic malignancies.
5 secondary outcomes
To examine the safety of AP24534 in patients with resistant/refractory hematologic malignancies
Time frame: Up to 7 years
To describe the anti-tumor activity of AP24534 in patients with refractory hematologic malignancies
Time frame: Up to 7 years
To examine the pharmacokinetics of AP24534
Time frame: Up to 2 cycles (1 cycle = 28 days)
To examine pharmacodynamic activity of AP24534 in CML and Ph + ALL patients
Time frame: Up to 7 years
To describe potential pharmacogenomic markers of AP24534 anti-tumor activity
Time frame: Up to 7 years
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 16 May 2018.
- Derived from this study: PubMed 34699069Hanley MJ, Diderichsen PM, Narasimhan N, Srivastava S, Gupta N, Venkatakrishnan K. Population Pharmacokinetics of Ponatinib in Healthy Adult Volunteers and Patients With Hematologic Malignancies and Model-Informed Dose Selection for Pediatric Development. J Clin Pharmacol. 2022 Apr;62(4):555-567. doi: 10.1002/jcph.1990. Epub 2021 Dec 16.
- Derived from this study: PubMed 23190221Cortes JE, Kantarjian H, Shah NP, Bixby D, Mauro MJ, Flinn I, O'Hare T, Hu S, Narasimhan NI, Rivera VM, Clackson T, Turner CD, Haluska FG, Druker BJ, Deininger MW, Talpaz M. Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med. 2012 Nov 29;367(22):2075-88. doi: 10.1056/NEJMoa1205127.
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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.
The record lists no contact. Use the official record to reach the sponsor.
5 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 Ponatinib in people with Chronic Myelogenous Leukemia and Hematologic Malignancies, run by Ariad Pharmaceuticals at 5 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?
The sponsor lists 13 inclusion and 14 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: finished, as of the sponsor's last update on 16 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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?
Determine Maximum Tolerated Dose (MTD) or Recommended dose (time frame: Up to). 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 NCT00660920, 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 16 May 2018.