Study to Evaluate the Safety, Pharmacokinetics and Clinical Activity of RP7214 in Combination With Azacitidine in Patients With Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia and Acute Myeloid Leukemia

NCT05246384 | Withdrawn Phase 1

• 1 other identifier: RP7214-2102
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Acute Myeloid Leukemia

Keywords

RP7214; Dihydro-orotate Dehydrogenase (DHODH)

Outcome Measures

Primary Outcomes (1)

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

  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.

  28 days

Secondary Outcomes (7)

• Tmax

  35 days

• Objective Response Rate (ORR)

  2 years

• Clinical Benefit Rate (CBR)

  2 years

• Duration of Remission

  2 years

• Percentage of patients requiring blood and/or platelet transfusions

  2 years

Study Arms (2)

Part I (dose escalation) RP7214 + Azacitidine

EXPERIMENTAL

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.

Drug: RP7214

Part II (dose expansion) RP7214 + Azacitidine

EXPERIMENTAL

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

Drug: RP7214

Interventions

RP7214 DRUG

RP7214 will be administered daily twice a day orally; Azacitidine will be administered from Days 1 to 7 of each 28-day cycle

Part I (dose escalation) RP7214 + Azacitidine; Part II (dose expansion) RP7214 + Azacitidine

Eligibility Criteria

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

You may qualify if:

• 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 2.
• Patients must be amenable to serial bone marrow biopsies/aspirates and peripheral blood sampling as required by the protocol.

You may not qualify if:

• 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 C1D1. 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 C1D1.
• 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 C1D1.
• 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

Sponsors & Collaborators

• Rhizen Pharmaceuticals SA: lead

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic; Leukemia, Myeloid, Acute

Interventions

RP7214

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

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

Model Details: open-label, non-randomized, two-part Phase I/Ib study

Study Record Dates

• First Submitted: January 29, 2022
• First Posted: February 18, 2022
• Study Start: January 1, 2023
• Primary Completion: December 1, 2024
• Study Completion: November 1, 2025
• Last Updated: October 31, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share