A Study to Investigate Fadraciclib (CYC065), in Subjects With Leukemia or Myelodysplastic Syndrome (MDS)

NCT05168904 | Suspended Phase 1 DMC FDA Drug

• 1 other identifier: CYC065-102
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 2

Brief 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 therapy or for which no standard therapy exists.

Conditions

Leukemia; Myelodysplastic Syndrome(MDS)

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose

  The incidence rate of dose-limiting toxicities (first cycle only) at each dose level

  6 months

• Overall Response Rate (ORR)

  Assessment of response criteria according to iwCLL criteria for CLL/SLL and IWG criteria for AML and MDS.

  18 months

Secondary Outcomes (1)

• Adverse events

  24 months

Other Outcomes (3)

• Pharmacodynamics

  6 months

• Pharmacogenomics

  24 months

• Correlative studies

  24 months

Study Arms (2)

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.

Drug: fadraciclib

Phase 2

EXPERIMENTAL

Recommended fadraciclib phase 2 dose and schedule administered orally in 28-day cycles.

Drug: fadraciclib

Interventions

fadraciclib DRUG

Fadraciclib is a highly selective, orally- and intravenously- available, 2nd generation amino-purine inhibitor of CDK2 and CDK9.

Also known as: CYC065

Phase 2; Phase I Dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Cyclacel Pharmaceuticals, Inc.: lead

Study Sites (2)

City of Hope

Duarte, California, 91010, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes

Interventions

CYC065

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2021
• First Posted: December 23, 2021
• Study Start: October 22, 2021
• Primary Completion: October 1, 2024
• Study Completion: December 1, 2024
• Last Updated: February 8, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)