A Study of HMPL-306 in Advanced Hematological Malignancies With mIDH
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04764474|
Recruitment Status : Recruiting
First Posted : February 21, 2021
Last Update Posted : May 8, 2023
- Study Details
- Tabular View
- No Results Posted
- How to Read a Study Record
|Condition or disease||Intervention/treatment||Phase|
|Isocitrate Dehydrogenase Gene Mutation||Drug: HMPL-306||Phase 1|
HMPL-306 is a dual IDH1/2 inhibitor
This is a phase 1, open-label, multicenter, single-arm study to evaluate safety, tolerability, PK, PD, and preliminary efficacy of HMPL-306 administered orally in treatment of subjects with advanced relapsed, refractory, or resistant hematological malignancies that harbor IDH mutations (or co-mutations).
The study consists of 2 parts: a dose-escalation part (Part 1) and a dose-expansion part (Part 2). The dose-escalation part will determine the MTD/R2PD. The dose-expansion part will administer the MTD/RP2D to subjects with mIDH-positive hematological malignancies including, but not limited to AML, HR-MDS, AITL.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||75 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1, Open-Label, Multicenter Study of HMPL-306 in Advanced Hematological Malignancies With Isocitrate Dehydrogenase (IDH) Mutations|
|Actual Study Start Date :||February 28, 2021|
|Estimated Primary Completion Date :||September 30, 2023|
|Estimated Study Completion Date :||September 30, 2023|
All patients will be administered HMPL-306 orally QD
Administered orally QD in a 28-day continuous dosing treatment cycle
- Part 1: Number of Subjects with Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 28 days after first dose of study drug ]DLT is defined as an adverse event (AE) that meets protocol defined DLT criteria during cycle 1 and is at least possibly related to study drug.
- Part 1 and Part 2: Frequency and severity of AEs [ Time Frame: From the first dose of the study drug to 37 days after the last dose of study drug ]
- Number of Subjects with best overall response [ Time Frame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months ]Subjects with AML will be evaluated according to the 2017 ELN criteria Subjects with HR-MDS subjects will be evaluated according to the International Working Group response criteria in myelodysplasia Subjects with AITL will be evaluated according to the Lugano Classification for Hodgkin and Non-Hodgkin's Lymphoma Subjects with AML will be evaluated according to the 2017 ELN criteria Subjects with HR-MDS subjects will be evaluated according to the International Working Group response criteria in myelodysplasia Subjects with AITL will be evaluated according to the Lugano Classification for Hodgkin and Non-Hodgkin's Lymphoma Subjects with AML will be evaluated according to the 2017 ELN Criteria. Subjects with HR-MDS subjects will be evaluated according to the International Working Group response criteria in myelodysplasia Subjects with AITL will be evaluated according to the Lugano Classification for Hodgkin and Non-Hodgkin's Lymphoma
- Objective Response rate (ORR) [ Time Frame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months ]It is defined to include subjects who have the objective response.
- Clinical Benefit Rate (CBR) [ Time Frame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months ]CBR is defined as the proportion of subjects achieving objective response or SD.
- Overall survival (OS) [ Time Frame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months ]OS is defined as the time from the start of the study drug until death from any cause.
- Progression-free survival (PFS) [ Time Frame: From first dose of study drug to earlier of progression or death, assessed up to 36 months ]PFS is defined as the time from the start of study treatment to disease progression, or death due to any cause, whichever occurs first.
- Subjects with baseline transfusion dependence [ Time Frame: From the first dose of study drug to last dose of study drug, assessed up to 36 months ]It is defined as requiring transfusions of red blood cells (RBCs) or platelets within 56 days prior to the first dose of treatment.
- Subjects with post-baseline transfusion independence [ Time Frame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months ]It is defined as no RBC or platelet transfusion for at least ≥4 weeks (and separately ≥8 weeks) during treatment period.
- Maximum serum drug concentration [ Time Frame: PK weeks at screening through end of treatment, assessed up to 36 months ]Blood samples will be obtained from all patients for determination of the maximum serum concentration of HMPL-306.
- Time to maximum concentration [ Time Frame: PK weeks at screening through end of treatment, assessed up to 36 months ]Blood samples will be obtained from all patients for determination time to maximum concentration of HMPL-306.
- Area under the concentration-time curve (AUC) [ Time Frame: PK weeks at screening through safety follow-up, assessed up to 36 months ]Blood samples will be obtained from all patients for determination of the AUC of HMPL-306
- Concentration of 2-HG in plasma and/or bone marrow [ Time Frame: PK weeks at screening through safety follow-up, assessed up to 36 months ]Blood or bone marrow sample to determine the concentration of 2-HG
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
Key Inclusion Criteria:
Subjects may be enrolled in this study only if they satisfy all the following criteria (NOTE: This is not an exhaustive list):
- Subjects aged ≥18 years.
- ECOG performance status ≤ 2
- Subjects with advanced relapsed, refractory, or resistant hematological malignancies, as defined below:
- Subjects with documented IDH mutation per local or institutional next generation sequence (NGS).
- Subjects must be refractory to or intolerant of established therapies.
- Subjects who have received prior IDH inhibitor treatment may be enrolled in the escalation phase.
- Subjects with documented IDH mutation of any of these subsets: IDH1 (R132C), IDH1 (R132H), IDH (R140Q), and IDH2 (R172K), including co-mutations and any combination thereof per local and institutional NGS.
- Patients must have received at least 1 prior line of therapy. An established standard of care with proven benefit for which the patient is eligible, must not be available at the time of enrollment.
- Subjects with MDS must have a Revised International Prognostic Scoring System (IPSS-R) score of >4.5 (high and very high risk).
Patients with AML must not have standard therapeutic options available (including IDH inhibitors where approved) and have the following:
i. Relapsed AML unsuitable for intensive chemotherapy or venetoclax-based regimen or target agents; ii. Primary refractory AML unsuitable for intensive chemotherapy or venetoclax-based regimen or target agents.
Patients with relapsed/refractory AML/HR-MDS/AITL include the following:
i. Subjects who relapse after transplantation; ii. Subjects in second or later relapse; iii. Subjects who are refractory to initial induction or re-induction treatment.
- Subjects must not have progressed on prior IDH treatment unless isoform switching of the IDH mutation has been documented following progression on the prior IDH inhibitor.
Key Exclusion Criteria:
Subjects are not eligible for enrollment into this study if they meet any of the following criteria (NOTE: This is not an exhaustive list):
- Subjects who received an investigational agent <14 days prior to their first day of study drug administration.
- Subjects who are pregnant or breastfeeding.
- Subjects with an active severe infection, some treated infections and with an expected or with an unexplained fever >38.3°C during screening visits or on their first day of study drug administration.
- Subjects with some current or prior heart conditions.
- Subjects taking medications that are known to prolong the QT interval may not be eligible.
- Subjects with immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.
- Some subjects with some current or prior gastrointestinal or liver diseases.
- Subjects with inadequate organ function as defined by the protocol.
- Subjects with a medical condition, physical examination finding, or clinical laboratory finding that, in the Investigators opinion, contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the subject at high risk from treatment complications.
- Subjects with a known hypersensitivity to HMPL-306 or to any of its excipients.
- Subjects with presence of second primary malignant tumors within the last 2 years, with the exception of the following, if medically controlled: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, and carcinoma in situ of the breast.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04764474
|Contact: Alisha Khullar, MS,MBA||+1 973 287 firstname.lastname@example.org|
|Contact: Martin Benes, PhDemail@example.com|
|United States, California|
|University of California Irvine Medical Center||Recruiting|
|Orange, California, United States, 92868|
|Contact: Deepa Jeyakumar, MD firstname.lastname@example.org|
|United States, Georgia|
|Atlanta, Georgia, United States, 30322|
|Contact: Shannon Gleason 404-727-6123 email@example.com|
|Principal Investigator: William Blum, MD|
|United States, Massachusetts|
|University of Massachusetts Medical School||Recruiting|
|Worcester, Massachusetts, United States, 01655|
|Contact: Jonathan Gerber, MD 774-443-7433 Jonathan.firstname.lastname@example.org|
|Principal Investigator: Jonathan Gerber, MD|
|United States, New Jersey|
|Rutgers Cancer Institute of New Jersey||Recruiting|
|New Brunswick, New Jersey, United States, 08901|
|Contact: Dama Bhavsar 732-235-6008 email@example.com|
|Principal Investigator: Anupama Doraiswamy, MD|
|United States, Ohio|
|The Ohio State University Comprehensive Cancer Center||Recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Alice Mims, MD 614-685-6031 firstname.lastname@example.org|
|Principal Investigator: Alice Mims, MD|
|United States, Texas|
|The University of Texas MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Rabiul Islam 281-908-8956 email@example.com|
|Principal Investigator: Farhad Ravandi-Kashani, MD|
|United States, Wisconsin|
|Froedtert-Medical College of WI||Recruiting|
|Milwaukee, Wisconsin, United States, 53226|
|Contact: Ehab Atallah, MD 414-955-0209 firstname.lastname@example.org|
|Principal Investigator: Ehab Atallah, MD|
|Clinica Universidad de Navarra||Recruiting|
|Pamplona, Navarra, Spain, 31008|
|Contact: Ana Alfonso Pierola, MD +34-948-296-397 email@example.com|
|Principal Investigator: Maria del Mar Tormo Diaz, MD|
|Hospital Universitario Vall d'Hebron||Recruiting|
|Barcelona, Spain, 08035|
|Contact: Antonieta Molero Yordi, MD 34932746000 firstname.lastname@example.org|
|Principal Investigator: Antoinieta Molero Yordi, MD|
|Institut Catala d'Oncologia de l'Hospitalet de Llobregat - Hospital Duran i Reynals||Recruiting|
|Barcelona, Spain, 08908|
|Contact: Arnan S Montserrat, MD 34932607750 email@example.com|
|Principal Investigator: Arnan S Montserrat, MD|
|START Madrid - Hospital Universitario Fundacion Jimenez Diaz||Recruiting|
|Madrid, Spain, 28040|
|Contact: Daniel Morillo firstname.lastname@example.org|
|Hospital Universitario 12 de Octubre||Recruiting|
|Madrid, Spain, 28041|
|Contact: Joaquin Martinez Lopez, MD,PhD 34932607750 email@example.com|
|Principal Investigator: Joaquin Martinez Lopez, MD, PhD|
|Hospital Universitario de Salamanca||Recruiting|
|Salamanca, Spain, 58-182|
|Contact: Maria Vidriales Vicente firstname.lastname@example.org|
|Hospital Clinico Universitario de Valencia||Recruiting|
|Valencia, Spain, 46010|
|Contact: Maria del Mar Tormo Diaz, MD 34-961-961973500 email@example.com|
|Principal Investigator: Maria del Mar Tormo Diaz, MD|
|Hospital Universitario La Fe||Recruiting|
|Valencia, Spain, 46026|
|Contact: Pau Montesinos Fernandez, MD +34 96 12 45 876 firstname.lastname@example.org|
|Principal Investigator: Pau Montesinos Fernandez, MD|
|Study Director:||Vijay Jayaprakash, MBBS, PHD||Hutchison Medipharma Limited|
|Other Study ID Numbers:||
|First Posted:||February 21, 2021 Key Record Dates|
|Last Update Posted:||May 8, 2023|
|Last Verified:||May 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Acute Myeloid Leukemia
Angio-Immunoblastic T-Cell Lymphoma
Neoplasms by Site