Acute Myelogenous LeukemiaPhase 1NCT01397799
Evaluation of KX2-391 in Elderly Subjects With Acute Myeloid Leukemia (AML)
A Phase 1 study testing KX2-391 in people with Acute Myelogenous Leukemia, run by Kinex Pharmaceuticals Inc. at 3 sites in United States.
Trial summary
This Phase 1b study will determine the maximum tolerated dose of KX2-391 given as a once-daily dose, in elderly patients with acute myelogenous leukemia. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Acute Myelogenous Leukemia
- What is being tested?
- KX2-391
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 3 sitesUnited States
- Study dates
- Dec 2013to Jul 2014
- 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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent.
- Either de novo or secondary AML by 2008 World Health Organization (WHO) classification.
- A bone marrow biopsy and aspirate sample must be obtained between Day -14 to Day -1, and this sample must be confirmed to be adequate for morphologic analysis of marrow cellularity and blast percentage before the first dose of KX2-391 is administered.
- A bone aspirate sample (with or without biopsy) must be obtained after the patient signs the informed consent document and be submitted for baseline pharmacodynamic assessment. Although this will usually be obtained as part of the baseline assessment marrow biopsy and aspirate procedure described above, if a complete marrow evaluation was performed prior to the patient signing informed consent, a dedicated bone marrow aspiration for this sample can be performed after the patient signs informed consent, so long as the pre-consent biopsy and aspirate procedure were done within 14 days of the first dose of KX2-391.
- Adults age ≥ 60 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
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- Life expectancy of at least 6 weeks from first day of study drug administration
- Adequate liver function (AST/ALT < 3 x upper limit of normal (ULN), Alk Phos < 2.5 x ULN, and Direct Bilirubin < 1.5 x ULN)
- Adequate renal function (serum creatinine < 1.5 x ULN)
- Documented QTc ≤ 0.48 seconds within 14 days of first dose of KX2-391
Who cannot join
- Subjects with acute promyelocytic leukemia (APL, AML FAB type M3), or chronic myelogenous leukemia (CML).
- Have not resolved toxicity from previous anticancer treatments or investigational agents, other than hematologic toxicities or alopecia, to ≤ Grade 1 according to the most recent CTCAE guidelines.
- Subjects with rapidly proliferative AML that is likely to require treatment within the next 30 days (e.g. hydroxyurea).
- Received an investigational agent within 5 half-lives of that agent from the anticipated Cycle 1 Day 1 of treatment with KX2-391.
- Have clinical evidence of central nervous system involvement by AML or other malignancy.
- History of major surgery to the upper gastrointestinal tract, or have a history of inflammatory bowel disease, malabsorption syndrome, or other medical condition that may interfere with oral drug absorption.
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- Uncontrolled hypertension (at time of dosing).
- Other medical conditions which, in the opinion of the investigator, make it undesirable for the subject to participate in the study.
- Known history of hepatitis B, C, or human immunodeficiency (HIV) infection.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection. Patients receiving intravenous antibiotics for infections that are under control may be included in this study.
- Subjects who are unwilling or unable to comply with the protocol.
- Subjects who are taking moderate or strong CYP450 3A4 modulators, with the exception of fluconazole (see Appendix 2 for list of medications currently known to be moderate or strong CYP450 3A4 modulators). Subjects who can safely discontinue these medications can become eligible for this trial.
- Subjects receiving azole-based antifungal prophylaxis other than fluconazole (see Appendix 2) who are unable to switch their prophylaxis to fluconazole, or discontinue antifungal prophylaxis, for 7 days prior to first day of study drug administration.
- Active cancer, other than AML, requiring systemic chemotherapy or biological therapy within 6 months of study entry. Patients who have received only hormonal therapy in the neoadjuvant or adjuvant setting in the past 6 months may participate in this study.
- Symptomatic congestive heart failure, unstable angina, or cardiac arrhythmia.
- Other conditions that could jeopardize the subject's ability to comply with the protocol, including, but not limited to, dementia, psychosis, or other major psychiatric disorder
- Pregnant or breast feeding
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Roswell Park Cancer Institute
Buffalo, New York, 14263
Weill Cornell Medical College
New York, New York, 10065
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
About this study
Official title: A Phase 1b Rising Multiple-Dose Study to Evaluate Safety, Tolerability and Activity of KX2-391 in Elderly Subjects With Acute Myeloid Leukemia Who Are Refractory to or Have Declined Standard Induction Therapy
This Phase 1b study will determine the maximum tolerated dose of KX2-391 given as a once-daily dose, in elderly patients with acute myelogenous leukemia.
Read the detailed description
KX2-391 has been evaluated in a Phase 1 dose escalation study in patients with solid tumors using twice-daily dosing. This study will employ the Storer's two-stage design to determine the maximum tolerated dose of KX2-391 mono-therapy,given as a once-daily oral dose,in elderly patients with acute myelogenous leukemia (AML) who are refractory to or have declined standard induction therapy. The safety, tolerability, pharmacokinetics and activity of KX2-391 will be evaluated.
- Conditions
- Acute Myelogenous Leukemia
- Being tested
- KX2-391
- Keywords
- Acute Myelogenous Leukemia, AML, Refractory, Elderly
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KX2-391Drug
Also called KX01
Oral dose solution, once-daily dosing for 28-days. Subjects may continue beyond the first 28-days until disease progression or unacceptable toxicity develops.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Subjects will be enrolled into a 28-day dose-escalation study. If no DLT's are observed during the first 28 days, subjects are eligible to continue treatment in the Extension Phase and can remain on treatment until toxicity occurs or until disease progression. Receives: Drug: KX2-391 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the maximum tolerated dose of KX2-391 when given once-daily to AML patients.
The MTD will be used to determine the recommended Phase 2 dose that is associated with an approximately 33% DLT rate during the first 28 days of treatment in elderly patients with AML
Measured: 28 days
Secondary outcomes (1)
Evaluate pharmacokinetics, pharmacodynamics and activity of KX2-391.
The pharmacokinetics and pharmacodynamics of KX2-391 will be evaluated in AML patients by measuring serum and bone marrow levels of drug and evaluating the disruption of microtubule networks in these samples to determine whether target inhibition has occurred at the doses tested. Hematological and bone marrow response will be assessed according to International Working Group (IWG)-AML criteria.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2011 (estimated)
- Study startDec 2013
- Primary completionJul 2014
- Study completionJul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute 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
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kinex Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- James Thompson, MD, Principal investigator, Roswell Park Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01397799
- Sponsor's protocol ID
- KX01-03-11
- Status last verified
- Dec 2015
- First submitted
- 18 Jul 2011
- Last updated
- 7 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Kasner MT, Halloran MB, Pan J, Ritchie EK, Fetterly GJ, Kramer D, Hangauer DG, Thompson JE. A phase Ib dose escalation study of oral monotherapy with KX2-391 in elderly patients with acute myeloid leukemia. Invest New Drugs. 2022 Aug;40(4):773-781. doi: 10.1007/s10637-022-01255-1. Epub 2022 May 17.
PubMed 35579731
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Rising Multiple-Dose Study to Evaluate Safety, Tolerability and Activity of KX2-391 in Elderly Subjects With Acute Myeloid Leukemia Who Are Refractory to or Have Declined Standard Induction Therapy
- ClinicalTrials.gov ID
- NCT01397799
- Acronym / sponsor ID
- KX01-03-11
- Conditions
- Acute Myelogenous Leukemia
- Keywords
- Acute Myelogenous Leukemia, AML, Refractory, Elderly
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Kinex Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Study start
- Dec 2013
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 20 Jul 2011 (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.
This Phase 1b study will determine the maximum tolerated dose of KX2-391 given as a once-daily dose, in elderly patients with acute myelogenous leukemia.
Detailed description
KX2-391 has been evaluated in a Phase 1 dose escalation study in patients with solid tumors using twice-daily dosing. This study will employ the Storer's two-stage design to determine the maximum tolerated dose of KX2-391 mono-therapy,given as a once-daily oral dose,in elderly patients with acute myelogenous leukemia (AML) who are refractory to or have declined standard induction therapy. The safety, tolerability, pharmacokinetics and activity of KX2-391 will be evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: KX2-391Subjects will be enrolled into a 28-day dose-escalation study. If no DLT's are observed during the first 28 days, subjects are eligible to continue treatment in the Extension Phase and can remain on treatment until toxicity occurs or until disease progression. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Written informed consent.
- Either de novo or secondary AML by 2008 World Health Organization (WHO) classification.
- A bone marrow biopsy and aspirate sample must be obtained between Day -14 to Day -1, and this sample must be confirmed to be adequate for morphologic analysis of marrow cellularity and blast percentage before the first dose of KX2-391 is administered.
- A bone aspirate sample (with or without biopsy) must be obtained after the patient signs the informed consent document and be submitted for baseline pharmacodynamic assessment. Although this will usually be obtained as part of the baseline assessment marrow biopsy and aspirate procedure described above, if a complete marrow evaluation was performed prior to the patient signing informed consent, a dedicated bone marrow aspiration for this sample can be performed after the patient signs informed consent, so long as the pre-consent biopsy and aspirate procedure were done within 14 days of the first dose of KX2-391.
- Adults age ≥ 60 years of age
Key exclusion criteria (17 listed)
- Subjects with acute promyelocytic leukemia (APL, AML FAB type M3), or chronic myelogenous leukemia (CML).
- Have not resolved toxicity from previous anticancer treatments or investigational agents, other than hematologic toxicities or alopecia, to ≤ Grade 1 according to the most recent CTCAE guidelines.
- Subjects with rapidly proliferative AML that is likely to require treatment within the next 30 days (e.g. hydroxyurea).
- Received an investigational agent within 5 half-lives of that agent from the anticipated Cycle 1 Day 1 of treatment with KX2-391.
- Have clinical evidence of central nervous system involvement by AML or other malignancy.
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 |
|---|---|---|
| KX2-391Also: KX01Oral dose solution, once-daily dosing for 28-days. Subjects may continue beyond the first 28-days until disease progression or unacceptable toxicity develops. | Drug | Treatment |
Primary outcome
To determine the maximum tolerated dose of KX2-391 when given once-daily to AML patients.
Time frame: 28 days
The MTD will be used to determine the recommended Phase 2 dose that is associated with an approximately 33% DLT rate during the first 28 days of treatment in elderly patients with AML
1 secondary outcome
Evaluate pharmacokinetics, pharmacodynamics and activity of KX2-391.
Time frame: 28 days
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 7 Dec 2015.
- Derived from this study: PubMed 35579731Kasner MT, Halloran MB, Pan J, Ritchie EK, Fetterly GJ, Kramer D, Hangauer DG, Thompson JE. A phase Ib dose escalation study of oral monotherapy with KX2-391 in elderly patients with acute myeloid leukemia. Invest New Drugs. 2022 Aug;40(4):773-781. doi: 10.1007/s10637-022-01255-1. Epub 2022 May 17.
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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.
James Thompson, MD principal investigator
Roswell Park Cancer Institute
3 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 KX2-391 in people with Acute Myelogenous Leukemia, run by Kinex Pharmaceuticals Inc. at 3 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 10 inclusion and 17 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 7 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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?
To determine the maximum tolerated dose of KX2-391 when given once-daily to AML patients. (time frame: 28 days). 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 NCT01397799, which also lists 1 linked publication.
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 7 Dec 2015.