Myelodysplastic SyndromesPhase 1/2NCT03929211
CPI-613 and Hydroxychloroquine for Patients With High Risk Myelodysplastic Syndrome
A Phase 1/2 study testing CPI-613 and Hydroxychloroquine in people with Myelodysplastic Syndromes and Progressive Disease, run by Wake Forest University Health Sciences at 2 sites in United States.
Trial summary
This is a phase 1/2 study of the combination of CPI-613 and hydroxychloroquine for the treatment of high risk myelodysplastic syndrome patients who have failed a hypomethylating agent. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes, Progressive Disease
- What is being tested?
- CPI-613 and Hydroxychloroquine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2021to Jul 2027
- Phase
- Phase 1/2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must meet all of the following inclusion criteria before enrollment:
- Histologically documented high risk MDS whose disease has failed to respond, progressed or relapsed while on a hypomethylating agent.
- IPSS-R score of Intermediate, high or very high at time of enrollment
- ECOG Performance Status of ≤3.
- Men and women 18 years of age or older.
- Expected survival >2 months.
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- Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device) during the study, and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation.
- Fertile men must practice effective contraceptive methods during the study, unless documentation of infertility exists.
- Patients must have fully recovered from the acute, non-hematological, non-infectious toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities. Patients with persisting, non-hematologic, non-infectious toxicities from prior treatment ≤ Grade 2 are eligible, but must be documented as such.
- Laboratory values obtained ≤2 weeks prior to enrollment must demonstrate adequate hepatic function, renal function, and coagulation as defined below:
- Aspartate aminotransferase [AST/SGOT] ≤3x upper normal limit [UNL]
- Alanine aminotransferase [ALT/SGPT] ≤3x UNL
- Bilirubin ≤1.5x UNL
- Serum creatinine ≤1.5 mg/dL or 133 μmol/L
- Albumin ≥ 2.0 g/dL or ≥ 20 g/L.
- Mentally competent, ability to understand and willingness to sign an IRB-approved written informed consent form.
- Have access via central line (e.g., portacath).
Who cannot join
- Patients with the following characteristics are excluded:
- Serious medical illness, such as significant cardiac disease (e.g. symptomatic congestive heart failure, unstable angina pectoris, symptomatic coronary artery disease, myocardial infarction within the past 3 months, uncontrolled cardiac arrhythmia, pericardial disease or New York Heart Association Class III or IV), or severe debilitating pulmonary disease, that would potentially increase patients' risk for toxicity.
- Patients with active central nervous system (CNS) or epidural tumor.
- Any active uncontrolled bleeding or bleeding diathesis (e.g., active peptic ulcer disease).
- Any condition or abnormality which may, in the opinion of the investigator, compromise his or her safety.
- Pregnant women, or women of child-bearing potential not using reliable means of contraception.
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- Fertile men unwilling to practice contraceptive methods during the study period.
- Lactating females.
- Life expectancy less than 2 months.
- Unwilling or unable to follow protocol requirements.
- Evidence of ongoing uncontrolled serious infection.
- Requirement for immediate palliative treatment of any kind including surgery.
- Patients with uncontrolled HIV infection. (Note: Patients with known HIV infection are excluded because patients with an immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, and because there may be unknown or dangerous drug interactions between CPI-613 and anti-retroviral agents used to treat HIV infections).
- Patients who have received radiotherapy, surgery, treatment with cytotoxic agents (except a hypomethylating agent, i.e. azacytidine or decitabine), treatment with biologic agents, immunotherapy, or any other anti-cancer therapy of any kind, or any other standard or investigational treatment for their cancer, or any other investigational agent for any indication, within the past 2 weeks prior to initiation of CPI-613 treatment.
- Patients that have received a chemotherapy regimen with stem cell support in the previous 6 months.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Roswell Park Cancer Institute
Buffalo, New York, 14263
Wake Forest Baptist Comprehensive Cancer Center
Winston-Salem, North Carolina, 27157
About this study
Official title: A Phase I/II Study of CPI-613 and Hydroxychloroquine for Patients With High Risk MDS Who Have Failed Hypomethylating Therapy
This is a phase 1/2 study of the combination of CPI-613 and hydroxychloroquine for the treatment of high risk myelodysplastic syndrome patients who have failed a hypomethylating agent.
Read the detailed description
Primary Objective(s):
- To determine the Maximum Tolerated Dose (MTD) of the combination of CPI-613 and Hydroxychloroquine therapy for patients with high risk MDS who have failed hypomethylating therapy.
- To determine the overall response rate (complete remission (CR), marrow CR, partial remission (PR), Hematologic improvement (HI)) of high risk MDS patients who have failed hypomethylating agents, treated with the combination of CPI-613 and the maximally tolerated dose of hydroxychloroquine
Secondary Objective(s):
- To assess the safety of the combination
- To assess progression-free-survival (PFS)
- To assess the overall survival of MDS patients who have failed hypomethylating agents treated with the combination of CPI-613 and hydroxychloroquine defined as the time from enrolment on study to death from any cause.
- To assess any changes in the frequency of blood transfusions
OUTLINE: This is a phase I, dose-escalation study of hydroxychloroquine, followed by a phase II study.
Patients receive hydroxychloroquine orally (PO) and 6,8-bis(benzylthio)octanoic acid intravenously (IV) over 2 hours on days 1-5. Treatments repeat every 14 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 3, patients receive hydroxychloroquine PO and 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 5 years.
- Conditions
- Myelodysplastic Syndromes, Progressive Disease
- Being tested
- CPI-613, Hydroxychloroquine
- Keywords
- Relapsed/refractory myelodysplastic syndrome, Failed hypomethylating therapy
- Medical subject headings
- Myelodysplastic Syndromes, Disease Progression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CPI-613Drug
Also called 6,8-Bis(benzylthio)octanoic Acid
Given intravenously, CPI-613 dose will be 2,000 mg/m² and will not escalate.
Also called 118-42-3, hydroxychloroquine, HYDROXYCHLOROQUINE, Hydroxychloroquine
Given by mouth, hydroxychloroquine will be dose escalated from 600 mg to 1,200 mg orally given 2 hours before the CPI-613 infusion on days 1-5 of every 28 day cycle in a 3+3 dose escalation design.
| Study group | Role | What they receive |
|---|---|---|
| CPI-613 and hydroxychloroquine | Experimental | The initial phase of the study will be a dose escalation of hydroxychloroquine from 600 mg to 1,200 mg orally flat dose given 2 hours before the CPI-613 infusion on days 1-5 of every 28 days. CPI-dose will be 2,000 mg/m² and will not be escalated. Receives: Drug: CPI-613; Drug: Hydroxychloroquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Dose Limiting Toxicities
Dose-limiting toxicities assessed in order to be able to establish the maximum tolerable dose for the combination of CPI-613 and Hydroxychloroquine therapy for patients with high risk myelodysplastic syndrome who have failed hypomethylating therapy. Using the descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 for adverse event reporting (Grade 1 (Mild) - 5 (Death) as well as expectedness (unexpected/expected) and attribution (definitely related to study treatment to unrelated to study treatment).
Measured: 4 weeks
Overall Response Rate
Measurements for response criteria will be based upon the Modified International Working Group (IWG) 2006 response criteria for altering natural history of myelodysplastic syndrome. Overall response rates criteria - complete remission (CR), partial response (PR) marrow CR, hematologic improvement (HI), or stable disease, failure, relapse after complete response or partial response, cytogenetic response, disease progression and survival) of high risk myelodysplastic syndrome patients who have failed hypomethylating agents treated with the combination of CPI-613 and the maximally tolerated dose of hydroxychloroquine.
Measured: 4 weeks
Secondary outcomes (4)
Proportion of Patients with Toxicities
Toxicity profiles of participants during the trial to assess the safety of the combination of CPI-613 and hydroxychloroquine will be presented in tables that describe the number and proportion of patients observed with toxicities.
Measured: 4 weeks
Progression-free-survival
Progression-free-survival is defined as the duration of time from the start of treatment to the time of progression, death, or date of last contact; those lost to follow-up will be censored. Kaplan-Meier survival curves to examine progression free survival in participants will be created.
Measured: Up to 5 years or until death
Overall Survival
Overall survival of myelodysplastic syndrome patients who have failed hypomethylating agents treated with the combination of CPI-613 and hydroxychloroquine defined as the time from enrollment on study to death from any cause.
Measured: Up to 5 years or until death
Changes in the Frequency of Blood Transfusions
The investigators will assess for each participant the number of blood transfusions needed and create tables to display the number and timing of blood transfusions that occur.
Measured: Baseline to approximately 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2019
- Study startMay 2021 (estimated)
- Primary completionSep 2022 (estimated)
- Study completionJul 2027 (estimated)
Why it stopped: Administrative withdrawal by IRB
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Bayard Powell, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03929211
- Sponsor's protocol ID
- IRB00057945
- Other IDs
- WFBCCC 99119, P30CA012197, NCI-2019-02787
- Status last verified
- Apr 2021
- First submitted
- 24 Apr 2019
- Last updated
- 14 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- 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 14 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of CPI-613 and Hydroxychloroquine for Patients With High Risk MDS Who Have Failed Hypomethylating Therapy
- ClinicalTrials.gov ID
- NCT03929211
- Acronym / sponsor ID
- IRB00057945
- Conditions
- Myelodysplastic Syndromes, Progressive Disease
- Keywords
- Relapsed/refractory myelodysplastic syndrome, Failed hypomethylating therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Administrative withdrawal by IRB
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- May 2021 (estimated)
- Primary completion
- Sep 2022 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 26 Apr 2019 (actual)
- 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 is a phase 1/2 study of the combination of CPI-613 and hydroxychloroquine for the treatment of high risk myelodysplastic syndrome patients who have failed a hypomethylating agent.
Detailed description
Primary Objective(s):
- To determine the Maximum Tolerated Dose (MTD) of the combination of CPI-613 and Hydroxychloroquine therapy for patients with high risk MDS who have failed hypomethylating therapy.
- To determine the overall response rate (complete remission (CR), marrow CR, partial remission (PR), Hematologic improvement (HI)) of high risk MDS patients who have failed hypomethylating agents, treated with the combination of CPI-613 and the maximally tolerated dose of hydroxychloroquine
Secondary Objective(s):
- To assess the safety of the combination
- To assess progression-free-survival (PFS)
- To assess the overall survival of MDS patients who have failed hypomethylating agents treated with the combination of CPI-613 and hydroxychloroquine defined as the time from enrolment on study to death from any cause.
- To assess any changes in the frequency of blood transfusions
OUTLINE: This is a phase I, dose-escalation study of hydroxychloroquine, followed by a phase II study.
Patients receive hydroxychloroquine orally (PO) and 6,8-bis(benzylthio)octanoic acid intravenously (IV) over 2 hours on days 1-5. Treatments repeat every 14 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 3, patients receive hydroxychloroquine PO and 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CPI-613 and hydroxychloroquine | Experimental | Drug: CPI-613, Drug: HydroxychloroquineThe initial phase of the study will be a dose escalation of hydroxychloroquine from 600 mg to 1,200 mg orally flat dose given 2 hours before the CPI-613 infusion on days 1-5 of every 28 days. CPI-dose will be 2,000 mg/m² and will not be escalated. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Histologically documented high risk MDS whose disease has failed to respond, progressed or relapsed while on a hypomethylating agent.
- IPSS-R score of Intermediate, high or very high at time of enrollment
- ECOG Performance Status of ≤3.
- Men and women 18 years of age or older.
- Expected survival >2 months.
Key exclusion criteria (15 listed)
- Patients with the following characteristics are excluded:
- Serious medical illness, such as significant cardiac disease (e.g. symptomatic congestive heart failure, unstable angina pectoris, symptomatic coronary artery disease, myocardial infarction within the past 3 months, uncontrolled cardiac arrhythmia, pericardial disease or New York Heart Association Class III or IV), or severe debilitating pulmonary disease, that would potentially increase patients' risk for toxicity.
- Patients with active central nervous system (CNS) or epidural tumor.
- Any active uncontrolled bleeding or bleeding diathesis (e.g., active peptic ulcer disease).
- Any condition or abnormality which may, in the opinion of the investigator, compromise his or her safety.
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 |
|---|---|---|
| CPI-613Also: 6,8-Bis(benzylthio)octanoic AcidGiven intravenously, CPI-613 dose will be 2,000 mg/m² and will not escalate. | Drug | CPI-613 and hydroxychloroquine |
| HydroxychloroquineAlso: 118-42-3, hydroxychloroquine, HYDROXYCHLOROQUINE, HydroxychloroquineGiven by mouth, hydroxychloroquine will be dose escalated from 600 mg to 1,200 mg orally given 2 hours before the CPI-613 infusion on days 1-5 of every 28 day cycle in a 3+3 dose escalation design. | Drug | CPI-613 and hydroxychloroquine |
Primary outcome
Number of Dose Limiting Toxicities
Time frame: 4 weeks
Dose-limiting toxicities assessed in order to be able to establish the maximum tolerable dose for the combination of CPI-613 and Hydroxychloroquine therapy for patients with high risk myelodysplastic syndrome who have failed hypomethylating therapy. Using the descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 for adverse event reporting (Grade 1 (Mild) - 5 (Death) as well as expectedness (unexpected/expected) and attribution (definitely related to study treatment to unrelated to study treatment).
Overall Response Rate
Time frame: 4 weeks
Measurements for response criteria will be based upon the Modified International Working Group (IWG) 2006 response criteria for altering natural history of myelodysplastic syndrome. Overall response rates criteria - complete remission (CR), partial response (PR) marrow CR, hematologic improvement (HI), or stable disease, failure, relapse after complete response or partial response, cytogenetic response, disease progression and survival) of high risk myelodysplastic syndrome patients who have failed hypomethylating agents treated with the combination of CPI-613 and the maximally tolerated dose of hydroxychloroquine.
4 secondary outcomes
Proportion of Patients with Toxicities
Time frame: 4 weeks
Progression-free-survival
Time frame: Up to 5 years or until death
Overall Survival
Time frame: Up to 5 years or until death
Changes in the Frequency of Blood Transfusions
Time frame: Baseline to approximately 6 months
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 14 Apr 2021.
- 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.
Bayard Powell, MD principal investigator
Wake Forest University Health Sciences
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CPI-613 and Hydroxychloroquine in people with Myelodysplastic Syndromes and Progressive Disease, run by Wake Forest University Health Sciences 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 17 inclusion and 15 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 14 Apr 2021. 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 combined 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.
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?
Number of Dose Limiting Toxicities (time frame: 4 weeks). The study lists 2 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 14 Apr 2021.