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Bone Marrow Diseases

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CYC140 will be administered as a single agent on Day 1 and Day 8 of each 3 week cycle

CYC140

Mark Kirschbaum, MD

Hind Alazzawi

Gautam Borthakur, MD

A Phase I Pharmacologic Study of CYC140, a polo-like kinase 1 inhibitor, in Patients with Advanced Leukemias or Myelodysplastic Syndromes

This is a First in Human, open-label, single arm, dose escalation study in patients with advanced leukemias or myelodysplastic syndromes. Patients will receive CYC140 as a 1 hr infusion once a week for 2 weeks followed by 1 week of rest on an outpatient basis. One treatment cycle is 3 weeks.

One to three patients will be entered at a given dose level of CYC140. During the first cycle, all patients will be evaluated for DLTs. If DLT occurs, additional patients (up to 3) will be dosed at that dose. If no additional DLTs observed, dose escalation will continue per protocol. If a DLT does occur, dose escalation will be stopped. At least 6 patients will be treated at the RD to confirm its tolerability.

A Phase I Study of CYC140, a PLK-1 Inhibitor, in Advanced Leukemias or MDS

A Phase I Pharmacologic Study of CYC140, a Polo-like Kinase 1 Inhibitor, in Patients With Advanced Leukemias or Myelodysplastic Syndromes

plasma drug exposure area under the curve (AUC)

M.D. Anderson Cancer Center

Cyclacel Pharmaceuticals, Inc.

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Philadelphia Chromosome

Leukemia, Myeloid, Chronic-Phase

Myeloproliferative Disorders

Chronic Disease

Disease Attributes

Translocation, Genetic

Chromosome Aberrations

Chronic Graft Versus Host Disease

Myeloid Leukemia

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Imatinib Mesylate

Enrolled subjects will continue to administer Radotinib 400mg twice daily (800mg/day) orally every 12 hours at regular dosing hours for 12 months.

Dose modification is allowed if the subject cannot comply with the protocol-defined dosing schedule due to hematologic or non-hematologic toxicities and toxicities resolve within 28 days (within 42 days for hematologic toxicities). For radotinib, maximum 2 dose reductions will be allowed by stage to 600mg and to 400mg.

1. Brand name/manufacturer: Supect Cap./IL-YANG PHARM. Co., Ltd.
2. Active ingredient: radotinib HCl 106.8mg (100mg as radotinib) or HCl 213.6mg (200mg as radotinib)
3. Appearance and formulation: hard capsule with a light blue cap and a body containing pale yellow powder
4. Storage conditions: Store in an airtight light proof container at room temperature.

Radotinib HCl

Na Yun Kim

Kang Hi An

Dong-Wook Kim, MD

Dong-Wook Kim

Dong Wook Kim

In a multinational, multicenter, single-arm, open-label and Phase III Radotinib clinical study, chronic phase Ph+ chronic myeloid leukemia patients with failure or intolerance to previous TKIs therapy including Imatinib will be recruited. In this phase 3 study, 173 subjects are expected to be enrolled in a single arm with the administration of Radotinib 400mg twice daily, which includes 10% of dropout rate.

A Phase 3 Study for the Efficacy and Safety of Radotinib in CP-CML Patients With Failure or Intolerance to Previous TKIs

A Phase 3 Multinational, Multi-center, Single-arm, Open-label Study for the Efficacy and Safety of Radotinib in Ph+ Chronic Phase Chronic Myeloid Leukemia Patients With Failure or Intolerance to Previous TKIs Therapy Including Imatinib

Incidence rate of BCR-ABL1 point mutations that are newly found during the course of radotinib treatment

To measure the concentration of radotinib in blood

Toxicities will be evaluated in all subjects treated with radotinib.

MCyR is defined as 0\~35% CCyR+PCyR based on ≥20 metaphase myelocytes. Chromosome test results from \<20 metaphase myelocytes will be excluded from the analysis.

CCyR is defined as complete loss of Ph chromosome based on ≥20 metaphase myelocytes. Chromosome test results from \<20 metaphase myelocytes will be excluded from the analysis.

MMR is defined as a ≥3-log reduction in BCR-ABL1 transcript level from the standardized reference or BCR-ABL1/ABL % of ≤0.1% according to the international reference when the level of BCR-ABL1 gene was measured by RQ-PCR, a standardized quantitative genetic method.

OS is defined as the duration from the first day of Radotinib administration to the day of death for certain causes.

PFS is defined as the duration from the first day of Radotinib administration to the earliest day of disease progression or death for certain causes.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase I Study of CYC140, a PLK-1 Inhibitor, in Advanced Leukemias or MDS	NCT03884829	AML, Adult Myelodysplastic... ALL, Adult CML, Refractory CLL, Refractory	CYC140	18 Years -	Cyclacel Pharmaceuticals, Inc.
A Phase I Study of CYC140, a PLK-1 Inhibitor, in Advanced Leukemias or MDS	NCT03884829	AML, Adult Myelodysplastic... ALL, Adult CML, Refractory CLL, Refractory	CYC140	18 Years -	Cyclacel Pharmaceuticals, Inc.
A Phase 3 Study for the Efficacy and Safety of Radotinib in CP-CML Patients With Failure or Intolerance to Previous TKIs	NCT03459534	Chronic Myeloid... CML, Chronic Ph... CML, Refractory CML - Philadelp...	Radotinib HCl	18 Years -	Il-Yang Pharm. Co., Ltd.

Spots Global Cancer Trial Database for cml, refractory