Study to Evaluate Adverse Events and Movement of Lemzoparlimab in Body When Used Intravenously (IV) With Azacitidine Subcutaneously or IV and Venetoclax Orally in Participants With Acute Myeloid Leukemia and With Azacitidine With or Without Venetoclax in Participants With Myelodysplastic Syndrome

Acute Myeloid Leukemia (AML) Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04912063
• Other study ID #: M20-866
• Secondary ID: 2021-000514-41
• Status: Terminated
• Phase: Phase 1
• Start date: June 25, 2021
• Est. completion date: May 9, 2023

Study information

• Verified date: February 2024
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 40
• Est. completion date: May 9, 2023
• Est. primary completion date: May 9, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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%;
• Creatinine clearance >= 30 mL/min to < 45 mL/min;
• Moderate hepatic impairment with total bilirubin > 1.5 to <= 3.0 × 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.

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;
• 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 Conditions & MeSH terms

• Acute Myeloid Leukemia (AML)
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndrome (MDS)
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• Lemzoparlimab
Intravenous (IV) Infusion
• Azacitidine
Subcutaneous Injection or Intravenous (IV) Injection/Infusion
• Venetoclax
Oral Tablet

Locations

Country	Name	City	State
Australia	Austin Health /ID# 227717	Heidelberg	Victoria
Australia	Liverpool Hospital /ID# 227723	Liverpool	New South Wales
Germany	Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 227749	Dresden
Germany	Marien Hospital Duesseldorf /ID# 227751	Duesseldorf	Nordrhein-Westfalen
Germany	Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 227748	Hamburg
Germany	Universitaetsklinikum Leipzig /ID# 227750	Leipzig	Sachsen
Israel	Hadassah Medical Center-Hebrew University /ID# 227275	Jerusalem	Yerushalayim
Israel	Rabin Medical Center /ID# 227738	Petakh Tikva
Israel	The Chaim Sheba Medical Center /ID# 227389	Ramat Gan	Tel-Aviv
Israel	Tel Aviv Sourasky Medical Center /ID# 227387	Tel Aviv-Yafo	Tel-Aviv
Italy	IRCCS Azienda Ospedaliero-Universitaria di Bologna /ID# 226950	Bologna
Italy	ASST Grande Ospedale Metropolitano Niguarda /ID# 226952	Milano
Italy	Istituto Clinico Humanitas /ID# 226948	Rozzano	Milano
Japan	Kyushu University Hospital /ID# 232564	Fukuoka-shi	Fukuoka
Japan	National Cancer Center Hospital East /ID# 232498	Kashiwa-shi	Chiba
Japan	Yamagata University Hospital /ID# 232451	Yamagata-shi	Yamagata
Japan	University of Fukui Hospital /ID# 232466	Yoshida-gun	Fukui
Spain	Hospital Clinic de Barcelona /ID# 227772	Barcelona
Spain	Hospital Universitario Fundacion Jimenez Diaz /ID# 227771	Madrid
Spain	Hospital Universitario Virgen de la Victoria /ID# 227770	Malaga
United States	University of Michigan /ID# 227030	Ann Arbor	Michigan
United States	University of Alabama at Birmingham - Main /ID# 227071	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center /ID# 231083	Boston	Massachusetts
United States	Massachusetts General Hospital /ID# 227273	Boston	Massachusetts
United States	University of Virginia Health /ID# 227363	Charlottesville	Virginia
United States	MD Anderson Cancer Center at Texas Medical Center /ID# 227019	Houston	Texas
United States	Norton Cancer Institute - St Matthews /ID# 228378	Louisville	Kentucky
United States	University of Pennsylvania /ID# 227024	Philadelphia	Pennsylvania
United States	UPMC Hillman Cancer Ctr /ID# 228048	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Germany,  Israel,  Italy,  Japan,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 30 days after first dose of study drug
Primary	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.	Up to 30 days after first dose of study drug
Primary	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.	Up to 30 days after first dose of study drug
Primary	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.	Up to 30 days after first dose of study drug
Secondary	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.	Up to approximately 3 years
Secondary	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.	Up to approximately 3 years
Secondary	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.	Up to approximately 3 years
Secondary	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.	Up to approximately 3 years
Secondary	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.	Up to approximately 3 years
Secondary	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.	Up to approximately 3 years
Secondary	Best Overall Response of CR, for MDS	Best overall response of CR per the modified IWG 2006 criteria for MDS.	Up to approximately 3 years
Secondary	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.	Up to approximately 3 years
Secondary	Best Overall Response of CR or PR for MDS	Best overall response of CR or PR, per the modified IWG 2006 criteria for MDS.	Up to approximately 3 years
Secondary	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.	Up to approximately 3 years
Secondary	Hematologic Improvement (HI), for MDS	Hematologic improvement (HI), defined as a participant achieving erythroid/platelet/neutrophil responses.	Up to approximately 3 years
Secondary	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.	Up to approximately 3 years
Secondary	Platelet TI, for MDS	Platelet TI, defined as a participant who is transfusion dependent at baseline achieved TI post-baseline.	Up to approximately 3 years
Secondary	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.	Up to approximately 3 years
Secondary	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.	Up to approximately 3 years
Secondary	OS, for MDS	OS, defined as the time from the date of the first dose of any study drug to death from any cause.	Up to approximately 3 years