A Phase 1b Dose Escalation Study of Lemzoparlimab in Combination With Venetoclax and/or Azacitidine in Subjects With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)
Overview
- Phase
- Phase 1
- Intervention
- Venetoclax
- Conditions
- Acute Myeloid Leukemia (AML)
- Sponsor
- AbbVie
- Enrollment
- 40
- Locations
- 29
- Primary Endpoint
- 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
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion 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%;
Exclusion Criteria
- •Participants with documented AML with acute promyelocytic leukemia and considered eligible for induction therapy.
- •Participant with documented AML having prior diagnosis of:
- •- known active central nervous system involvement with AML.
- •Participants with documented MDS having prior diagnosis of:
- •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 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;
Arms & Interventions
Lemzoparlimab + Azacitidine + Venetoclax in AML (Expansion)
Lemzoparlimab (TJ011133) co-administered with azacitidine and venetoclax in expansion cohort in participants with treatment-naïve acute myeloid leukemia (AML) who are ineligible for standard induction therapy.
Intervention: Venetoclax
Lemzoparlimab + Azacitidine + Venetoclax in MDS (Expansion)
Lemzoparlimab (TJ011133) co-administered with azacitidine and venetoclax in expansion cohort in participants with treatment-naïve higher-risk myelodysplastic syndrome (MDS).
Intervention: Lemzoparlimab
Lemzoparlimab + Azacitidine + Venetoclax in AML (Escalation)
Lemzoparlimab (TJ011133) co-administered with azacitidine and venetoclax in escalated doses in participants with treatment-naïve acute myeloid leukemia (AML) who are ineligible for standard induction therapy.
Intervention: Lemzoparlimab
Lemzoparlimab + Azacitidine + Venetoclax in AML (Escalation)
Lemzoparlimab (TJ011133) co-administered with azacitidine and venetoclax in escalated doses in participants with treatment-naïve acute myeloid leukemia (AML) who are ineligible for standard induction therapy.
Intervention: Azacitidine
Lemzoparlimab + Azacitidine + Venetoclax in AML (Escalation)
Lemzoparlimab (TJ011133) co-administered with azacitidine and venetoclax in escalated doses in participants with treatment-naïve acute myeloid leukemia (AML) who are ineligible for standard induction therapy.
Intervention: Venetoclax
Lemzoparlimab + Azacitidine + Venetoclax in MDS (Escalation)
Lemzoparlimab (TJ011133) co-administered with azacitidine and venetoclax in escalated doses in participants with treatment-naïve higher-risk myelodysplastic syndrome (MDS).
Intervention: Lemzoparlimab
Lemzoparlimab + Azacitidine + Venetoclax in MDS (Escalation)
Lemzoparlimab (TJ011133) co-administered with azacitidine and venetoclax in escalated doses in participants with treatment-naïve higher-risk myelodysplastic syndrome (MDS).
Intervention: Azacitidine
Lemzoparlimab + Azacitidine + Venetoclax in MDS (Escalation)
Lemzoparlimab (TJ011133) co-administered with azacitidine and venetoclax in escalated doses in participants with treatment-naïve higher-risk myelodysplastic syndrome (MDS).
Intervention: Venetoclax
Lemzoparlimab + Azacitidine in MDS (Escalation)
Lemzoparlimab (TJ011133) co-administered with azacitidine in escalated doses in participants with treatment-naïve higher-risk myelodysplastic syndrome (MDS).
Intervention: Lemzoparlimab
Lemzoparlimab + Azacitidine in MDS (Escalation)
Lemzoparlimab (TJ011133) co-administered with azacitidine in escalated doses in participants with treatment-naïve higher-risk myelodysplastic syndrome (MDS).
Intervention: Azacitidine
Lemzoparlimab + Azacitidine + Venetoclax in AML (Expansion)
Lemzoparlimab (TJ011133) co-administered with azacitidine and venetoclax in expansion cohort in participants with treatment-naïve acute myeloid leukemia (AML) who are ineligible for standard induction therapy.
Intervention: Lemzoparlimab
Lemzoparlimab + Azacitidine + Venetoclax in AML (Expansion)
Lemzoparlimab (TJ011133) co-administered with azacitidine and venetoclax in expansion cohort in participants with treatment-naïve acute myeloid leukemia (AML) who are ineligible for standard induction therapy.
Intervention: Azacitidine
Lemzoparlimab + Azacitidine + Venetoclax in MDS (Expansion)
Lemzoparlimab (TJ011133) co-administered with azacitidine and venetoclax in expansion cohort in participants with treatment-naïve higher-risk myelodysplastic syndrome (MDS).
Intervention: Azacitidine
Lemzoparlimab + Azacitidine + Venetoclax in MDS (Expansion)
Lemzoparlimab (TJ011133) co-administered with azacitidine and venetoclax in expansion cohort in participants with treatment-naïve higher-risk myelodysplastic syndrome (MDS).
Intervention: Venetoclax
Lemzoparlimab Monotherapy in AML (Japan Only Escalation)
Lemzoparlimab (TJ011133) administered in escalated doses in participants with treatment-naïve acute myeloid leukemia (AML) who are ineligible for standard induction therapy.
Intervention: Lemzoparlimab
Lemzoparlimab Monotherapy in MDS (Japan Only Escalation)
Lemzoparlimab (TJ011133) administered in escalated doses in participants with treatment-naïve higher-risk myelodysplastic syndrome (MDS).
Intervention: Lemzoparlimab
Outcomes
Primary Outcomes
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
Time Frame: Up to 30 days after first dose of study drug
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.
Dose Limiting Toxicities (DLTs) of Lemzoparlimab (TJ011133) as a Monotherapy in Japanese Participants with Relapsed/Refractory (R/R) AML
Time Frame: Up to 30 days after first dose of study drug
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.
DLTs of Lemzoparlimab (TJ011133) When Co-administered With Azacitidine With or Without Venetoclax in Participants With Treatment-Naïve Higher-Risk Myelodysplastic Syndrome (MDS)
Time Frame: Up to 30 days after first dose of study drug
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.
DLTs of Lemzoparlimab (TJ011133) as a Monotherapy in Japanese Participants with R/R MDS
Time Frame: Up to 30 days after first dose of study drug
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.
Secondary Outcomes
- Best Overall Response of Composite CR (CRc) for AML(Up to approximately 3 years)
- Overall Survival (OS ) for AML(Up to approximately 3 years)
- Best Overall Response of Marrow-Complete Remission (mCR), for MDS(Up to approximately 3 years)
- Platelet TI, for MDS(Up to approximately 3 years)
- Progression Free Survival (PFS), for MDS(Up to approximately 3 years)
- OS, for MDS(Up to approximately 3 years)
- Best Overall Response of Complete Remission (CR) for AML(Up to approximately 3 years)
- Duration of Response (DOR) for AML(Up to approximately 3 years)
- Best Overall Response of CR, for MDS(Up to approximately 3 years)
- Best Overall Response of CR or PR for MDS(Up to approximately 3 years)
- Hematologic Improvement (HI), for MDS(Up to approximately 3 years)
- DOR, for MDS(Up to approximately 3 years)
- Best Overall Response of CR or Complete Remission With Partial Hematologic Recovery (CRh) for AML(Up to approximately 3 years)
- Event-Free Survival (EFS) for AML(Up to approximately 3 years)
- Best Overall Response of CR or PR or mCR, for MDS(Up to approximately 3 years)
- Red Blood Cell Transfusion Independence (TI), for MDS(Up to approximately 3 years)