Myelodysplastic SyndromesPhase 1/2NCT05246384
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
A Phase 1/2 study testing RP7214 in people with Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia, run by Rhizen Pharmaceuticals SA.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, Acute Myeloid Leukemia
- What is being tested?
- RP7214
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jan 2023to Nov 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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.
Who cannot join
- 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.
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- 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
About this study
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
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.
- Being tested
- RP7214
- Keywords
- RP7214, Dihydro-orotate Dehydrogenase (DHODH)
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RP7214Drug
RP7214 will be administered daily twice a day orally; Azacitidine will be administered from Days 1 to 7 of each 28-day cycle
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: RP7214 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 28 days
Secondary outcomes (7)
Tmax
Pharmacokinetics: Time to Reach Maximum Concentration (Tmax) of RP7214
Measured: 35 days
Objective Response Rate (ORR)
Defined as the percentage of patients who achieve Complete Remission (CR), Complete Remission with incomplete bone marrow recovery (CRi) and Partial Remission (PR)
Measured: 2 years
Clinical Benefit Rate (CBR)
Defined as the percentage of patients achieving a CR, CRi, PR and Stable Disease (SD) lasting for at least 8 weeks.
Measured: 2 years
Duration of Remission
Defined as the number of days from the date of first remission (CR, CRi, or PR) to the recurrence or Progressive Disease (PD)
Measured: 2 years
Percentage of patients requiring blood and/or platelet transfusions
Defined as number of patients requiring blood and/or platelet transfusions
Measured: 2 years
Cmax
Pharmacokinetics: Maximum Concentration (Cmax) of RP7214
Measured: 35 days
AUC
Pharmacokinetics: Area Under the Concentration Curve (AUC) of RP7214
Measured: 35 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2022
- Study startJan 2023 (estimated)
- Primary completionDec 2024 (estimated)
- Study completionNov 2025 (estimated)
Why it stopped: Change in development plan
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- open-label, non-randomized, two-part Phase I/Ib study
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rhizen Pharmaceuticals SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05246384
- Sponsor's protocol ID
- RP7214-2102
- Status last verified
- Oct 2022
- First submitted
- 29 Jan 2022
- Last updated
- 31 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05246384
- Acronym / sponsor ID
- RP7214-2102
- Keywords
- RP7214, Dihydro-orotate Dehydrogenase (DHODH)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Change in development plan
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Rhizen Pharmaceuticals SAIndustry (pharma, biotech, devices)
- Study start
- Jan 2023 (estimated)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Nov 2025 (estimated)
- First posted
- 18 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- open-label, non-randomized, two-part Phase I/Ib study
| Arm | Type | Receives |
|---|---|---|
| Part I (dose escalation) RP7214 + Azacitidine | Experimental | Drug: RP7214Participants 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. |
| Part II (dose expansion) RP7214 + Azacitidine | Experimental | Drug: RP7214Participants will receive RP7214 orally at the MTD/RP2D in combination with Azacitidine in a 28-day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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:
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RP7214RP7214 will be administered daily twice a day orally; Azacitidine will be administered from Days 1 to 7 of each 28-day cycle | Drug | Part I (dose escalation) RP7214 + Azacitidine, Part II (dose expansion) RP7214 + Azacitidine |
Primary outcome
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.
7 secondary outcomes
Tmax
Time frame: 35 days
Objective Response Rate (ORR)
Time frame: 2 years
Clinical Benefit Rate (CBR)
Time frame: 2 years
Duration of Remission
Time frame: 2 years
Percentage of patients requiring blood and/or platelet transfusions
Time frame: 2 years
Cmax
Time frame: 35 days
AUC
Time frame: 35 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing RP7214 in people with Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia, run by Rhizen Pharmaceuticals SA.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 31 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of RP7214 in combination with azacitidine (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2022.