Acute Myeloid Leukemia RefractoryPhase 1/2AML-NETNCT06150040
Acute Myeloid Leukemia Treated With With NETrin Abs in Combination With [AZACITIDINE + VENETOCLAX]
A Phase 1/2 study testing NP137, Azacitidine Injection and Venetoclax in people with Acute Myeloid Leukemia Refractory, run by Centre Leon Berard at 1 site in France.
Trial summary
The aim of this study is to investigate the safety and the clinical activities of NP137 when combined with Azacitidine and Venetoclax in patients with refractory acute myeloid leukemia after 2 cycles of Azacitidine and Venetoclax. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Acute Myeloid Leukemia Refractory
- What is being tested?
- NP137, Azacitidine Injection and Venetoclax
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteFrance
- Study dates
- 11 Sep 2024to 18 Feb 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 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- I1. Adult is ≥ 65 years of age at the time of signing the ICF (Inform Consent Form)
- I2. Histologically confirmed acute myeloid leukemia (AML) as defined by the 2022 World Health Organization (WHO) Classification.
- I3. Patient previously untreated for AML (except with the first 2 cycles of his/her current A+V treatment) and who is considered as ineligible for induction regimen and intensive chemotherapy due to age and other comorbidity that the physician judges to be incompatible with such treatment:
- OR Patient with expected poor prognosis under intensive /induction chemotherapy (e.g. with complex karyotype) OR "No-go" patients according ALFA decision tool ([e.i: patient with Adverse cytogenetics ≥1 of the following: mKRAS, mTP53)
- Note : Patients with favourable-risk cytogenetics with intensive chemotherapy are not eligible, such as:
- t(8;21)(q22;q22.1); RUNX1-RUNX1T1
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- inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11
- Mutated NPM1 without FLT3-ITD or with FLT3-ITDlow†
- Biallelic mutated CEBPA
- I4. Patients under treatment by A+V treatment as standard first line treatment for AML with no CR nor CRi after 2 cycles of AZACITIDINE +VENETOCLAX.
- I5. Patient must be, in the judgment of the investigator, an appropriate candidate for an experimental therapy i.e. with no available other standard treatment or options except palliative care.
- I6. Participant must have a life expectancy of at least 12 weeks.
- I7. Participants has with Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 are eligible to the safety run-in part whatever their age. Then for the expansion part, patient with ECOG PS (Performance Status) of 0 to 2 for subject ≥ 75 years OR of 0 to 3 for subject ≥ 65 to 74 years of age are eligible.
- I8. Demonstrate adequate cardiac function:
- QTc (corrected QT interval) ≤470ms
- Resting systolic BP <160mmHg
- Resting diastolic BP <100mmHg
- LVEF (left ventricular ejection fraction) ≥50% as determined by multiple-gated acquisition (MUGA) scan or transthoracic echocardiogram.
- I9. Demonstrate adequate organ function as defined in table below, all screening laboratory tests should be performed within 7 days prior Cycle 1 day 1 :
- White Blood Cells Count < 25 × 109/L or lower; use of leukapheresis or hydroxyurea is permitted to achieve this concentration before Cycle 1 Day 1, at the discretion of the treating physician and according to institutional practice. (see exclusion criteria E6)
- Creatinine clearance Calculated creatinine clearance ≥30 mL/min determined by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula OR via urine collection for 24-hour creatinine clearance or serum creatinine ≤ 2 upper limit of normal (ULN)
- Bilirubin Total bilirubin < 2 × the upper limit of normal (ULN) If total bilirubin ≥ 2 ULN, Direct Bilirubin must be < 2 x ULN unless considered due to leukemic organ involvement(< 5 ULN) and with the following Exception: Patients with known Gilbert disease who have serum bilirubin level ≤ 3 ULN may be enrolled.
- SGOT (serum glutamate oxaloacetate transaminase) (AST) and SGPT (serum glutamate pyruvate transaminase) (ALT) ≤ 3 x ULN unless considered due to leukemic organ involvement (< 5 ULN)
- I10. Patient has no evidence of spontaneous tumor lysis syndrome (TLS) before NP137 introduction.
- I11. Female subjects must be either:
- Postmenopausal; defined no menses for ≥ 12 months without an alternative medical cause; OR
- Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
- I12. Non-sterile male subjects must use contraceptive methods with partner(s) prior to beginning study drug administration and continuing up to 3.5 months [106 days] after the last dose of NP137. Male subjects must agree to refrain from sperm donation from initial study drug administration during this same period.
- I13. Patient must understand, sign, and date the written voluntary informed consent form prior to any protocol-specific procedures.
- I14. Patient must be able and willing to comply with study visits and procedures as per protocol.
- I15. Patients must be covered by a medical insurance
Who cannot join
- E1. Patient who is eligible for any curative therapy including but not limited to induction / intensive chemotherapies, CAR-T cell therapy and agrees to receive this therapy.
- E2. Patient previously treated for AML with a hypomethylating agent and/or other chemotherapeutic agents either conventional or experimental for AML before NP137 introduction.
- E3. Patient who has acute promyelocytic leukemia.
- E4. Patient who experienced:
- Any persisting non hematological grade ≥ 3 AZACITIDINE AND VENETOCLAX related Adverse events before C1D1.
- Any vascular disorder grade ≥ 3 within 6 months prior C1D1.
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- E5. History of severe allergic anaphylactic reactions (≥ grade 3) to one of the components of the study drugs or to humanized antibodies or premedication and/or any of their excipients.
- E6. Prior therapy or needs to be treated with a forbidden concomitant/concurrent therapies/procedures including:
- Any investigational agent or have used an investigational device.
- Major surgery within 4 weeks of start of study treatment. Participants must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment, C1D1.
- Anti-cancer treatment other than those specified in the protocol i.e. AZACITIDINE + VENETOCLAX.
- Live or live-attenuated vaccine within 30 days prior to the first dose of study treatments. Note: Inactivated vaccine are allowed.
- Note:
- During the safety run in phase, Hydroxyurea is authorized prior C1D1 but a wash-out period of 2 days or 5*t1/2 before C1D1 whatever • shorter is required.
- During the expansion phase, the use of hydroxyurea for patients with rapidly proliferative disease is allowed during the course of cycle 1 at the discretion of the treating physician and according to institutional practice
- E7. Active or untreated central nervous system involvement.
- E8. Other invasive malignancy in the last 2 years except for those with a minimal risk of metastasis or death such as adequately managed in-situ carcinoma of the cervix, basal or squamous cell skin cancer, localized prostate cancer or ductal carcinoma in situ treated with curative intent, previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
- E9. Patients with any other known concurrent severe and/or uncontrolled medical condition including but not limited to diabetes, cardiovascular disease including hypertension, renal disease, or active uncontrolled infection, which could compromise participation in the study. For active infection requiring systemic therapy or fever likely secondary to infection within prior 48 hours: prophylactic antibiotics or prolonged course of IV antibiotics for controlled infection are allowed.
- E10. Patients with uncontrolled hypertension despite adequate medical therapy, active and uncontrolled congestive heart failure New York Heart Association (NYHA) class III/IV, clinically significant and uncontrolled arrhythmia as judged by the treating physician.
- E11. Patient with evidence of uncontrolled active infection requiring systemic therapy (viral, bacterial or fungal).
- E12. Patients known to be positive to HIV (testing will be performed a screening).
- E13. Patients known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load within 3 months. Hepatitis B or C testing is not required and subjects with serologic evidence of prior vaccination to Hepatitis B virus (i.e., HBs Ag, anti-HBs+ and anti-HBc-) may participate.
- Patients placed under a legal protection regimen: Judicial Safeguards, curatorship or guardianship.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I/II Study to Evaluate the Safety Clinical and Biological Activity of a Humanized Monoclonal Antibody Targeting Netrin-1 (NP137) in Combination With Standard AZACITIDINE+ VENETOCLAX in Patients With Refractory Acute Myeloid Leukemia
The aim of this study is to investigate the safety and the clinical activities of NP137 when combined with Azacitidine and Venetoclax in patients with refractory acute myeloid leukemia after 2 cycles of Azacitidine and Venetoclax.
Read the detailed description
The dual treatment, VENETOCLAX and AZACITIDINE, is the standard of care for patients with newly diagnosed AML who are ineligible for intensive chemotherapy. However, upfront resistance as well as relapse following initial response demonstrate the need to improve this therapeutic strategy.
NP137 is a first-in-class humanized monoclonal antibody targeting specifically and selectively Netrin-1. Based on data collected from non clinical studies NP137 should act in synergy with VENETOCLAX and AZACITIDINE to reactivate and enhance the apoptotic pathway in AML cells.
The herein proposed study to assess the safety (Safety run in/ phase I part) and the preliminary efficacy signal (extension phase II part) of the NP137 when combined to AZACITIDINE AND VENETOCLAX in patients with refractory acute myeloid leukemia after 2 cycles of Azacitidine and Venetoclax.
This study will be an open-label, Phase I/II trial. the first part, consists to a safety run to assess the security and the tolerability of the drugs combination from the first 6 to 12 first patients enrolled into the study. All patients will receive a fixed dose of NP137 at the RP2D (Recommended Phase 2 Dose) determined from the First in human NP137 study(DL1) . A dose deescalation of NP137 is planned to DL-1 according to the Dose Limiting Toxicities observed during this period. The second part will be will be then conducted as a phase II using an adaptive Bayesian approach allowing to quickly stop treatment without evidence of efficacy. The clinical activity will be assessed based on ELN (European LeukemiaNet) criteria 2027 for the Acute Myeloid Leukemia.
- Conditions
- Acute Myeloid Leukemia Refractory
- Being tested
- NP137, Azacitidine Injection, Venetoclax
- Keywords
- Acute Myeloid Leukemia, Unfit to intensive chemotherapy, NP137, Netrin-1, monoclonal antibody, Azacitidine and Venetoclax, Refractory to azacitidine and venetoclax
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NP137Drug
IV infusion, 14mg/kg or 9mg/kg, every 2 weeks
Azacitidine InjectionDrug
Subcutaneous injection, 75 mg/m², on cycle Days 1-7 (28-days cycle)
VenetoclaxDrug
Orally, 70 mg, every day on Days 1-28
| Study group | Role | What they receive |
|---|---|---|
| Refractory Acute Myeloid Leukemia | Experimental | Patients who meet primary refractory disease definition according to ELN criteria after 2 cycles of standard [AZACITIDINE +VENETOCLAX] (i.e: patients who have failed to have a complete remission (with complete (CR) or incomplete hematologic recovery (CRi)) Receives: Drug: NP137; Drug: Azacitidine Injection; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety run in part : Incidence of Dose Limiting Toxicities (DLT)
To assess the safety of the proposed therapeutic combination [NP137 + AZACITIDINE VENETOCLAX] according to the incidence of Dose Limiting Toxicities (DLT) as defined per protocol.
Measured: 4 weeks
Phase II part : Objective Response Rate (ORR)
To investigate the clinical activity of the proposed therapeutic combination [NP137 + AZACITIDINE + VENETOCLAX] through the Objective Response Rate (ORR) over the 4 cycles of AZACITIDNE +VENETOCLAX+ NP137 administration.
ORR will be defined as the proportion of patients with a complete remission (CR) or complete remission with incomplete hematologic recovery (CRi), as best overall response over the 4 cycles of the study combination.
Measured: 16 weeks
Secondary outcomes (15)
Adverse events
Incidence of any adverse events graded according to NCI-CTCAE V5.0
Measured: from the date of first intake of study drug until to 90 days after study drug discontinuation, (at least up to 12 months for the last patient in)
Duration of response
Measurement of the duration of response (CR/CRi)
Measured: from the time of first documented response until the first progression or death, (at least up to 12 months for the last patient in)
Best overall response (BOR)
Best overall response, is determined by the best response designation. For subjects without documented progression or subsequent anticancer therapy, all available response designations will contribute to the BOR determination :from the date of first intake of study drug until progression or at time of initiation of a new anti-cancer treatment
Measured: Every 28 days, up to 1 year
Objective Response Rate
Objective Response Rate after 2 cycles of study treatment defined as the proportion of participants who achieve: complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) after 2 cycles of treatment (2 cycles of A+V including 4 injections of NP137)
Measured: 8 weeks
Overall survival
Overall survival measured from the date of treatment start to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive.
Measured: Until up to 1 year follow-up of the last patient enrolled
Progression Free survival
Progression Free survival defined as the time from the initiation of the study treatment until first evidence of disease treatment failure : from the date of first intake of study drug until progression
Measured: Every 28 days, up to 1 year follow-up of the last patient enrolled
Treatment Failure
Time to Treatment Failure Rate (TTF) defined as the time from the initiation of study treatment to its early discontinuation. Reasons for prematurely discontinuing treatment can include cancer progression but also adverse events, patient choice, or death.
Measured: Continuously, up to 1 year follow-up of the last patient enrolled
Death in Medullary Aplasia
Death in Medullary Aplasia Rate based on cytological assessment: Deaths occurring ≥7 days following completion of initial treatment while cytopenic, with an aplastic or hypoplastic bone marrow obtained within 7 days of death, without evidence of persistent leukemia.
Measured: Every 28 days, up to 1 year follow-up of the last patient enrolled
Neutrophil / platelet count recovery
Time to neutrophil / platelet count recovery (absolute neutrophil count (ANC) > 1 × 109/L (defined as neutrophil recovery) and platelet count > 100 × 109/L (defined as platelet recovery)).
Measured: Continuously, up to 1 year follow-up of the last patient enrolled
Pharmacokinetic parameter: Cmax
Plasma peak concentration
Measured: Cycle 1 day 1, pre-dose; cycle 1 day 1, 3hours post-dose; cycle 1 day 2; cycle 1 day 7 or day 8; cycle 1 day 15, pre-dose; cycle 7 day 1, pre-dose; if Grade ≥3 infusion-related reaction and at the end of treatment visit (each cycle is 28 days)
Pharmacokinetic parameter: tmax
Time to reach the peak concentration
Measured: Cycle 1 day 1, pre-dose; cycle 1 day 1, 3hours post-dose; cycle 1 day 2; cycle 1 day 7 or day 8; cycle 1 day 15, pre-dose; cycle 7 day 1, pre-dose; if Grade ≥3 infusion-related reaction and at the end of treatment visit (each cycle is 28 days)
Pharmacokinetic parameter: AUCt (Area under the concentration-time)
Area under the concentration-time curve from time zero to the last sample with the quantifiable concentration
Measured: Cycle 1 day 1, pre-dose; cycle 1 day 1, 3hours post-dose; cycle 1 day 2; cycle 1 day 7 or day 8; cycle 1 day 15, pre-dose; cycle 7 day 1, pre-dose; if Grade ≥3 infusion-related reaction and at the end of treatment visit (each cycle is 28 days)
Pharmacokinetic parameter: AUC∞ (Area under the concentration-time)
Area under the concentration-time curve from time zero to infinity corresponding to the definite integral of a curve that describes the variation of a drug concentration in blood plasma as a function of time (drug exposure in plasma)
Measured: Cycle 1 day 1, pre-dose; cycle 1 day 1, 3hours post-dose; cycle 1 day 2; cycle 1 day 7 or day 8; cycle 1 day 15, pre-dose; cycle 7 day 1, pre-dose; if Grade ≥3 infusion-related reaction and at the end of treatment visit (each cycle is 28 days)
Pharmacokinetic parameter: CL (Clearance)
Clearance: volume of plasma from which NP137 is completely removed per unit time.
Measured: Cycle 1 day 1, pre-dose; cycle 1 day 1, 3hours post-dose; cycle 1 day 2; cycle 1 day 7 or day 8; cycle 1 day 15, pre-dose; cycle 7 day 1, pre-dose; if Grade ≥3 infusion-related reaction and at the end of treatment visit (each cycle is 28 days)
Pharmacokinetic parameter: t1/2
Terminal elimination half-life: time required for the amount of NP137 in the body to decrease by half.
Measured: Cycle 1 day 1, pre-dose; cycle 1 day 1, 3hours post-dose; cycle 1 day 2; cycle 1 day 7 or day 8; cycle 1 day 15, pre-dose; cycle 7 day 1, pre-dose; if Grade ≥3 infusion-related reaction and at the end of treatment visit (each cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2023
- Study start11 Sep 2024
- Primary completion18 Feb 2025
- Study completion18 Feb 2025
Why it stopped: low recruitment rate
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid Leukemia RefractoryStudies of the same condition, open and under way.
- More trials run by Centre Leon BerardThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Model description
- The therapeutic combinations NP137 + \[AZACITIDINE+VENETOCLAX\] will be administered on the first 6 patients enrolled in the study at Dose Level (14 mg/kg). According to safety rules based on the dose limiting toxicities occurence, a dose reduction of NP137 at Dose Level -1 (9 mg/kg) will be assessed in 6 additional patients. After the safety run in part, study will be opened with 35 patients (including patients from the safety run in) at DL or DL-1.
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Leon Berard
- Sponsor type
- University, hospital or other
- Collaborators
- NETRIS Pharma
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06150040
- Sponsor's protocol ID
- ET23-026
- Other IDs
- EU number
- Acronym
- AML-NET
- Status last verified
- Feb 2025
- First submitted
- 10 Nov 2023
- Last updated
- 20 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study to Evaluate the Safety Clinical and Biological Activity of a Humanized Monoclonal Antibody Targeting Netrin-1 (NP137) in Combination With Standard AZACITIDINE+ VENETOCLAX in Patients With Refractory Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT06150040
- Acronym / sponsor ID
- AML-NET / ET23-026
- Conditions
- Acute Myeloid Leukemia Refractory
- Keywords
- Acute Myeloid Leukemia, Unfit to intensive chemotherapy, NP137, Netrin-1, monoclonal antibody, Azacitidine and Venetoclax, Refractory to azacitidine and venetoclax
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: low recruitment rate
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Centre Leon BerardUniversity, hospital or other
- Collaborators
- NETRIS Pharma
- Study start
- 11 Sep 2024 (actual)
- Primary completion
- 18 Feb 2025 (actual)
- Study completion
- 18 Feb 2025 (actual)
- First posted
- 29 Nov 2023 (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.
The aim of this study is to investigate the safety and the clinical activities of NP137 when combined with Azacitidine and Venetoclax in patients with refractory acute myeloid leukemia after 2 cycles of Azacitidine and Venetoclax.
Detailed description
The dual treatment, VENETOCLAX and AZACITIDINE, is the standard of care for patients with newly diagnosed AML who are ineligible for intensive chemotherapy. However, upfront resistance as well as relapse following initial response demonstrate the need to improve this therapeutic strategy.
NP137 is a first-in-class humanized monoclonal antibody targeting specifically and selectively Netrin-1. Based on data collected from non clinical studies NP137 should act in synergy with VENETOCLAX and AZACITIDINE to reactivate and enhance the apoptotic pathway in AML cells.
The herein proposed study to assess the safety (Safety run in/ phase I part) and the preliminary efficacy signal (extension phase II part) of the NP137 when combined to AZACITIDINE AND VENETOCLAX in patients with refractory acute myeloid leukemia after 2 cycles of Azacitidine and Venetoclax.
This study will be an open-label, Phase I/II trial. the first part, consists to a safety run to assess the security and the tolerability of the drugs combination from the first 6 to 12 first patients enrolled into the study. All patients will receive a fixed dose of NP137 at the RP2D (Recommended Phase 2 Dose) determined from the First in human NP137 study(DL1) . A dose deescalation of NP137 is planned to DL-1 according to the Dose Limiting Toxicities observed during this period. The second part will be will be then conducted as a phase II using an adaptive Bayesian approach allowing to quickly stop treatment without evidence of efficacy. The clinical activity will be assessed based on ELN (European LeukemiaNet) criteria 2027 for the Acute Myeloid Leukemia.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The therapeutic combinations NP137 + [AZACITIDINE+VENETOCLAX] will be administered on the first 6 patients enrolled in the study at Dose Level (14 mg/kg). According to safety rules based on the dose limiting toxicities occurence, a dose reduction of NP137 at Dose Level -1 (9 mg/kg) will be assessed in 6 additional patients. After the safety run in part, study will be opened with 35 patients (including patients from the safety run in) at DL or DL-1.
| Arm | Type | Receives |
|---|---|---|
| Refractory Acute Myeloid Leukemia | Experimental | Drug: NP137, Drug: Azacitidine Injection, Drug: VenetoclaxPatients who meet primary refractory disease definition according to ELN criteria after 2 cycles of standard [AZACITIDINE +VENETOCLAX] (i.e: patients who have failed to have a complete remission (with complete (CR) or incomplete hematologic recovery (CRi)) |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (31 listed)
- I1. Adult is ≥ 65 years of age at the time of signing the ICF (Inform Consent Form)
- I2. Histologically confirmed acute myeloid leukemia (AML) as defined by the 2022 World Health Organization (WHO) Classification.
- I3. Patient previously untreated for AML (except with the first 2 cycles of his/her current A+V treatment) and who is considered as ineligible for induction regimen and intensive chemotherapy due to age and other comorbidity that the physician judges to be incompatible with such treatment:
- OR Patient with expected poor prognosis under intensive /induction chemotherapy (e.g. with complex karyotype) OR "No-go" patients according ALFA decision tool ([e.i: patient with Adverse cytogenetics ≥1 of the following: mKRAS, mTP53)
- Note : Patients with favourable-risk cytogenetics with intensive chemotherapy are not eligible, such as:
Key exclusion criteria (23 listed)
- E1. Patient who is eligible for any curative therapy including but not limited to induction / intensive chemotherapies, CAR-T cell therapy and agrees to receive this therapy.
- E2. Patient previously treated for AML with a hypomethylating agent and/or other chemotherapeutic agents either conventional or experimental for AML before NP137 introduction.
- E3. Patient who has acute promyelocytic leukemia.
- Any persisting non hematological grade ≥ 3 AZACITIDINE AND VENETOCLAX related Adverse events before C1D1.
- Any vascular disorder grade ≥ 3 within 6 months prior C1D1.
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 |
|---|---|---|
| NP137IV infusion, 14mg/kg or 9mg/kg, every 2 weeks | Drug | Refractory Acute Myeloid Leukemia |
| Azacitidine InjectionSubcutaneous injection, 75 mg/m², on cycle Days 1-7 (28-days cycle) | Drug | Refractory Acute Myeloid Leukemia |
| VenetoclaxOrally, 70 mg, every day on Days 1-28 | Drug | Refractory Acute Myeloid Leukemia |
Primary outcome
Safety run in part : Incidence of Dose Limiting Toxicities (DLT)
Time frame: 4 weeks
To assess the safety of the proposed therapeutic combination [NP137 + AZACITIDINE VENETOCLAX] according to the incidence of Dose Limiting Toxicities (DLT) as defined per protocol.
Phase II part : Objective Response Rate (ORR)
Time frame: 16 weeks
To investigate the clinical activity of the proposed therapeutic combination [NP137 + AZACITIDINE + VENETOCLAX] through the Objective Response Rate (ORR) over the 4 cycles of AZACITIDNE +VENETOCLAX+ NP137 administration. ORR will be defined as the proportion of patients with a complete remission (CR) or complete remission with incomplete hematologic recovery (CRi), as best overall response over the 4 cycles of the study combination.
15 secondary outcomes
Adverse events
Time frame: from the date of first intake of study drug until to 90 days after study drug discontinuation, (at least up to 12 months for the last patient in)
Duration of response
Time frame: from the time of first documented response until the first progression or death, (at least up to 12 months for the last patient in)
Best overall response (BOR)
Time frame: Every 28 days, up to 1 year
Objective Response Rate
Time frame: 8 weeks
Overall survival
Time frame: Until up to 1 year follow-up of the last patient enrolled
Progression Free survival
Time frame: Every 28 days, up to 1 year follow-up of the last patient enrolled
Treatment Failure
Time frame: Continuously, up to 1 year follow-up of the last patient enrolled
Death in Medullary Aplasia
Time frame: Every 28 days, up to 1 year follow-up of the last patient enrolled
Neutrophil / platelet count recovery
Time frame: Continuously, up to 1 year follow-up of the last patient enrolled
Pharmacokinetic parameter: Cmax
Time frame: Cycle 1 day 1, pre-dose; cycle 1 day 1, 3hours post-dose; cycle 1 day 2; cycle 1 day 7 or day 8; cycle 1 day 15, pre-dose; cycle 7 day 1, pre-dose; if Grade ≥3 infusion-related reaction and at the end of treatment visit (each cycle is 28 days)
Pharmacokinetic parameter: tmax
Time frame: Cycle 1 day 1, pre-dose; cycle 1 day 1, 3hours post-dose; cycle 1 day 2; cycle 1 day 7 or day 8; cycle 1 day 15, pre-dose; cycle 7 day 1, pre-dose; if Grade ≥3 infusion-related reaction and at the end of treatment visit (each cycle is 28 days)
Pharmacokinetic parameter: AUCt (Area under the concentration-time)
Time frame: Cycle 1 day 1, pre-dose; cycle 1 day 1, 3hours post-dose; cycle 1 day 2; cycle 1 day 7 or day 8; cycle 1 day 15, pre-dose; cycle 7 day 1, pre-dose; if Grade ≥3 infusion-related reaction and at the end of treatment visit (each cycle is 28 days)
Pharmacokinetic parameter: AUC∞ (Area under the concentration-time)
Time frame: Cycle 1 day 1, pre-dose; cycle 1 day 1, 3hours post-dose; cycle 1 day 2; cycle 1 day 7 or day 8; cycle 1 day 15, pre-dose; cycle 7 day 1, pre-dose; if Grade ≥3 infusion-related reaction and at the end of treatment visit (each cycle is 28 days)
Pharmacokinetic parameter: CL (Clearance)
Time frame: Cycle 1 day 1, pre-dose; cycle 1 day 1, 3hours post-dose; cycle 1 day 2; cycle 1 day 7 or day 8; cycle 1 day 15, pre-dose; cycle 7 day 1, pre-dose; if Grade ≥3 infusion-related reaction and at the end of treatment visit (each cycle is 28 days)
Pharmacokinetic parameter: t1/2
Time frame: Cycle 1 day 1, pre-dose; cycle 1 day 1, 3hours post-dose; cycle 1 day 2; cycle 1 day 7 or day 8; cycle 1 day 15, pre-dose; cycle 7 day 1, pre-dose; if Grade ≥3 infusion-related reaction and at the end of treatment visit (each cycle is 28 days)
Results and safety
The study was stopped early (reason given: low recruitment rate). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2025.
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RecruitingPhase 1
First-in-human (FIH) Trial of GEN3018 in Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) or Higher-risk Myelodysplastic Syndrome (HR-MDS)
R/R AML, R/R HR-MDS
RecruitingPhase 2
Olutasidenib in Relapsed IDH1 Mutated AML Patients Who Have Previously Received Venetoclax
IDH1 Mutation, Relapsed / Refractory AML
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing NP137, Azacitidine Injection and Venetoclax in people with Acute Myeloid Leukemia Refractory, run by Centre Leon Berard at 1 site in France.
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 31 inclusion and 23 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: stopped early, as of the sponsor's last update on 20 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
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 stopped early (reason given: low recruitment rate). Results are not available in the source record.
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?
Safety run in part : Incidence of Dose Limiting Toxicities (DLT) (time frame: 4 weeks). The study lists 2 primary outcomes in all. 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 20 Feb 2025.