MDSPhase 1/2NCT04109690
CPX-351 in Patients Treated for Higher-risk Myelodysplastic Syndromes Experiencing Hypomethylating Agent Failure.
A Phase 1/2 study testing CPX-351 in people with MDS, run by Yale University at 1 site in United States.
Trial summary
The proposed study is of a Liposomal formulation of cytarabine and daunorubicin (CPX-351) in patients treated for higher-risk myelodysplastic syndromes (MDS) experiencing hypomethylating agent failure. Read more about this study
- Who is it for?
- Ages 18 to 78 years
- Conditions the study is for
- MDS
- What is being tested?
- CPX-351
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Dec 2019to 27 Jul 2021
- 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 to 78 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with a diagnosis of MDS o (according to World Health Organization 2016 classification) made prior to administration off HMA
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2
- Patient must have recovered from toxicities of any prior treatment regimen (no CTCAE grading over 1 for non-hematological toxicities and a return to baseline for hematological values)
- Patient is considered eligible for chemotherapy (at discretion of local investigator)
- Patient must have been treated with a hypomethylating agent (+/- other agents) and
- be treated for at least 4 cycles (16 weeks) and have a stable marrow disease (no response) or
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- progressed without prior response based on MDS International Working Group (IWG) 2006 response criteria or
- relapsed after an initial response based on MDS IWG 2006 response criteria.
- Adequate liver and renal function:
- Estimated creatinine clearance above 40 ml/min
- Total bilirubin ≤ 1.5 x the Upper Limit of Normal (ULN) or ≤ 3.0 x the ULN unless considered due to Gilbert's syndrome,
- Alanine aminotransferase (ALT) (SGPT), and aspartate aminotransferase (AST) (SGOT) ≤ 2.5 x the ULN. For patients with hepatic leukemic involvement Alanine aminotransferase (ALT) (SGPT), and aspartate aminotransferase (AST) (SGOT) ≤ 5.0 x the ULN t
- Able to understand and sign the written informed consent
- Serum or urine pregnancy test (for female patients of childbearing potential) with a minimum sensitivity of 25 IU/L or equivalent units of human chorionic gonadotropin (HCG) negative at screening.
- Males and female patients both of childbearing potential and at risk for pregnancy must agree to use two highly effective method(s) of contraception throughout the study and for 180 days after the last dose of CPX-351 whichever occurs later.
- Female patients who are not of childbearing potential (i.e. meet at least 1 of the following criteria):
- Have undergone a documented hysterectomy and/or bilateral oophorectomy;
- Have medically confirmed ovarian failure;
- Have achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed by having a serum follicle stimulating hormone (FSH) level within the laboratory's reference range for postmenopausal women.
Who cannot join
- Any prior induction chemotherapy (defined as treatment with standard or high dose cytarabine in combination with an anthracycline and/or other agents)
- Any investigational agent administered within a month prior to inclusion or within 5 half-lives of the investigational agent whichever is longer.
- Promyelocytic acute leukemia and core binding factor acute leukemia.
- Active Central nervous system (CNS) disease
- Any severe chronic disease potentially interfering with the protocol including HIV infection, active or chronic hepatitis B or C. Testing will be completed during screening period.
- Any significant social condition that could limit the understanding of the study or the compliance to the protocol including but not limited to severe or uncontrolled psychiatric illness.
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- Any sign of active uncontrolled disease including but not restricted to cardiac disease, infections and platelet refractoriness.
- Any other malignancy with active treatment within the past 1 year other than basal cell skin cancer or carcinoma in situ of the cervix.
- New York Heart Association (NYHA) grade 3 or 4 cardiac failure, or left ventricular ejection fraction (LVEF) below 50%
- Patients who have received a cumulative dose of anthracyclines superior to a total of 300mg/m2 of daunorubicin in the absence of prior mediastinal radiation or 150mg/m2 if the patient had a prior mediastinal radiation
- Oxygen dependency as defined by a chronic need of oxygen at least 2l/min for at least 6h a day.
- Women who are pregnant, planning to become pregnant, or who are currently breastfeeding
- Persistence of any clinically relevant (CTCAE grade 2 or above) toxicities from previous therapy
- Any other condition that, according to the investigator, may forbid the administration of CPX-351
- Hypersensitivity to cytarabine, daunorubicin or liposomal products
- History of Wilson's disease or another copper-metabolism disorder
- Major injuries and/or surgery within the past 4 weeks prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period.
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale University; Smilow Cancer Center
New Haven, Connecticut, 06519
About this study
Official title: A Phase I-II Study of a Liposomal Formulation of Cytarabine and Daunorubicin (CPX-351) in Patients Treated for Higher-risk Myelodysplastic Syndromes Experiencing Hypomethylating Agent Failure.
The proposed study is of a Liposomal formulation of cytarabine and daunorubicin (CPX-351) in patients treated for higher-risk myelodysplastic syndromes (MDS) experiencing hypomethylating agent failure.
Read the detailed description
Proposed is a two-phase study. The Phase I portion will confirm the tolerability and safety of CPX-351 chemotherapy. Patients who meet eligibility criteria will receive dose level 1 of CPX-351 (44mg/m2 of daunorubicin and 100mg/m2 of cytarabine) on 2 days (day 1 and day 5) of the cycle.
If less than 2 dose limiting toxicity (DLT) are observed in the first cohort of 6, we will increase level of exposure to Dose Level 2 by giving (44mg/m2 of daunorubicin and 100mg/m2 of cytarabine) on days 1, 3 and 5 of
- If less than 2 DLTs are observed Dose Level 2 will become the Recommended Phase II dose (RP2D)
- If 2 or more DLTs are observed Dose Level 1 will become the RP2D If 2 or more DLTs are observed in the first cohort of 6 patients, another 6 patients will be enrolled at dose level -1 (29mg/m2 of daunorubicin and 65mg/m2 of cytarabine) on day 1 and 5.
- If less than 2 DLTs are observed Dose Level -1 will become the RP2D
- If 2 or more patients experience a DLT at dose -1 the study will be stopped Patients failing to achieve a response after cycle 1 will be offered a second cycle of induction with for dose level 1 and 2 (44mg/m2 of daunorubicin and 100mg/m2 of cytarabine) on day 1 and 5 of induction 2. And for dose level-1, (29mg/m2 of daunorubicin and 65mg/m2 of cytarabine) on day 1 and 5 of induction 2.
Phase II: Once the RP2D is confirmed we will enroll 12 patients. If 3 or more responses are observed an additional 12 patients will be enrolled for a total of 24. If 7 out of 24 evaluable patients achieve response, an additional 24 patients will be enrolled for a total of 48 patients.
- If less than 3 responses are observed in the first 12 patients, the study will be terminated.
The outcomes presented in this protocol are associated with the Phase II of the study.
- Conditions
- MDS
- Being tested
- CPX-351
- Keywords
- MDS
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CPX-351Drug
Patients in both Phase I and II can receive a maximum of two induction and six consolidation cycles on an inpatient or outpatient basis per local hospital standard of care.
| Study group | Role | What they receive |
|---|---|---|
| CPX-351 | Experimental | Phase I will evaluate the safety and tolerability of CPX-351 (44mg/m2 of daunorubicin and 100mg/m2 of cytarabine) administered on 2 days (day 1 and day 5) to determine the Phase II dose. Phase II will evaluate the efficacy of the RP2D. Receives: Drug: CPX-351 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
The Phase II primary objective is to determine the overall response rate (CR/CRi) of CPX-351 in MDS patients experiencing hypomethylation (HMA) failure.
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2019
- Study start30 Dec 2019
- Primary completion27 Jul 2021
- Study completion27 Jul 2021
Why it stopped: Failure to enroll
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MDSStudies of the same condition, open and under way.
- More trials run by Yale 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 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
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Thomas Prebet, MD, PHD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04109690
- Sponsor's protocol ID
- 2000024262
- Status last verified
- Jan 2022
- First submitted
- 27 Sep 2019
- Last updated
- 24 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I-II Study of a Liposomal Formulation of Cytarabine and Daunorubicin (CPX-351) in Patients Treated for Higher-risk Myelodysplastic Syndromes Experiencing Hypomethylating Agent Failure.
- ClinicalTrials.gov ID
- NCT04109690
- Acronym / sponsor ID
- 2000024262
- Conditions
- MDS
- Keywords
- MDS
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Failure to enroll
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- 30 Dec 2019 (actual)
- Primary completion
- 27 Jul 2021 (actual)
- Study completion
- 27 Jul 2021 (actual)
- First posted
- 30 Sep 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.
The proposed study is of a Liposomal formulation of cytarabine and daunorubicin (CPX-351) in patients treated for higher-risk myelodysplastic syndromes (MDS) experiencing hypomethylating agent failure.
Detailed description
Proposed is a two-phase study. The Phase I portion will confirm the tolerability and safety of CPX-351 chemotherapy. Patients who meet eligibility criteria will receive dose level 1 of CPX-351 (44mg/m2 of daunorubicin and 100mg/m2 of cytarabine) on 2 days (day 1 and day 5) of the cycle.
If less than 2 dose limiting toxicity (DLT) are observed in the first cohort of 6, we will increase level of exposure to Dose Level 2 by giving (44mg/m2 of daunorubicin and 100mg/m2 of cytarabine) on days 1, 3 and 5 of
- If less than 2 DLTs are observed Dose Level 2 will become the Recommended Phase II dose (RP2D)
- If 2 or more DLTs are observed Dose Level 1 will become the RP2D If 2 or more DLTs are observed in the first cohort of 6 patients, another 6 patients will be enrolled at dose level -1 (29mg/m2 of daunorubicin and 65mg/m2 of cytarabine) on day 1 and 5.
- If less than 2 DLTs are observed Dose Level -1 will become the RP2D
- If 2 or more patients experience a DLT at dose -1 the study will be stopped Patients failing to achieve a response after cycle 1 will be offered a second cycle of induction with for dose level 1 and 2 (44mg/m2 of daunorubicin and 100mg/m2 of cytarabine) on day 1 and 5 of induction 2. And for dose level-1, (29mg/m2 of daunorubicin and 65mg/m2 of cytarabine) on day 1 and 5 of induction 2.
Phase II: Once the RP2D is confirmed we will enroll 12 patients. If 3 or more responses are observed an additional 12 patients will be enrolled for a total of 24. If 7 out of 24 evaluable patients achieve response, an additional 24 patients will be enrolled for a total of 48 patients.
- If less than 3 responses are observed in the first 12 patients, the study will be terminated.
The outcomes presented in this protocol are associated with the Phase II of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CPX-351 | Experimental | Drug: CPX-351Phase I will evaluate the safety and tolerability of CPX-351 (44mg/m2 of daunorubicin and 100mg/m2 of cytarabine) administered on 2 days (day 1 and day 5) to determine the Phase II dose. Phase II will evaluate the efficacy of the RP2D. |
Who may qualify
- Ages
- 18 to 78 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Patients with a diagnosis of MDS o (according to World Health Organization 2016 classification) made prior to administration off HMA
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2
- Patient must have recovered from toxicities of any prior treatment regimen (no CTCAE grading over 1 for non-hematological toxicities and a return to baseline for hematological values)
- Patient is considered eligible for chemotherapy (at discretion of local investigator)
- Patient must have been treated with a hypomethylating agent (+/- other agents) and
Key exclusion criteria (17 listed)
- Any prior induction chemotherapy (defined as treatment with standard or high dose cytarabine in combination with an anthracycline and/or other agents)
- Any investigational agent administered within a month prior to inclusion or within 5 half-lives of the investigational agent whichever is longer.
- Promyelocytic acute leukemia and core binding factor acute leukemia.
- Active Central nervous system (CNS) disease
- Any severe chronic disease potentially interfering with the protocol including HIV infection, active or chronic hepatitis B or C. Testing will be completed during screening period.
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 |
|---|---|---|
| CPX-351Patients in both Phase I and II can receive a maximum of two induction and six consolidation cycles on an inpatient or outpatient basis per local hospital standard of care. | Drug | CPX-351 |
Primary outcome
Overall Response Rate
Time frame: Up to 24 months
The Phase II primary objective is to determine the overall response rate (CR/CRi) of CPX-351 in MDS patients experiencing hypomethylation (HMA) failure.
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 24 Jan 2022.
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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.
Thomas Prebet, MD, PHD principal investigator
Yale University
1 site 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 CPX-351 in people with MDS, run by Yale University at 1 site 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 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: withdrawn, as of the sponsor's last update on 24 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 1 site 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?
Overall Response Rate (time frame: Up to 24 months). 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 24 Jan 2022.