- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03760523
Dose Escalation Study of Minnelide in Relapsed or Refractory Acute Myeloid Leukemia
February 21, 2024 updated by: H. Lee Moffitt Cancer Center and Research Institute
Phase 1/1b Dose Escalation Study of Minnelide in Relapsed or Refractory Acute Myeloid Leukemia
This study is to determine the safety and recommended dosing of Minnelide in Acute Myeloid Leukemia (AML)
Study Overview
Detailed Description
This phase 1 dose escalation clinical trial will establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of Minnelide as single-agent in relapsed/refractory (R/R) acute myeloid leukemia (AML) patients who are ineligible to receive intensive chemotherapy.
The oral formulation of Minnelide will be used.
Minnelide is a prodrug of triptolide (a potent heat shock protein (HSP) 70 inhibitor) with promising preclinical activity in AML.
Study Type
Interventional
Enrollment (Actual)
27
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Florida
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Tampa, Florida, United States, 33612
- H. Lee Moffitt Cancer Center and Research Institute
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Adults ages 18 years or older.
- Participant must have relapsed or refractory acute myeloid leukemia (AML) (excluding acute promyelocytic leukemia).
- Relapsed patients must have received at least 1 induction chemotherapy regimen or two cycles of a hypomethylating agent and achieved a Complete Response (CR), followed by relapse of disease.
- Refractory patients must have received at least 1 induction chemotherapy regimen or two cycles of hypomethylating agent without achieving a CR.
- Eastern Cooperative Oncology Group (ECOG) performance status <2.
- Participants must have acceptable organ function.
- Be able and willing to adhere to the study visit schedule and other protocol requirements.
- Must be able to swallow capsules and have no evidence of GI tract abnormality that would alter the absorption of oral medications.
- The effects of Minnelide on the developing human fetus are unknown. For this reason, women of child-bearing potential must have a negative serum or urine pregnancy test within 24 hours prior to beginning study treatment.
- Participants of childbearing potential must practice contraception. Females of childbearing potential: Recommendation is for 2 effective contraceptive methods during the study. Male participants with female partners who are of childbearing potential: Recommendation is for male and partner to use at least 2 effective contraceptive methods, as described above, during the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Minnelide, breastfeeding mothers must agree to discontinue nursing if the mother is treated with Minnelide.
- Provision of signed and dated informed consent document
- Patients with prior allogeneic stem cell transplant who experience relapse of AML are eligible if they are off of immunosuppressive therapy and without any evidence of graft-versus-host disease (GVHD)
Exclusion Criteria:
- Participants may not have received any therapy with any investigational products, systemic anti-neoplastic therapy, or radiotherapy within 14 days prior to Cycle 1 Day 1. Patients actively receiving hydroxyurea are eligible and may continue to receive hydroxyurea during protocol treatment.
- Candidates for standard and/or potentially curative treatments.
- Major surgery within 28 days prior to Cycle 1 Day 1.
- New York Heart Association Class III or IV heart failure, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on an electrocardiogram (EKG)
- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
- Known, active HIV, Hepatitis A, B or C infection (prior Hepatitis C infection that has been treated and determined to be cured is allowed)
- Symptomatic central nervous system (CNS) involvement with leukemia
- A concurrent second active and non-stable malignancy with the exception of non-melanoma skin cancer or carcinoma in-situ.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Minnelide Dose Escalation
A 3+3 design will be used.
The first 3 patients will be treated at dose level 1.
If none experience a Dose Limiting Toxicity (DLT), the next 3 patients will be treated at dose level 2. If a DLT is observed in 1 out of 3 patients at dose level 1, up to an 3 more patients will be enrolled and treated at that dose level.
If 2 patients at dose level have DLTs, dosing will be lowered to dose level -1 (.5 mg daily, taken orally).
If 2 or more of the up to 6 patients at any dose level have DLTs, the preceding dose will be declared the Maximum Tolerated Dose (MTD).
If more than 1 DLT occurs at Dose Level -1, the investigators will consider stopping the study.
Once the MTD has been established, an additional 10 patients will be enrolled at this level to better characterize safety and tolerability.
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Patients will take Minnelide orally once daily on Days 1-21 of 28 day Cycle.
Dose Escalation Schedule: Dose Level -1: .5 mg, Dose Level 1: .75
mg, Dose Level 2: 1 mg, Dose Level 3: 1.25 mg.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose (MTD) of Minnelide
Time Frame: Up to 28 days for each dosing cohort
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MTD will be determined by testing increasing doses up to 1.25 mg daily.
MTD reflects highest dose of drug that did not cause a Dose Limiting Toxicity (DLT).
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Up to 28 days for each dosing cohort
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Number of Participants Who Experience Dose Limiting Toxicities (DLTs)
Time Frame: Up to 28 days for each dosing cohort
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A DLT is any Grade 3 or 4 drug-related non-hematologic toxicity, with some exceptions per protocol.
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Up to 28 days for each dosing cohort
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Complete Response (CR)
Time Frame: Up to 12 months
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Participants who experience Complete Response (CR) and Complete Response with Incomplete Blood Count Recovery (CRi) rate as defined by 2003 International Working Group (IWG) for AML.
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Up to 12 months
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Overall Response Rate (ORR)
Time Frame: Up to 12 months
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Overall Response Rate is defined as CR + CRi + partial response (PR) as defined by 2003 IWG criteria for AML.
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Up to 12 months
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Relapse Free Survival (RFS)
Time Frame: Up to 18 months
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RFS is defined as time interval between achievement of CR to time of relapse.
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Up to 18 months
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Overall Survival (OS)
Time Frame: Up to 12 months
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OS defined as time interval from time of enrollment onto the clinical trial to death from any cause.
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Up to 12 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Zhuoer Xie, MD, H. Lee Moffitt Cancer Center and Research Institute
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 18, 2019
Primary Completion (Actual)
October 9, 2023
Study Completion (Actual)
October 9, 2023
Study Registration Dates
First Submitted
November 27, 2018
First Submitted That Met QC Criteria
November 29, 2018
First Posted (Actual)
November 30, 2018
Study Record Updates
Last Update Posted (Actual)
February 22, 2024
Last Update Submitted That Met QC Criteria
February 21, 2024
Last Verified
February 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- MCC-19742
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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