AMLPhase 1NCT04017546
CYC065 CDK Inhibitor and Venetoclax Study in Relapsed/Refractory AML or MDS
A Phase 1 study testing CYC065 and Venetoclax in people with AML and MDS, run by Cyclacel Pharmaceuticals, Inc. at 1 site in United States.
Trial summary
A Phase I Combination Study of CYC065 and Venetoclax for Relapsed or Refractory AML or MDS Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- CYC065 and Venetoclax
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Aug 2019to 5 Apr 2023
- Phase
- Phase 1
- 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
- Previously treated AML or MDS based on WHO classification and having at least 10% blasts in peripheral blood
- ECOG 0-2
- Adequate renal function
- Adequate liver function
- INR <=1.2 in patients not receiving chronic anticoagulation
- At least 2 weeks from prior cytotoxic chemotherapy, radiation therapy, major surgery or other investigational cancer therapy
- Agree to practice effective contraception
Who cannot join
- AML is of the subtype of APL or extramedullary myeloid tumor without bone marrow involvment
- Known AML involvement in CNS that is symptomatic and active
- Currently receiving radiotherapy, biological therapy, or any other investigational agents
- Uncontrolled intercurrent illness
- Pregnant or lactating
- Known to be HIV-positive
- Known active hepatitis B and/or hepatitis C infection
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Combination Study of CYC065 and Venetoclax in Patients with Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes
A Phase I Combination Study of CYC065 and Venetoclax for Relapsed or Refractory AML or MDS
Read the detailed description
This is an open-label, single arm, dose escalation study in patients with relapsed or refractory AML or MDS. Treatment will be administered on an outpatient basis and all patients will receive CYC065 over 4-hour infusion once every 2 weeks on Day 1 and Day 15 in combination with venetoclax. One treatment cycle is 4 weeks.
- Being tested
- CYC065, Venetoclax
- Keywords
- CYC065, CDK2/9, venetoclax, BCL-2, MCL-1, Relapsed, Refractory, acute myeloid leukemia, myelodysplastic syndromes, AML, MDS
- Medical subject headings
- Recurrence, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CYC065Drug
intravenous infusion
VenetoclaxDrug
oral capsule
| Study group | Role | What they receive |
|---|---|---|
| CYC065 and venetoclax | Experimental | CYC065 will be administered intravenously via 4-hour infusion on Day 1 and Day 15. Venetoclax will be taken daily on Day 1 through Day 15. One cycle will be 28 days or 4 weeks. Receives: Drug: CYC065; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD)
Number of patients who experience dose-limiting toxicity (DLT)
Measured: At the end of cycle 1 (each cycle is 28 days)
Secondary outcomes (2)
Pharmacokinetic effect
plasma drug level
Measured: At the end of cycle 1 (each cycle is 28 days)
Pharmacodynamic effect
MCL-1 level in peripheral white blood cells
Measured: At the end of cycle 1 (each cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2019
- Study start2 Aug 2019
- Primary completion15 Nov 2022
- Study completion5 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AMLStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- One to 6 patients will be entered at a given CYC065 dose level. Dose escalation will be 33% after at least one patient has completed the first treatment cycle without ≥ grade 2 toxicity considered by the investigator to be related to CYC065. Upon the first occurrence of grade 2 toxicity related to CYC065, at least 3 patients will be entered at each dose level. If no DLT is observed in any patients, dose escalation will continue to be 33%. If one of 3 patients experienced a DLT at a given dose level, dose escalation will continue at 25% until MTD is reached. If 2 or more patients experienced a DLT at a given dose level, dose escalation will be stopped. At least 6 patients will be treated at MTD.
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cyclacel Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gautam Borthakur, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04017546
- Sponsor's protocol ID
- CYC065-03
- Status last verified
- Sep 2024
- First submitted
- 8 Jul 2019
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Frame S, Saladino C, MacKay C, Atrash B, Sheldrake P, McDonald E, Clarke PA, Workman P, Blake D, Zheleva D. Fadraciclib (CYC065), a novel CDK inhibitor, targets key pro-survival and oncogenic pathways in cancer. PLoS One. 2020 Jul 9;15(7):e0234103. doi: 10.1371/journal.pone.0234103. eCollection 2020.
PubMed 32645016
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Combination Study of CYC065 and Venetoclax in Patients with Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes
- ClinicalTrials.gov ID
- NCT04017546
- Acronym / sponsor ID
- CYC065-03
- Keywords
- CYC065, CDK2/9, venetoclax, BCL-2, MCL-1, Relapsed, Refractory, acute myeloid leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Cyclacel Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 2 Aug 2019 (actual)
- Primary completion
- 15 Nov 2022 (actual)
- Study completion
- 5 Apr 2023 (actual)
- First posted
- 12 Jul 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.
A Phase I Combination Study of CYC065 and Venetoclax for Relapsed or Refractory AML or MDS
Detailed description
This is an open-label, single arm, dose escalation study in patients with relapsed or refractory AML or MDS. Treatment will be administered on an outpatient basis and all patients will receive CYC065 over 4-hour infusion once every 2 weeks on Day 1 and Day 15 in combination with venetoclax. One treatment cycle is 4 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- One to 6 patients will be entered at a given CYC065 dose level. Dose escalation will be 33% after at least one patient has completed the first treatment cycle without ≥ grade 2 toxicity considered by the investigator to be related to CYC065. Upon the first occurrence of grade 2 toxicity related to CYC065, at least 3 patients will be entered at each dose level. If no DLT is observed in any patients, dose escalation will continue to be 33%. If one of 3 patients experienced a DLT at a given dose level, dose escalation will continue at 25% until MTD is reached. If 2 or more patients experienced a DLT at a given dose level, dose escalation will be stopped. At least 6 patients will be treated at MTD.
| Arm | Type | Receives |
|---|---|---|
| CYC065 and venetoclax | Experimental | Drug: CYC065, Drug: VenetoclaxCYC065 will be administered intravenously via 4-hour infusion on Day 1 and Day 15. Venetoclax will be taken daily on Day 1 through Day 15. One cycle will be 28 days or 4 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Previously treated AML or MDS based on WHO classification and having at least 10% blasts in peripheral blood
- ECOG 0-2
- Adequate renal function
- Adequate liver function
- INR <=1.2 in patients not receiving chronic anticoagulation
Key exclusion criteria (7 listed)
- AML is of the subtype of APL or extramedullary myeloid tumor without bone marrow involvment
- Known AML involvement in CNS that is symptomatic and active
- Currently receiving radiotherapy, biological therapy, or any other investigational agents
- Uncontrolled intercurrent illness
- Pregnant or lactating
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 |
|---|---|---|
| CYC065intravenous infusion | Drug | CYC065 and venetoclax |
| Venetoclaxoral capsule | Drug | CYC065 and venetoclax |
Primary outcome
Maximum tolerated dose (MTD)
Time frame: At the end of cycle 1 (each cycle is 28 days)
Number of patients who experience dose-limiting toxicity (DLT)
2 secondary outcomes
Pharmacokinetic effect
Time frame: At the end of cycle 1 (each cycle is 28 days)
Pharmacodynamic effect
Time frame: At the end of cycle 1 (each cycle is 28 days)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Derived from this study: PubMed 32645016Frame S, Saladino C, MacKay C, Atrash B, Sheldrake P, McDonald E, Clarke PA, Workman P, Blake D, Zheleva D. Fadraciclib (CYC065), a novel CDK inhibitor, targets key pro-survival and oncogenic pathways in cancer. PLoS One. 2020 Jul 9;15(7):e0234103. doi: 10.1371/journal.pone.0234103. eCollection 2020.
- 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.
Gautam Borthakur, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CYC065 and Venetoclax in people with AML and MDS, run by Cyclacel Pharmaceuticals, Inc. 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 7 inclusion and 7 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 19 Sep 2024. 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 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.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum tolerated dose (MTD) (time frame: At the end of cycle 1 (each cycle is 28 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04017546, which also lists 1 linked publication.
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 19 Sep 2024.