AML/MDSPhase 1NCT04139434
Dose-Escalation Study of Oral Administration of LP-108 as Monotherapy and in Combination With Azacitidine in Patients With Relapsed or Refractory MDS, CMML, or AML
A Phase 1 study testing LP-108 and LP-108 and azacitidine in people with AML/MDS and CMML, run by Newave Pharmaceutical Inc at 7 sites in 2 countries.
Trial summary
A Phase 1, Multicenter, Open-label, Dose-escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Clinical Activity of Orally Administered LP-108 as Monotherapy and in Combination with Azacitidine in Subjects with Relapsed or Refractory Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia… Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- LP-108 and LP-108 and azacitidine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 6 Jul 2020to 19 Dec 2025
- Phase
- Phase 1
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
- A subject will be eligible for study participation if the subject meets the following criteria:
- Eligible subject must have an advanced hematologic malignancy including:
- MDS with refractory anemia with excess blasts (RAEB; subtype RAEB-1 or RAEB-2) as defined by World Health Organization (WHO) 2016 revised criteria and/or MDS with high- or very high-risk (risk score > 4.5) per the Revised International Prognostic Scoring System (IPSS-R) (Greenberg et al. 2012) that is relapsed or refractory to prior therapy for MDS, or the subject is intolerant to established therapy known to provide clinical benefit for their condition in the opinion of the Investigator; Or relapsed and/or refractory MDS subjects in whom the Investigators feel would benefit from Arm 2.
- Relapsed and/or primary refractory AML as defined by WHO 2016 revised criteria; Or frontline older and/or unfit AML subjects in whom the Investigators feel would benefit from Arm 2.
- CMML (with ≥ 5% blasts in bone marrow) as defined by WHO 2016 revised criteria that is relapsed and/or refractory and that, in the opinion of the Investigator, requires treatment or that has exhausted treatment options that would be considered standard of care.
- Subject's prior therapies may include other BCL2 inhibitors and other HMA agents for Arm 2.
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- Blast count ≤ 30 × 10^9 cells/L at the time of initiating investigational therapy (hydroxyurea is allowed to control blast count prior to and during therapy).
- Subject must have adequate coagulation, renal, and hepatic function.
- Activated partial thromboplastin time and prothrombin time not to exceed 1.5 × the upper limit of normal (ULN);
- Calculated creatinine clearance (Cr Cl) ≥ 30 mL/min using 24-hour CrCl OR Cockcroft-Gault formula (using actual body weight)
- UK and EU only: Estimated glomerular filtration rate (GFR) ≥ 30 mL/min/1.73m2 using the modification of diet in renal disease (MDRD) equation.
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 ×ULN; bilirubin ≤ 1.5 × ULN (except subjects with Gilbert's Syndrome, who may have a bilirubin > 1.5 × ULN, per discussion between the Investigator and the Medical Monitor).
- Adequate cardiac function defined as: shortening fraction of ≥ 27% by echocardiogram, or ejection fraction of ≥ 50% by 2D echocardiogram without Doppler.
Who cannot join
- A subject will not be eligible for study participation if he/she meets any of the following criteria.
- Subjects with a diagnosis of promyelocytic leukemia/retinoic acid receptor alpha (PML-RARA) or non-PML-RARA rearranged acute promyelocytic leukemia (APL).
- Subjects who have undergone hematopoietic stem cell transplantation (HSCT) within 60 days of the first dose of LP-108, or subjects on immunosuppressive therapy post-HSCT at the time of Screening, or with clinically significant graft-versus-host disease (GVHD). (Subjects in relapse after allogeneic transplantation must be off calcineurin inhibitors for at least 4 weeks. The use of topical steroids and/or up to 20 mg/day prednisone or equivalent systemic steroids for ongoing GVHD is permitted).
- Subject has received any of the following therapies within 14 days or 5 half-lives (whichever is shorter) prior to the first dose of study drug, or has not recovered to ≤ Grade 1 clinically significant adverse effect(s) of the previous therapy:
- Any anti-cancer therapy including chemotherapy, hormonal therapy, biologic or immunotherapy, targeted small molecule agents, etc. (corticosteroid therapy < 20 mg/day prednisone equivalent for < 14 days at time of study treatment and hydroxyurea cytoreduction therapy according to institutional guidelines to treat disease associated symptoms are permitted).
- Any investigational therapy.
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- There is 28-day washout period required for subject who have had prior CAR-T treatment if there is no evidence of cytokine release syndrome (CRS) or other adverse events related to the CAR-T treatment per discussion with the Medical Monitor.
- Subject has received the following medications or therapies within 7 days or 5 half-lives (whichever is shorter) prior to the first dose of study drug:
- Cytochrome P450, family 3, subfamily A (CYP3A4) strong inhibitors (see Appendix 10 for strong CYP3A4 inhibitors). In Phase 1b of this trial, the criterion regarding CYP3A4 strong inhibitors will be removed at time of amendment of the trial when Phase 1b is to be initiated. The amendment will include recommendations on concomitant dosing of LP-108 and strong CYP3A4 inhibitors such as azole antifungal agents, PK monitoring for the initial weeks on study, as well as closer safety monitoring for subjects.
- Strong CYP3A4 inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort.
- Inhibitors of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) (see Appendix 11 for P gp and BCRP inhibitors).
- Immunosuppressive drugs (equivalent to >10mg prednisone) for underlying autoimmune or rheumatologic conditions.
- All statins as they could inhibit bilirubin uptake transporter OATP1B1 and OATP1B3 (the washout period should always be 5 half-lives) (see Appendix 11)
- Subject has baseline prolongation of the corrected QTc > 480 ms (calculated per Fridericia's formula [QTc = QT/RR (1/3)].
- Subject has a history of other malignancies other than the eligible hematologic malignancy within the past 1 year prior to study entry, with the exception of:
- Subject with breast cancer or prostrate cancer on endocrine therapy with stable disease.
- Adequately treated in situ carcinoma of the cervix uteri;
- Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
- Previous malignancy confined and surgically resected (or treated with other
- Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
- Uncontrolled systemic infection (bacterial, fungal, viral)
- Known active or poorly controlled human immunodeficiency virus or active hepatitis B or C infection
- Unexplained fever > 38.5 °C during the Screening period or on their first day of study drug administration (at the discretion of the Investigator, if the fever is considered related to the subject's malignancy may be enrolled).
- Subjects with known and active central nervous system (CNS) involvement (radiographic or cytologic) at Screening; subjects with history of CNS involvement who have no symptoms suggestive of CNS disease and have had at least 2 successful lumbar punctures without cytologic evidence of leukemia may be included after discussion and approval of the Medical Monitor. (Evaluation of cerebrospinal fluid is only required if there is a clinical suspicion of CNS involvement by leukemia during screening in subjects without a history of CNS involvement).
- Subjects with immediate life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.
- Requires ongoing treatment with
- Systemic acid-reducing agents including H-2-receptor antagonists and proton pump inhibitors
- Sensitive CYP2C8 substrates (such as montelukast, pioglitazone, repaglinide, rosiglitazone) or CYP2C8 substrates with a narrow therapeutic index (e.g., amiodarone, fosphenytoin, paclitaxel, penprocoumon, phenytoin)
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States4 sites
University of Michigan
Ann Arbor, Michigan, 48109
University of Cincinnati
Cincinnati, Ohio, 45221
Ohio State Comprehensive Cancer Center
Columbus, Ohio, 43210
MD Anderson Cancer Center
Huston, Texas, 77030
Spain3 sites
Institut Català d'oncologia - ICO Badalona
Badalona, Barcelona, 08916
Hospital San Pedro de Alcántara
Cáceres, Cáceres, 10003
Instituto de Investigación Sanitaria La Fe
Valencia, Valencia, CP 46026
About this study
Official title: A Phase 1, Multicenter, Open-label, Dose-escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Clinical Activity of Orally Administered LP-108 as Monotherapy and in Combination With Azacitidine in Subjects With Relapsed or Refractory Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), or Acute Myeloid Leukemia (AML)
A Phase 1, Multicenter, Open-label, Dose-escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Clinical Activity of Orally Administered LP-108 as Monotherapy and in Combination with Azacitidine in Subjects with Relapsed or Refractory Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), or Acute Myeloid Leukemia (AML)
Read the detailed description
The primary objectives are to assess the safety and tolerability profile, determine the maximum tolerated dose (MTD), and/or the recommended Phase 2 dose (RP2D) of LP-108 administered daily as a single agent dosed orally and in combination with azacitidine at 75 mg/m2 in adult subjects with relapsed/refractory MDS/CMML/AML; to characterize the pharmacokinetics (PK) profile of LP-108 as monotherapy and in combination with azacitidine in adult subjects with relapsed/refractory MDS/CMML/AML.
Secondary objectives are to evaluate preliminary efficacy regarding the effect of LP-108 (monotherapy or combination therapy) on ORR for AML, MDS, CMML, PFS, DOR, and OS
- Conditions
- AML/MDS, CMML, Relapse, Refractory Acute Lymphoblastic Leukemia, Relapse Leukemia, Relapsed Adult AML
- Being tested
- LP-108, LP-108 and azacitidine
- Keywords
- AML, MDS, CMML, relapse, refractory, LP-108
- Medical subject headings
- Recurrence, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LP-108Drug
For the dose escalation phase, LP-108 will be given once daily at the following dose levels: 100 mg QD, 200 mg QD, 400 mg QD, 600 mg QD, 800 mg QD, 1000 mg QD.
LP-108 and azacitidineDrug
For the dose escalation phase, LP-108 will be given once daily at the following dose levels: 100 mg QD, 200 mg QD, 400 mg QD, 600 mg QD, 800 mg QD, 1000 mg QD, with azacitidine at the standard dose of 75 mg/m2 on Day 1 - Day 7 of each 28-day cycle (weekly schedule) or on Days 1-5, 8, 9 of each 28-day cycle (5-2-2 schedule), according to institutional guidelines.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation Phase: LP-108 monotherapy | Experimental | Three to 6 subjects per treatment cohort will be assigned to receive sequentially higher oral doses of LP-108 on a once daily schedule for 28 days (a "Cycle") starting at a dose of 100 mg. Receives: Drug: LP-108 |
| Dose Expansion Phase: LP-108 in combination with azacitidine | Experimental | Three to 6 subjects per treatment cohort will be assigned to receive sequentially higher oral doses of LP-108 on a once daily schedule for 28 days (a "Cycle") starting at a dose of 100 mg in combination with azacitidine at 75 mg/m2. Receives: Drug: LP-108 and azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
Measured: up to 13 cycles (one cycle has 4 weeks)
Recommended Phase 2 dose (RP2D)
Measured: up to 13 cycles (one cycle has 4 weeks)
The pharmacokinetic (PK) profile of LP-108: Maximum Plasma Concentration [Cmax]
Measured: At Cycle 1 Day 1 (24 h PK), Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 22, Cycle 2 Day 1 (24 h PK)
The PK profile of LP-108: Area Under the Curve [AUC]
Measured: At Cycle 1 Day 1 (24 h PK), Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 22, Cycle 2 Day 1 (24 h PK)
The PK profile of LP-108: Time at Maximum Concentration [Tmax]
Measured: At Cycle 1 Day 1 (24 h PK), Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 22, Cycle 2 Day 1 (24 h PK)
Secondary outcomes (7)
Objective Response Rate (ORR) for AML
Assessment will be based on revised recommendations of the ELN 2017.
Measured: up to 13 cycles (one cycle has 4 weeks)
ORR for MDS
Assessment will be based on the proposed International Working Group 2006 criteria for MDS patients.
Measured: up to 13 cycles (one cycle has 4 weeks)
ORR for CMML
Assessment will be based on international consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) for CMML patients.
Measured: up to 13 cycles (one cycle has 4 weeks)
Progression-Free Survival (PFS)
PFS is defined as the time from start of treatment until objective disease progression or death, whichever occurs first.
Measured: up to 13 cycles (one cycle has 4 weeks)
Duration of Response (DOR)
DOR is for all subjects achieving an objective response.
Measured: up to 13 cycles (one cycle has 4 weeks)
Event-Free Survival (EFS)
EFS is defined as the time from the start of LP-108 therapy until the earliest date of refractory disease or relapse.
Measured: up to 13 cycles (one cycle has 4 weeks)
Overall Survival (OS)
Overall survival is defined as the time from treatment initiation until death from any cause.
Measured: up to 13 cycles (one cycle has 4 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2019
- Study start6 Jul 2020
- Primary completion19 Dec 2025
- Study completion19 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AML/MDSStudies 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- A classic "3+3" design will be used to establish dose-limiting toxicity (DLT), MTD, and RP2D.
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Newave Pharmaceutical Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04139434
- Sponsor's protocol ID
- LP-108P
- Status last verified
- Jan 2026
- First submitted
- 18 Oct 2019
- Last updated
- 23 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No