Clinical trial NCT05246384: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Myelodysplastic Syndromes
Chronic Myelomonocytic Leukemia
Acute Myeloid Leukemia
Keywords: RP7214
Dihydro-orotate Dehydrogenase (DHODH)
Lead sponsor: Rhizen Pharmaceuticals SA
Sponsor class: INDUSTRY
First posted: 2022-02-18
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: open-label, non-randomized, two-part Phase I/Ib study
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Patient must sign informed consent.
2. Patient should be ≥ 18 years of age.
3. 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.
4. Patient should have an Eastern Cooperative Oncology Group (ECOG) Performance score of 0 to 2.
5. Patients must be amenable to serial bone marrow biopsies/aspirates and peripheral blood sampling as required by the protocol.

Exclusion Criteria:

1. 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.
2. Patients with rapidly increasing peripheral blast counts (WBC count \> 25,000/μL) while on hydroxyurea prior to C1D1.
3. Patients with Acute Promyelocytic Leukemia (French American-British Class M3 AML).
4. 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.
5. Patient who discontinued prior therapy with DHODH inhibitors or azacitidine due to drug-related toxicity.
6. Evidence of uncontrolled/progressing infection.
7. Patients with immediate life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or Disseminated Intravascular Coagulation (DIC).
8. Presence of isolated extramedullary relapse.
9. Pregnant or lactating women

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of RP7214 in combination with azacitidine
timeFrame: 28 days
Secondary outcomes:
measure: Tmax
timeFrame: 35 days
measure: Objective Response Rate (ORR)
timeFrame: 2 years
measure: Clinical Benefit Rate (CBR)
timeFrame: 2 years
measure: Duration of Remission
timeFrame: 2 years
measure: Percentage of patients requiring blood and/or platelet transfusions
timeFrame: 2 years
measure: Cmax
timeFrame: 35 days
measure: AUC
timeFrame: 35 days
Other outcomes:
Locations:
Study officials:
References: