Acute myeloid leukemia (AML) is one of the most aggressive blood cancers, with a very low survival rate and few options for participants who are unable to undergo intensive chemotherapy, the current standard of care. This study is to evaluate how safe lemzoparlimab is and how it moves within the body when used along with azacitidine and/or venetoclax in adult participants with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Adverse events and maximum tolerated dose (MTD) of lemzoparlimab will be assessed. Lemzoparlimab (TJ011133) is being evaluated in combination with azacitidine and venetoclax for the treatment of acute myeloid leukemia (AML) and with azacitidine with/without venetoclax for myelodysplastic syndrome (MDS). Study doctors place the participants in 1 of 5 groups, called treatment arms. Each group receives a different treatment. Adult participants with a diagnosis of AML or MDS will be enrolled. Around 80 participants will be enrolled in the study in approximately 50 sites worldwide. Participants will receive lemzoparlimab (IV) once weekly (Q1W), venetoclax oral tablets once daily (QD) for 28 days (AML participants) or 14 days (MDS participants) and Azacitidine by SC or IV route QD for 7 days of each 28-day cycle. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests and checking for side effects.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Intravenous (IV) Infusion
Subcutaneous Injection or Intravenous (IV) Injection/Infusion
Oral Tablet
University of Alabama at Birmingham - Main /ID# 227071
Birmingham, Alabama, United States
Norton Cancer Institute - St Matthews /ID# 228378
Louisville, Kentucky, United States
Massachusetts General Hospital /ID# 227273
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center /ID# 231083
Boston, Massachusetts, United States
University of Michigan /ID# 227030
Ann Arbor, Michigan, United States
Dose Limiting Toxicities (DLTs) of Lemzoparlimab (TJ011133) When Co-administered With Venetoclax and Azacitidine in Participants With Treatment-Naïve Acute Myeloid Leukemia (AML) Ineligible for Standard Induction Therapy
DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications and occurring during the first 4 weeks after administration of the first dose and that meets additional criteria as described in the protocol.
Time frame: Up to 30 days after first dose of study drug
DLTs of Lemzoparlimab (TJ011133) When Co-administered With Azacitidine With or Without Venetoclax in Participants With Treatment-Naïve Higher-Risk Myelodysplastic Syndrome (MDS)
DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications and occurring during the first 4 weeks after administration of the first dose and that meets additional criteria as described in the protocol.
Time frame: Up to 30 days after first dose of study drug
Dose Limiting Toxicities (DLTs) of Lemzoparlimab (TJ011133) as a Monotherapy in Japanese Participants with Relapsed/Refractory (R/R) AML
DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications and occurring during the first 4 weeks after administration of the first dose and that meets additional criteria as described in the protocol.
Time frame: Up to 30 days after first dose of study drug
DLTs of Lemzoparlimab (TJ011133) as a Monotherapy in Japanese Participants with R/R MDS
DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications and occurring during the first 4 weeks after administration of the first dose and that meets additional criteria as described in the protocol.
Time frame: Up to 30 days after first dose of study drug
Best Overall Response of Complete Remission (CR) for AML
Best overall response of complete remission (CR), defined as achieving CR according to modified international working group (IWG) 2003 criteria for AML.
Time frame: Up to approximately 3 years
Best Overall Response of Composite CR (CRc) for AML
Best overall response of composite CR (CRc), \[CR or CR with incomplete blood count recovery (CRi)\] according to modified IWG 2003 criteria for AML.
Time frame: Up to approximately 3 years
Best Overall Response of CR or Complete Remission With Partial Hematologic Recovery (CRh) for AML
Best overall response of CR or CRh, defined according to modified IWG 2003 criteria for AML.
Time frame: Up to approximately 3 years
Duration of Response (DOR) for AML
Duration of response (DOR), defined for participants who achieve a best overall response, as the time from the first occurrence of response to disease progression/relapse from CR, CRi or CRh or death from disease progression, whichever occurs first.
Time frame: Up to approximately 3 years
Event-Free Survival (EFS) for AML
Event-free survival (EFS), defined as time from first dose of any study drug (lemzoparlimab or venetoclax or azacitidine) to the date of progressive disease (PD), relapse from CR or CRi, treatment failure defined as failure to achieve CR, CRi or MLFS after at least 6 cycles of study treatment, or death from any cause, whichever occurs first.
Time frame: Up to approximately 3 years
Overall Survival (OS ) for AML
Overall survival (OS), defined as the time from the date of the first dose of any study drug (lemzoparlimab or venetoclax or azacitidine) to death from any cause.
Time frame: Up to approximately 3 years
Best Overall Response of CR, for MDS
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University of Pennsylvania /ID# 227024
Philadelphia, Pennsylvania, United States
UPMC Hillman Cancer Ctr /ID# 228048
Pittsburgh, Pennsylvania, United States
MD Anderson Cancer Center at Texas Medical Center /ID# 227019
Houston, Texas, United States
University of Virginia Health /ID# 227363
Charlottesville, Virginia, United States
Liverpool Hospital /ID# 227723
Liverpool, New South Wales, Australia
...and 19 more locations
Best overall response of CR per the modified IWG 2006 criteria for MDS.
Time frame: Up to approximately 3 years
Best Overall Response of Marrow-Complete Remission (mCR), for MDS
Best overall response of marrow-complete remission (mCR), per the modified IWG 2006 criteria for MDS.
Time frame: Up to approximately 3 years
Best Overall Response of CR or PR for MDS
Best overall response of CR or PR, per the modified IWG 2006 criteria for MDS.
Time frame: Up to approximately 3 years
Best Overall Response of CR or PR or mCR, for MDS
Best overall response of CR or PR or mCR, per the modified IWG 2006 criteria for MDS.
Time frame: Up to approximately 3 years
Hematologic Improvement (HI), for MDS
Hematologic improvement (HI), defined as a participant achieving erythroid/platelet/neutrophil responses.
Time frame: Up to approximately 3 years
Red Blood Cell Transfusion Independence (TI), for MDS
Red blood cell transfusion independence (TI), defined as a participant who is transfusion dependent at baseline achieved TI post-baseline.
Time frame: Up to approximately 3 years
Platelet TI, for MDS
Platelet TI, defined as a participant who is transfusion dependent at baseline achieved TI post-baseline.
Time frame: Up to approximately 3 years
DOR, for MDS
DOR, defined for participants who achieve a best overall response, as the time from the first occurrence of response (CR or mCR or PR) to disease progression or death, whichever occurs first.
Time frame: Up to approximately 3 years
Progression Free Survival (PFS), for MDS
Progression Free Survival (PFS) defined as the time from the date of the first dose of any study drug to PD or death from any cause.
Time frame: Up to approximately 3 years
OS, for MDS
OS, defined as the time from the date of the first dose of any study drug to death from any cause.
Time frame: Up to approximately 3 years