A Phase I/Ib, Open-label Study to Evaluate the Safety, Pharmacokinetics and Clinical Activity of RP7214, a Dihydro-orotate Dehydrogenase (DHODH) Inhibitor, Administered Orally in Combination With Azacitidine in Patients With Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia and Acute Myeloid Leukemia

Rhizen Pharmaceuticals SA0 sitesJanuary 2023

ConditionsMyelodysplastic Syndromes Chronic Myelomonocytic Leukemia Acute Myeloid Leukemia

InterventionsRP7214

DrugsRP7214

Overview

Phase: Phase 1
Intervention: RP7214
Conditions: Myelodysplastic Syndromes
Sponsor: Rhizen Pharmaceuticals SA
Primary Endpoint: Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of RP7214 in combination with azacitidine
Status: Withdrawn
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

This is a multi-center, open-label, non-randomized, two-part Phase I/Ib study of RP7214 in combination with azacitidine in patients with AML, MDS and CMML. Part I is a 3+3 dose-escalation study to identify the MTD/RP2D of RP7214 and azacitidine combination in patients with AML, MDS, and CMML. Part II is a dose-expansion study to evaluate the clinical activity and safety of RP7214 and azacitidine combination in AML.

Registry

clinicaltrials.gov

Start Date

January 2023

End Date

November 2025

Last Updated

3 years ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Rhizen Pharmaceuticals SA

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patient must sign informed consent.
•Patient should be ≥ 18 years of age.
•Patients who are candidates for treatment with azacitidine and present with one of the following:
•a. Part I: Dose Escalation study i. Patient with histologically or cytologically confirmed relapsed/refractory AML as per World Health Organization (WHO) classification, 2016 'OR' ii. Newly diagnosed AML patients who are ineligible for intensive induction chemotherapy due to co-morbidity or other factors 'OR' iii. Intermediate-2 or high-risk MDS according to the International Prognostic Scoring System (IPSS) 'OR' iv. Chronic Myelomonocytic Leukemia (CMML) b. Part II: Dose Expansion study i. Newly diagnosed AML patients who are ineligible for intensive induction chemotherapy due to co-morbidity or other factors.
•Patient should have an Eastern Cooperative Oncology Group (ECOG) Performance score of 0 to
•Patients must be amenable to serial bone marrow biopsies/aspirates and peripheral blood sampling as required by the protocol.

Exclusion Criteria

•Any cancer-directed therapy taken (e.g., chemotherapy, immunotherapy, biologic therapy or an investigational drug) within 14 days or 5 half-lives, whichever is shorter, prior to C1D
•For radiation therapy, at least 60 days should elapse from prior Total Body Irradiation (TBI) and at least 14 days from local palliative radiation therapy.
•Patients with rapidly increasing peripheral blast counts (WBC count \> 25,000/μL) while on hydroxyurea prior to C1D
•Patients with Acute Promyelocytic Leukemia (French American-British Class M3 AML).
•Patients on immunosuppressive therapy post autologous or allogeneic stem cell transplantation (ASCT or Allo-SCT) at the time of screening, or with clinically significant Graft-Versus-Host Disease (GVHD) in the opinion of the Investigator or has not recovered from transplant-associated toxicities prior to C1D
•Patient who discontinued prior therapy with DHODH inhibitors or azacitidine due to drug-related toxicity.
•Evidence of uncontrolled/progressing infection.
•Patients with immediate life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or Disseminated Intravascular Coagulation (DIC).
•Presence of isolated extramedullary relapse.
•Pregnant or lactating women

Arms & Interventions

Part I (dose escalation) RP7214 + Azacitidine

Participants will receive RP7214 orally in combination with Azacitidine in a 28-day cycle. The dose levels will be escalated until MTD/a recommended Phase 2 dose (RP2D) has been identified.

Intervention: RP7214

Part II (dose expansion) RP7214 + Azacitidine

Participants will receive RP7214 orally at the MTD/RP2D in combination with Azacitidine in a 28-day cycle.

Intervention: RP7214

Outcomes

Primary Outcomes

Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of RP7214 in combination with azacitidine

Time Frame: 28 days

The maximum tolerated dose will be defined as the highest dose tested in which a DLT is experienced by 0 out of 3 or 1 out of 6 patients among the dose levels.