[M20-866] AML and MDS: Lemzoparlimab in Combination with Venetoclax and/or Azacitidine

JRCT ID: jRCT2051210150

Registered date:09/01/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS)
• Date of first enrollment: 18/04/2022
• Target sample size: 80
• Countries of recruitment: Canada,Japan,Israel,Japan,United Kingdom,Japan,US,Japan,Germany,Japan,Italy,Japan,Spain,Japan
• Study type: Interventional

Intervention(s)

- Lemzoparlimab plus Azacitidine plus Venetoclax in AML (Escalation)
Lemzoparlimab (TJ011133) co-administered with azacitidine and venetoclax in escalated doses in participants with treatment-naive acute myeloid leukemia (AML) who are ineligible for standard induction therapy.
- Lemzoparlimab plus Azacitidine plus Venetoclax in MDS (Escalation)
Lemzoparlimab (TJ011133) co-administered with azacitidine and venetoclax in escalated doses in participants with treatment-naive higher-risk myelodysplastic syndrome (MDS).
- Lemzoparlimab plus Azacitidine in MDS (Escalation)
Lemzoparlimab (TJ011133) co-administered with azacitidine in escalated doses in participants with treatment-naive higher-risk myelodysplastic syndrome (MDS).
- Lemzoparlimab plus Azacitidine plus Venetoclax in AML (Expansion)
Lemzoparlimab (TJ011133) co-administered with azacitidine and venetoclax in expansion cohort in participants with treatment-naive acute myeloid leukemia (AML) who are ineligible for standard induction therapy.
- Lemzoparlimab plus Azacitidine plus Venetoclax in MDS (Expansion)
Lemzoparlimab (TJ011133) co-administered with azacitidine and venetoclax in expansion cohort in participants with treatment-naive higher-risk myelodysplastic syndrome (MDS).
- Lemzoparlimab Monotherapy in AML (Japan Only Escalation)
Lemzoparlimab (TJ011133) administered in escalated doses in participants with treatment-naive acute myeloid leukemia (AML) who are ineligible for standard induction therapy.
- Lemzoparlimab Monotherapy in MDS (Japan Only Escalation)
Lemzoparlimab (TJ011133) administered in escalated doses in participants with treatment-naive higher-risk myelodysplastic syndrome (MDS).

Outcome(s)

• Primary Outcome: Dose Limiting Toxicities (DLTs)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Documented confirmation of acute myeloid leukemia (AML) according to the World Health Organization (WHO) criteria, previously untreated [OR]
- Documented diagnosis of previously untreated de novo myelodysplastic syndrome (MDS) according to the 2017 WHO classification with presence of < 20% bone marrow blasts per marrow biopsy/aspirate.
- Participants with documented MDS must meet the following disease activity criteria:
-- Overall revised international prognostic scoring system (IPSS-R) score > 3 (intermediate, high, or very high);
-- Eastern cooperative oncology group (ECOG) performance status of 0 to 2;
-- Hematopoietic stem cell transplant (HSCT) ineligible, or participant who chooses not to undergo HSCT.
- Participants with documented AML with adverse cytogenetic and/or molecular risk, and must be considered ineligible for induction therapy defined by the following:
-- >= 75 years of age; [OR]
-- >= 18 to 74 years of age with at least one of the following comorbidities:
--- Eastern cooperative oncology group (ECOG) performance status of 2 to 3;
--- Cardiac history of congestive heart failure requiring treatment or ejection fraction <= 50% or chronic stable angina;
--- Diffusion capacity of lung (DLCO) <= 65% or forced expiratory volume during the first second (FEV1) <= 65%;
--- Creatinine clearance >= 30 mL/min to < 45 mL/min;
--- Moderate hepatic impairment with total bilirubin > 1.5 to <= 3.0 x upper limit of normal (ULN);
--- Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy or the participant declines to receive intensive chemotherapy.

Japan Safety Lead-In Phase:
- Documented confirmation of AML according to WHO criteria, relapsed or refractory (R/R) disease without other standard of care treatments.
- Documented diagnosis of MDS according to the 2017 WHO classification with presence of < 20% bone marrow blasts per marrow biopsy/aspirate, with intermediate- and high-risk relapsed/refractory MDS.
- Documented MDS must meet the following disease activity criteria:
-- ECOG performance status of 0 to 2.

Exclude criteria

- Participants with documented AML with acute promyelocytic leukemia and considered eligible for induction therapy.
- Participant with documented AML having prior diagnosis of:
-- Chronic myeloid leukemia with or without BCR-ABL1 translocation and AML with BCR-ABL1 translocation;
-- known active central nervous system involvement with AML.
- Participants with documented MDS having prior diagnosis of:
-- Therapy-related MDS;
-- MDS evolving from a pre-existing myeloproliferative neoplasm (MPN);
-- MDS/MPN including chronic myelomonocytic leukemia, atypical chronic myeloid leukemia, juvenile myelomonocytic leukemia and unclassifiable MDS/MPN.
- History of allogeneic HSCT or solid organ transplantation.
- Previous exposure to azacitidine or venetoclax or anti-CD47 therapies.
- History of an active malignancy within the past 2 years prior to Screening, with the exception of:
-- Adequately treated carcinoma in situ of the cervix uteri or carcinoma in situ of the breast;
-- Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin;
-- Asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy;
-- Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
- Conditions that could interfere with drug absorption including but not limited to short bowel syndrome.

Japan Safety Lead-In Phase:
- Documented AML have Acute Promyelocytic Leukemia.
- Participant with documented AML having prior diagnosis of:
-- Chronic myeloid leukemia with or without BCR-ABL1 translocation and AML with BCR-ABL1 translocation.
- Participants with documented MDS having prior diagnosis of:
-- Therapy-related MDS.

Related Information

• Primary Sponsor: Satomi Natsuko
• Secondary ID(s): NCT04912063