Acute Myeloid Leukemia With Gene MutationsPhase 2NCT02723435
Midostaurin in Treating Older Patients With Mutated Acute Myeloid Leukemia Post-Transplant
A Phase 2 study testing Midostaurin in people with Acute Myeloid Leukemia With Gene Mutations and Adult Acute Myeloid Leukemia in Remission, run by Stanford University.
Trial summary
This phase 2 trial studies the side effects and how well midostaurin works in treating older patients with acute myeloid leukemia with change in genetic material post-hematopoietic cell transplantation. Midostaruin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Acute Myeloid Leukemia With Gene Mutations, Adult Acute Myeloid Leukemia in Remission
- What is being tested?
- Midostaurin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Start not givento Apr 2018
- Phase
- Phase 2
- 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
- Elderly patients with FLT3-mutated acute myeloid leukemia (AML)
- Prior enrollment in Stanford study IRB-25737
- In continued complete remission
- ≥ 30 days but ≤ 90 days post allogeneic hematopoietic cell transplant (HCT); treatment on this study protocol must begin before day 90 post-HCT
- Absolute neutrophil count (ANC) ≥ 1000 cells/uL
- Hemoglobin ≥ 8.0 g/dL and not requiring regular transfusions
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- Platelets ≥ 50,000 cells/uL and not requiring regular transfusions
- Aspartate aminotransferase (AST) ≤ 2.5 times upper limit of normal (ULN)
- Alanine aminotransferase (ALT) ≤ 2.5 X ULN
- Serum bilirubin ≤ 2.5 times ULN
- Ability to give written informed consent, including via legally authorized representative
- Corrected QT (QTc) ≤ 450 msec
- Ejection fraction (EF) ≥ 45% by 2-dimensional transthoracic echocardiography (TTE) or multiple-gated acquisition (MUGA)
- Sexually active males, including vasectomized males, must agree via informed consent to use a condom during vaginal, anal, or oral intercourse, while taking midostaurin and for 5 months after stopping midostaurin
- Females must have or be:
- Negative pregnancy test, within 21 days of the first dose of midostaurin OR
- Not of childbearing potential as follows:
- Has undergone a hysterectomy or bilateral oophorectomy;
- Has not had menses at any time in the preceding 24 consecutive months
Who cannot join
- Uncontrolled acute graft-vs-host disease (GVHD) grade 3 to 4
- Uncontrolled active infection
- Evidence of active AML (eg, circulating peripheral blasts on complete blood count)
- Known confirmed diagnosis of human immunodeficiency virus (HIV) infection
- Known confirmed diagnosis of active viral hepatitis
- QTc > 450 msec
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- Congenital long QT syndrome
- History of presence of sustained ventricular tachycardia, history of ventricular fibrillation or torsades de pointes
- Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm)
- Bifascicular block (right bundle branch block plus left anterior hemiblock)
- Congestive heart failure (CHF) New York Heart Association (NYHA) class 3 or 4
- Cardiac ejection fraction (EF) < 45% within 28 days prior to starting cycle 1
- Other known malignancy (except carcinoma in situ)
- Other concurrent severe and/or uncontrolled medical condition which could compromise participation in the study, eg:
- Uncontrolled diabetes
- Chronic active pancreatitis
- Myocardial infarction within 6 months
- Poorly-controlled hypertension
- Chronic kidney disease
- Received any investigational agent within 30 days prior to day 1
- Antineoplastic chemotherapy or radiotherapy within 28 days prior to cycle 1
- No plans for concurrent chemotherapy while on study (exception: antineoplastic drugs used as part of GVHD prophylaxis or treatment)
- Any surgical procedure, excluding central venous catheter placement, bone marrow biopsy or other minor procedures (eg, skin biopsy) within 14 days of day 1
- Unwillingness or inability to comply with the protocol
- Known malignant disease of the central nervous system
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to midostaurin
- Concomitant use of strong inhibitors of cytochrome P450 family 3 subfamily A member 4 (CYP3A4)
- Pregnant or lactating
- Women of child-bearing potential
About this study
Official title: An Open-Label Extension Study of Post-Transplant Maintenance Midostaurin (PKC412) in Elderly Patients (Age ≥ 60 Years) With FLT3-ITD/TKD Mutated AML Who Previously Received Midostaurin and Decitabine as Part of Study HEMAML0022 / CPKC412AUS27T
This phase 2 trial studies the side effects and how well midostaurin works in treating older patients with acute myeloid leukemia with change in genetic material post-hematopoietic cell transplantation. Midostaruin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving midostaruin post-transplant may improve patient outcomes.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the efficacy and safety of maintenance midostaurin (a fms related tyrosine kinase 3 [FLT3] inhibitor) for elderly patients with FLT3-internal tandem duplication (ITD)/tyrosine kinase domain (TKD) mutated acute myeloid leukemia (AML) who were previously enrolled on study HEMAML0022/CPKC412AUS27T and have then undergone allogeneic transplant.
SECONDARY OBJECTIVES:
- To determine whether maintenance midostaurin after allogeneic transplant decreases the relapse rate in patients with FLT3-ITD/TKD mutated AML.
OUTLINE:
Beginning 30 days post-hematopoietic cell transplantation (HCT), patients receive midostaurin orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then up to 1 year.
- Being tested
- Midostaurin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MidostaurinDrug
Also called Rydapt, CGP 41251, N-benzoyl-staurosporine, PKC-412
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Midostaurin | Experimental | Beginning 30 days post-HCT, participants receive oral midostaurin twice-a-day in 28-day treatment cycles, continuing up to 12 cycles in the absence of disease progression or unacceptable toxicity. Receives: Drug: Midostaurin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free survival
Measured: Up to 1 year
Incidence of adverse events using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Measured: Up to 30 days
Overall survival
Calculated and reported with Kaplan Meier curves. The statistical analyses will focus on estimation rather than hypothesis testing. Two-sided 95% confidence intervals will be presented, using the Clopper-Pearson method for proportions and using Greenwood's formula for time to event outcomes.
Measured: Up to 1 year
Relapse free survival
Calculated and reported with Kaplan Meier curves. The statistical analyses will focus on estimation rather than hypothesis testing. Two-sided 95% confidence intervals will be presented, using the Clopper-Pearson method for proportions and using Greenwood's formula for time to event outcomes.
Measured: Up to 1 year
Secondary outcomes (1)
Relapse rate after allogeneic transplant
Described using proportions.
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2016 (estimated)
- Primary completionApr 2018
- Study completionApr 2018
Why it stopped: Logistical and administrative issues
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid Leukemia With Gene MutationsStudies of the same condition, open and under way.
- More trials run by Stanford 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Iberri, Stanford University
- Investigators
- David Iberri, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02723435
- Sponsor's protocol ID
- IRB-31582
- Other IDs
- NCI-2016-00424, HEMAML0022-EXT, NCT02723435
- Status last verified
- May 2018
- First submitted
- 25 Mar 2016
- Last updated
- 4 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Extension Study of Post-Transplant Maintenance Midostaurin (PKC412) in Elderly Patients (Age ≥ 60 Years) With FLT3-ITD/TKD Mutated AML Who Previously Received Midostaurin and Decitabine as Part of Study HEMAML0022 / CPKC412AUS27T
- ClinicalTrials.gov ID
- NCT02723435
- Acronym / sponsor ID
- IRB-31582
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Logistical and administrative issues
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Primary completion
- Apr 2018 (actual)
- Study completion
- Apr 2018 (actual)
- First posted
- 30 Mar 2016 (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 2 trial studies the side effects and how well midostaurin works in treating older patients with acute myeloid leukemia with change in genetic material post-hematopoietic cell transplantation. Midostaruin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving midostaruin post-transplant may improve patient outcomes.
Detailed description
PRIMARY OBJECTIVES:
- To determine the efficacy and safety of maintenance midostaurin (a fms related tyrosine kinase 3 [FLT3] inhibitor) for elderly patients with FLT3-internal tandem duplication (ITD)/tyrosine kinase domain (TKD) mutated acute myeloid leukemia (AML) who were previously enrolled on study HEMAML0022/CPKC412AUS27T and have then undergone allogeneic transplant.
SECONDARY OBJECTIVES:
- To determine whether maintenance midostaurin after allogeneic transplant decreases the relapse rate in patients with FLT3-ITD/TKD mutated AML.
OUTLINE:
Beginning 30 days post-hematopoietic cell transplantation (HCT), patients receive midostaurin orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then up to 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Midostaurin | Experimental | Drug: MidostaurinBeginning 30 days post-HCT, participants receive oral midostaurin twice-a-day in 28-day treatment cycles, continuing up to 12 cycles in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Elderly patients with FLT3-mutated acute myeloid leukemia (AML)
- Prior enrollment in Stanford study IRB-25737
- In continued complete remission
- ≥ 30 days but ≤ 90 days post allogeneic hematopoietic cell transplant (HCT); treatment on this study protocol must begin before day 90 post-HCT
- Absolute neutrophil count (ANC) ≥ 1000 cells/uL
Key exclusion criteria (29 listed)
- Uncontrolled acute graft-vs-host disease (GVHD) grade 3 to 4
- Uncontrolled active infection
- Evidence of active AML (eg, circulating peripheral blasts on complete blood count)
- Known confirmed diagnosis of human immunodeficiency virus (HIV) infection
- Known confirmed diagnosis of active viral hepatitis
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 |
|---|---|---|
| MidostaurinAlso: Rydapt, CGP 41251, N-benzoyl-staurosporine, PKC-412Given PO | Drug | Midostaurin |
Primary outcome
Event-free survival
Time frame: Up to 1 year
Incidence of adverse events using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time frame: Up to 30 days
Overall survival
Time frame: Up to 1 year
Calculated and reported with Kaplan Meier curves. The statistical analyses will focus on estimation rather than hypothesis testing. Two-sided 95% confidence intervals will be presented, using the Clopper-Pearson method for proportions and using Greenwood's formula for time to event outcomes.
Relapse free survival
Time frame: Up to 1 year
Calculated and reported with Kaplan Meier curves. The statistical analyses will focus on estimation rather than hypothesis testing. Two-sided 95% confidence intervals will be presented, using the Clopper-Pearson method for proportions and using Greenwood's formula for time to event outcomes.
1 secondary outcome
Relapse rate after allogeneic transplant
Time frame: Up to 1 year
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2018.
- 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.
David Iberri, MD principal investigator
Stanford University
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Midostaurin in people with Acute Myeloid Leukemia With Gene Mutations and Adult Acute Myeloid Leukemia in Remission, run by Stanford University.
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 29 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: withdrawn, as of the sponsor's last update on 4 May 2018. Status can change between updates, so confirm with the study contact before making plans.
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Event-free survival (time frame: Up to 1 year). The study lists 4 primary outcomes in all. 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 4 May 2018.