LeukemiaPhase 1/2NCT05168904
A Study to Investigate Fadraciclib (CYC065), in Subjects With Leukemia or Myelodysplastic Syndrome (MDS)
A Phase 1/2 study testing fadraciclib in people with Leukemia and Myelodysplastic Syndrome(MDS), run by Cyclacel Pharmaceuticals, Inc. at 2 sites in United States.
Trial summary
This is a 2-part, phase 1/2, open-label, multicenter study designed to evaluate the safety and efficacy of fadraciclib (formerly CYC065) administered orally BID. This study consists of Phase 1 and Phase 2 components in subjects with Leukemia or Myelodysplastic syndrome (MDS) who have progressed despite having standard… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Myelodysplastic Syndrome(MDS)
- What is being tested?
- fadraciclib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 210 participants
- Where
- 2 sitesUnited States
- Study dates
- 22 Oct 2021to Dec 2024
- 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
- Males or females aged ≥ 18 years.
- a) AML/MDS with blasts > 10% in subjects who have had an inadequate response or progression to venetoclax combinations with either HMA or low dose Ara-C or similar venetoclax combinations. or b. CLL in subjects who have received at least 2 lines of therapy, including venetoclax and a BTK inhibitor, who require therapy as per iwCLL criteria.
- Any prior therapy must have been completed at least 2 weeks prior to enrollment on this protocol, and the participant must have recovered to eligibility levels from prior toxicity
- Hydroxyurea may be used for the first 14 days of Cycle 1 for peripheral blast control. Valproic acid not being used for seizure control should be stopped 72 hours before starting treatment with fadraciclib.
- Any prior therapy with decitabine or azacitidine must have been completed at least 3 weeks prior to enrollment on this protocol.
- Subjects who relapsed post-autologous or post-allogeneic transplant are eligible. Post-transplant subjects must be without active fungal disease or significant acute graft-versus-host disease.
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- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Women of childbearing potential (WOCBP) must have a negative pregnancy test (urine or serum) within 7 days prior to starting the study drug. Both males and females must agree to use effective birth control during the study (prior to receiving the first dose and for 6 months after the last dose) if conception is possible during this interval.
- Subjects must be able to swallow and retain orally administered medication and not have any clinically significant GI abnormalities that may alter the absorption, such as malabsorption syndrome or major resection of the stomach or bowels.
- Subjects must be able to agree to and sign the informed consent and to comply with the protocol.
Who cannot join
- Subjects with known active leptomeningeal involvement by AML.
- Subjects who have not received vaccines for SARS-COV-2 within the last 3 months and have suspected signs and symptoms of COVID-19 or a recent history (within 14 days) of contact with any COVID-19 positive subject/isolation/quarantine or subjects with confirmed COVID-19.
- Subjects with a history of another primary malignancy, other than:
- Carcinomas in situ, e.g., breast, cervix, and prostate
- Locally excised non-melanoma skin cancer
- No evidence of disease from another primary cancer for 2 or more years and has not taken any anticancer treatment in 2 years.
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- Any other clinically significant acute or chronic medical or psychiatric condition or any laboratory abnormality that may increase the risk associated with study drug administration or may interfere with the interpretation of study results.
- Diseases that significantly affect GI absorption of fadraciclib.
- Subjects who have impaired cardiac function or clinically significant cardiac disease.
- Presence of active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or GI perforation within 6 months of enrollment.
- Presence of an active infection requiring IV antibiotics.
- Presence of known history of human immunodeficiency virus-1/2 with uncontrolled viral load and on medications that may interfere with metabolism.
- Presence of active hepatitis B virus (HBV) or hepatitis C virus (HCV).
- Subject has received systemic anticancer therapy (including investigational therapy), radiotherapy, or immunotherapy < 14 days or 5 half-lives (whichever is shorter) prior to administration of Dose 1 of study drug on Day 1 or have not recovered from the side effects of such therapy.
- Major surgery/surgical therapy for any cause within 4 weeks of the first dose.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
City of Hope
Duarte, California, 91010
MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: A Phase 1/2, Open Label, Multicenter Study to Investigate the Safety and Efficacy of Fadraciclib (CYC065), an Oral CDK 2/9 Inhibitor, in Subjects With Leukemias or Myelodysplastic Syndrome (MDS)
This is a 2-part, phase 1/2, open-label, multicenter study designed to evaluate the safety and efficacy of fadraciclib (formerly CYC065) administered orally BID. This study consists of Phase 1 and Phase 2 components in subjects with Leukemia or Myelodysplastic syndrome (MDS) who have progressed despite having standard therapy or for which no standard therapy exists.
Read the detailed description
Phase 1 part of the study will consist of a dose-escalation and a dose-finding component.
Phase 2 will enroll subjects AML, CLL, or MDS, into 7 groups:
Group 1: Subjects with AML or MDS having marrow blasts over > 10%, who have experienced an inadequate response or progression on venetoclax combinations with either HMAs or low dose Ara-C or similar venetoclax combinations
Group 2: Fadraciclib: Subjects with AML or MDS relapsed/refractory having marrow blasts over > 10% with FLT3, KIT, MAPK pathway (N and K RAS, BRAF, PTPN11, NF1) mutations after at least 1 line of prior therapy.
Group 3: Fadraciclib: Subjects with CLL who have progressed on 2 or more lines of therapy, including a Bruton's tyrosine kinase (BTK) inhibitor and venetoclax.
Group 4: Fadraciclib plus azacitidine: Subjects with AML or MDS who have progressed after therapy with an HMA.
Group 5: Fadraciclib plus venetoclax: Subjects with AML or MDS who have progressed after therapy with venetoclax.
Group 6: Fadraciclib plus venetoclax: Subjects with CLL or small lymphocytic lymphoma (SLL) who have progressed after therapy with venetoclax.
Group 7: Basket cohort: Leukemia types suspected to have a related mechanism of action such as MCL1, or MYC amplification/over-expression not included in previous groups
- Conditions
- Leukemia, Myelodysplastic Syndrome(MDS)
- Being tested
- fadraciclib
- Medical subject headings
- Leukemia, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fadraciclibDrug
Also called CYC065
Fadraciclib is a highly selective, orally- and intravenously- available, 2nd generation amino-purine inhibitor of CDK2 and CDK9.
| Study group | Role | What they receive |
|---|---|---|
| Phase I Dose escalation | Experimental | Phase 1 = fadraciclib administered orally in escalating doses starting at 50mg bid MWF for 3 weeks of a 4-week cycle. Subsequent cohorts will escalate in dose and schedule until optimized phase 2 dose and schedule is achieved. Receives: Drug: fadraciclib |
| Phase 2 | Experimental | Recommended fadraciclib phase 2 dose and schedule administered orally in 28-day cycles. Receives: Drug: fadraciclib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose
The incidence rate of dose-limiting toxicities (first cycle only) at each dose level
Measured: 6 months
Overall Response Rate (ORR)
Assessment of response criteria according to iwCLL criteria for CLL/SLL and IWG criteria for AML and MDS.
Measured: 18 months
Secondary outcomes (1)
Adverse events
Type, frequency, and severity of adverse drug reactions
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2021
- Study start22 Oct 2021
- Primary completionOct 2024 (estimated)
- Study completionDec 2024 (estimated)
Why it stopped: Slow enrollment and financial limitations
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 210 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cyclacel Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05168904
- Sponsor's protocol ID
- CYC065-102
- Status last verified
- Feb 2024
- First submitted
- 9 Dec 2021
- Last updated
- 8 Feb 2024
- 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 8 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2, Open Label, Multicenter Study to Investigate the Safety and Efficacy of Fadraciclib (CYC065), an Oral CDK 2/9 Inhibitor, in Subjects With Leukemias or Myelodysplastic Syndrome (MDS)
- ClinicalTrials.gov ID
- NCT05168904
- Acronym / sponsor ID
- CYC065-102
- Conditions
- Leukemia, Myelodysplastic Syndrome(MDS)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Slow enrollment and financial limitations
- Enrolment
- 210 participants (estimated)
- Lead sponsor
- Cyclacel Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 22 Oct 2021 (actual)
- Primary completion
- Oct 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 23 Dec 2021 (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 2-part, phase 1/2, open-label, multicenter study designed to evaluate the safety and efficacy of fadraciclib (formerly CYC065) administered orally BID. This study consists of Phase 1 and Phase 2 components in subjects with Leukemia or Myelodysplastic syndrome (MDS) who have progressed despite having standard therapy or for which no standard therapy exists.
Detailed description
Phase 1 part of the study will consist of a dose-escalation and a dose-finding component.
Phase 2 will enroll subjects AML, CLL, or MDS, into 7 groups:
Group 1: Subjects with AML or MDS having marrow blasts over > 10%, who have experienced an inadequate response or progression on venetoclax combinations with either HMAs or low dose Ara-C or similar venetoclax combinations
Group 2: Fadraciclib: Subjects with AML or MDS relapsed/refractory having marrow blasts over > 10% with FLT3, KIT, MAPK pathway (N and K RAS, BRAF, PTPN11, NF1) mutations after at least 1 line of prior therapy.
Group 3: Fadraciclib: Subjects with CLL who have progressed on 2 or more lines of therapy, including a Bruton's tyrosine kinase (BTK) inhibitor and venetoclax.
Group 4: Fadraciclib plus azacitidine: Subjects with AML or MDS who have progressed after therapy with an HMA.
Group 5: Fadraciclib plus venetoclax: Subjects with AML or MDS who have progressed after therapy with venetoclax.
Group 6: Fadraciclib plus venetoclax: Subjects with CLL or small lymphocytic lymphoma (SLL) who have progressed after therapy with venetoclax.
Group 7: Basket cohort: Leukemia types suspected to have a related mechanism of action such as MCL1, or MYC amplification/over-expression not included in previous groups
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase I Dose escalation | Experimental | Drug: fadraciclibPhase 1 = fadraciclib administered orally in escalating doses starting at 50mg bid MWF for 3 weeks of a 4-week cycle. Subsequent cohorts will escalate in dose and schedule until optimized phase 2 dose and schedule is achieved. |
| Phase 2 | Experimental | Drug: fadraciclibRecommended fadraciclib phase 2 dose and schedule administered orally in 28-day cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Males or females aged ≥ 18 years.
- a) AML/MDS with blasts > 10% in subjects who have had an inadequate response or progression to venetoclax combinations with either HMA or low dose Ara-C or similar venetoclax combinations. or b. CLL in subjects who have received at least 2 lines of therapy, including venetoclax and a BTK inhibitor, who require therapy as per iwCLL criteria.
- Any prior therapy must have been completed at least 2 weeks prior to enrollment on this protocol, and the participant must have recovered to eligibility levels from prior toxicity
- Hydroxyurea may be used for the first 14 days of Cycle 1 for peripheral blast control. Valproic acid not being used for seizure control should be stopped 72 hours before starting treatment with fadraciclib.
- Any prior therapy with decitabine or azacitidine must have been completed at least 3 weeks prior to enrollment on this protocol.
Key exclusion criteria (15 listed)
- Subjects with known active leptomeningeal involvement by AML.
- Subjects who have not received vaccines for SARS-COV-2 within the last 3 months and have suspected signs and symptoms of COVID-19 or a recent history (within 14 days) of contact with any COVID-19 positive subject/isolation/quarantine or subjects with confirmed COVID-19.
- Subjects with a history of another primary malignancy, other than:
- Any other clinically significant acute or chronic medical or psychiatric condition or any laboratory abnormality that may increase the risk associated with study drug administration or may interfere with the interpretation of study results.
- Diseases that significantly affect GI absorption of fadraciclib.
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 |
|---|---|---|
| fadraciclibAlso: CYC065Fadraciclib is a highly selective, orally- and intravenously- available, 2nd generation amino-purine inhibitor of CDK2 and CDK9. | Drug | Phase 2, Phase I Dose escalation |
Primary outcome
Maximum tolerated dose
Time frame: 6 months
The incidence rate of dose-limiting toxicities (first cycle only) at each dose level
Overall Response Rate (ORR)
Time frame: 18 months
Assessment of response criteria according to iwCLL criteria for CLL/SLL and IWG criteria for AML and MDS.
1 secondary outcome
Adverse events
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2024.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
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 fadraciclib in people with Leukemia and Myelodysplastic Syndrome(MDS), run by Cyclacel Pharmaceuticals, Inc. 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 10 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: paused, as of the sponsor's last update on 8 Feb 2024. 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?
Results are not available in the source record.
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 (time frame: 6 months). 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 8 Feb 2024.