Adult Acute Myeloid Leukemia in RemissionPhase 2NCT01841333
PF-04449913 For Patients With Acute Myeloid Leukemia at High Risk of Relapse After Donor Stem Cell Transplant
A Phase 2 study testing PF-04449913 in people with Adult Acute Myeloid Leukemia in Remission and Recurrent Adult Acute Myeloid Leukemia, run by University of Colorado, Denver at 2 sites in United States.
Trial summary
This phase II trial will test whether the Hedgehog signaling pathway inhibitor PF-04449913 can decrease disease relapse in high-risk patients with acute myeloid leukemia after donor stem cell transplant. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Acute Myeloid Leukemia in Remission, Recurrent Adult Acute Myeloid Leukemia
- What is being tested?
- PF-04449913
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 2 sitesUnited States
- Study dates
- 29 Apr 2013to 4 Feb 2020
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- WHO-confirmed AML
- Age ≥18 years
- Between days 28 and 50 post transplantation at the time of initiation of the study drug
- ECOG performance status ≤ 2 (See Appendix A: ECOG Performance Status Scale)
- Life expectancy > 2 months
- Recipient of a myeloablative or non-myeloablative allogeneic HSCT
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- Conditioning regimen to be prescribed at investigator's discretion, but will be prospectively defined as myeloablative or non-myeloablative
- Stable engraftment, as defined by absolute neutrophil count (ANC) ≥ 1000/mm3 and platelets ≥ 25,000/mm3
- In morphologic remission (< 5% marrow blasts) based on BM biopsy performed +/- 5 days of day 28 post- transplantation
- Without clinical signs of active central nervous system disease
- For non-myeloablative transplants, ≥50% CD3 donor chimerism at screening
- High risk of relapse after HSCT, defined as the presence of minimal residual disease as measured by flow cytometry in the absence of evidence of morphologic disease on a bone marrow biopsy prior to HSCT
- Adequate organ function as indicated by the following laboratory values:
- Aspartate aminotransferase (AST), alanine aminotransferase, (ALT) ≤ 3.0 x institutional upper limit of normal (ULN)
- Total bilirubin ≤ 2.0 x institutional ULN, unless documented Gilbert's syndrome
- Either creatinine <1.5 x institutional upper limit of normal (ULN) or creatinine clearance >60 mL/min as calculated by institution's standard formula
- Serum/urine pregnancy test (for females of childbearing potential) that is negative within 72 hours prior to initiation of first dose of treatment (a patient is of childbearing potential if, in the opinion of the investigator, she is biologically capable of having children and is sexually active)
- Female patients of childbearing potential and sexually active males and female partners of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 90 days after the last dose of assigned treatment.
- Subject is able to comply with study procedures and follow-up examinations.
Who cannot join
- Concomitant treatment with other anti-neoplastic agents, with the exception, when clinically indicated, of prophylaxis in the post-transplantation setting with intrathecal chemotherapy
- Use of any other experimental drug or therapy within 28 days of baseline
- Inability to swallow or absorb drug
- Active uncontrolled acute fungal, bacterial, or other infection that is unresponsive to therapy at time of study drug dosing
- Unstable angina pectoris
- New York Heart Association Class III or IV heart failure
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- QTc interval (using Fridericia's correction formula, QTcF, if prolonged) >470 msec
- Active cardiac arrhythmias with rapid ventricular response (defined as heart rate greater than 100 beats/minute)
- Known HIV infection
- Grade III/IV acute GVHD
- Current use or anticipated need for food or drugs that are known moderate/strong CYP3A4 inducers (See Table 1 and section 5.9.2: Prohibited Concomitant Therapy), with the exception of azole antifungals, which are permitted.
- Any medical, psychiatric, addictive or other kind of disorder which compromises the ability of the subject to give written informed consent and/or to comply with procedures.
- Pregnant or lactating females
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Colorado Cancer Center
Aurora, Colorado, 80045
Ohio State University
Columbus, Ohio, 43210
About this study
Official title: A Phase 2 Study of PF-04449913 for the Treatment of Acute Myeloid Leukemia Patients With High Risk of Post-Allogeneic Stem Cell Transplantation Relapse
This phase II trial will test whether the Hedgehog signaling pathway inhibitor PF-04449913 can decrease disease relapse in high-risk patients with acute myeloid leukemia after donor stem cell transplant.
Read the detailed description
Disease relapse is the most common cause of death after allogeneic stem cell transplantation for acute myeloid leukemia. Patients at high risk for relapse may benefit from a novel, biologically rational therapeutic intervention to prevent this outcome. PF-04449913 is a small molecule inhibitor of the hedgehog (Hh) pathway that inhibits the protein Smoothened (SMO). Aberrant Hh signaling may contribute to the survival and expansion of the leukemia stem cell, and inhibiting the Hh pathway can eliminate these cells. Therefore, targeting Hh may be a logical intervention in the post-transplantation setting for those with high risk of relapse. The investigators propose a phase 2 study of PF-04449913 in patients with acute myeloid leukemia who have received an allogeneic stem cell transplantation and are at high risk of relapse.
This is an open label, phase 2 study employing PF-04449913 in acute myeloid leukemia patients who received an allogeneic stem cell transplantation and are at high risk of relapse. Patients will receive consecutive 28-day cycles of PF-04449913 at 100 mg/day, beginning on post-transplantation day 80 +/- 10 days, after their routine post-transplant bone marrow biopsy. Treatment will continue for up to one year or until they experience toxicity or disease relapse. 50 patients will be required for a 90% power to detect a 20% difference in one-year relapse-free survival.
- Being tested
- PF-04449913
- Keywords
- Myeloid leukemia in remission, Recurrent myeloid leukemia
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia, Myeloid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF-04449913Drug
Also called Hedgehog inhibitor
100mg given orally
| Study group | Role | What they receive |
|---|---|---|
| PF-04449913 | Experimental | Beginning 80 days after allogeneic stem cell transplant, patients receive PF-04449913 (100mg) orally once daily on days 1-28. Treatment repeats every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Receives: Drug: PF-04449913 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relapse-free Survival in Days
Days after transplant until disease relapse or death as measured by Kaplan-Meier statistical method.
Measured: 1 year
Secondary outcomes (3)
Remission Duration
Length of time before remission measured in days
Measured: Up to 5 years
Number of Patients With Adverse Events (AE) Related to Glasdegib
Subjects will be evaluated for AEs at each visit with the NCI-CTCAE version 4.03 used as a guide for the grading of severity.
Measured: 30 days
Overall Survival of All Patients
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2013 (estimated)
- Study start29 Apr 2013
- Primary completion8 May 2019
- Study completion4 Feb 2020
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 Adult Acute Myeloid Leukemia in RemissionStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe 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
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- The Leukemia and Lymphoma Society
- Responsible party
- Sponsor
- Investigators
- Daniel A Pollyea, MD, MS, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01841333
- Sponsor's protocol ID
- 12-1558.cc
- Other IDs
- NCI-2013-00824
- Status last verified
- Dec 2021
- First submitted
- 23 Apr 2013
- Last updated
- 25 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of PF-04449913 for the Treatment of Acute Myeloid Leukemia Patients With High Risk of Post-Allogeneic Stem Cell Transplantation Relapse
- ClinicalTrials.gov ID
- NCT01841333
- Acronym / sponsor ID
- 12-1558.cc
- Keywords
- Myeloid leukemia in remission, Recurrent myeloid leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- The Leukemia and Lymphoma Society
- Study start
- 29 Apr 2013 (actual)
- Primary completion
- 8 May 2019 (actual)
- Study completion
- 4 Feb 2020 (actual)
- First posted
- 26 Apr 2013 (estimated)
- Results
- Posted 25 Jan 2022
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 will test whether the Hedgehog signaling pathway inhibitor PF-04449913 can decrease disease relapse in high-risk patients with acute myeloid leukemia after donor stem cell transplant.
Detailed description
Disease relapse is the most common cause of death after allogeneic stem cell transplantation for acute myeloid leukemia. Patients at high risk for relapse may benefit from a novel, biologically rational therapeutic intervention to prevent this outcome. PF-04449913 is a small molecule inhibitor of the hedgehog (Hh) pathway that inhibits the protein Smoothened (SMO). Aberrant Hh signaling may contribute to the survival and expansion of the leukemia stem cell, and inhibiting the Hh pathway can eliminate these cells. Therefore, targeting Hh may be a logical intervention in the post-transplantation setting for those with high risk of relapse. The investigators propose a phase 2 study of PF-04449913 in patients with acute myeloid leukemia who have received an allogeneic stem cell transplantation and are at high risk of relapse.
This is an open label, phase 2 study employing PF-04449913 in acute myeloid leukemia patients who received an allogeneic stem cell transplantation and are at high risk of relapse. Patients will receive consecutive 28-day cycles of PF-04449913 at 100 mg/day, beginning on post-transplantation day 80 +/- 10 days, after their routine post-transplant bone marrow biopsy. Treatment will continue for up to one year or until they experience toxicity or disease relapse. 50 patients will be required for a 90% power to detect a 20% difference in one-year relapse-free survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PF-04449913 | Experimental | Drug: PF-04449913Beginning 80 days after allogeneic stem cell transplant, patients receive PF-04449913 (100mg) orally once daily on days 1-28. Treatment repeats every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- WHO-confirmed AML
- Age ≥18 years
- Between days 28 and 50 post transplantation at the time of initiation of the study drug
- ECOG performance status ≤ 2 (See Appendix A: ECOG Performance Status Scale)
- Life expectancy > 2 months
Key exclusion criteria (13 listed)
- Concomitant treatment with other anti-neoplastic agents, with the exception, when clinically indicated, of prophylaxis in the post-transplantation setting with intrathecal chemotherapy
- Use of any other experimental drug or therapy within 28 days of baseline
- Inability to swallow or absorb drug
- Active uncontrolled acute fungal, bacterial, or other infection that is unresponsive to therapy at time of study drug dosing
- Unstable angina pectoris
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 |
|---|---|---|
| PF-04449913Also: Hedgehog inhibitor100mg given orally | Drug | PF-04449913 |
Primary outcome
Relapse-free Survival in Days
Time frame: 1 year
Days after transplant until disease relapse or death as measured by Kaplan-Meier statistical method.
3 secondary outcomes
Remission Duration
Time frame: Up to 5 years
Number of Patients With Adverse Events (AE) Related to Glasdegib
Time frame: 30 days
Overall Survival of All Patients
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Daniel A Pollyea, MD, MS principal investigator
University of Colorado, Denver
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PF-04449913 in people with Adult Acute Myeloid Leukemia in Remission and Recurrent Adult Acute Myeloid Leukemia, run by University of Colorado, Denver at 2 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 19 inclusion and 13 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 25 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 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 25 Jan 2022). 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?
Relapse-free Survival in Days (time frame: 1 year). 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 25 Jan 2022.