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

NCT ID: NCT04912063

Last Updated: 2024-02-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-25
• Study Completion Date: 2023-05-09

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.

Conditions

Acute Myeloid Leukemia (AML); Myelodysplastic Syndrome (MDS)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Lemzoparlimab

Intervention Type: DRUG

Intravenous (IV) Infusion

Azacitidine

Intervention Type: DRUG

Subcutaneous Injection or Intravenous (IV) Injection/Infusion

Venetoclax

Intervention Type: DRUG

Oral Tablet

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).

Group Type: EXPERIMENTAL

Lemzoparlimab

Intervention Type: DRUG

Intravenous (IV) Infusion

Azacitidine

Intervention Type: DRUG

Subcutaneous Injection or Intravenous (IV) Injection/Infusion

Venetoclax

Intervention Type: DRUG

Oral Tablet

Lemzoparlimab + Azacitidine in MDS (Escalation)

Lemzoparlimab (TJ011133) co-administered with azacitidine in escalated doses in participants with treatment-naïve higher-risk myelodysplastic syndrome (MDS).

Group Type: EXPERIMENTAL

Lemzoparlimab

Intervention Type: DRUG

Intravenous (IV) Infusion

Azacitidine

Intervention Type: DRUG

Subcutaneous Injection or Intravenous (IV) Injection/Infusion

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.

Group Type: EXPERIMENTAL

Lemzoparlimab

Intervention Type: DRUG

Intravenous (IV) Infusion

Azacitidine

Intervention Type: DRUG

Subcutaneous Injection or Intravenous (IV) Injection/Infusion

Venetoclax

Intervention Type: DRUG

Oral Tablet

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).

Group Type: EXPERIMENTAL

Lemzoparlimab

Intervention Type: DRUG

Intravenous (IV) Infusion

Azacitidine

Intervention Type: DRUG

Subcutaneous Injection or Intravenous (IV) Injection/Infusion

Venetoclax

Intervention Type: DRUG

Oral Tablet

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.

Group Type: EXPERIMENTAL

Lemzoparlimab

Intervention Type: DRUG

Intravenous (IV) Infusion

Lemzoparlimab Monotherapy in MDS (Japan Only Escalation)

Lemzoparlimab (TJ011133) administered in escalated doses in participants with treatment-naïve higher-risk myelodysplastic syndrome (MDS).

Group Type: EXPERIMENTAL

Lemzoparlimab

Intervention Type: DRUG

Intravenous (IV) Infusion

Interventions

Lemzoparlimab

Intravenous (IV) Infusion

Intervention Type: DRUG

Azacitidine

Subcutaneous Injection or Intravenous (IV) Injection/Infusion

Intervention Type: DRUG

Venetoclax

Oral Tablet

Intervention Type: DRUG

Other Intervention Names

TJ011133; ABBV-IMAB-TJC4; Venclexta; Venclyxto; ABT-199; GDC-0199

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%;
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

ABBVIE INC.

Role: STUDY_DIRECTOR

AbbVie

Locations

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

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

Austin Health /ID# 227717

Heidelberg, Victoria, Australia

Marien Hospital Duesseldorf /ID# 227751

Düsseldorf, North Rhine-Westphalia, Germany

Universitaetsklinikum Leipzig /ID# 227750

Leipzig, Saxony, Germany

Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 227749

Dresden, , Germany

Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 227748

Hamburg, , Germany

Hadassah Medical Center-Hebrew University /ID# 227275

Jerusalem, Jerusalem, Israel

The Chaim Sheba Medical Center /ID# 227389

Ramat Gan, Tel Aviv, Israel

Tel Aviv Sourasky Medical Center /ID# 227387

Tel Aviv, Tel Aviv, Israel

Rabin Medical Center /ID# 227738

Petah Tikva, , Israel

Istituto Clinico Humanitas /ID# 226948

Rozzano, Milano, Italy

IRCCS Azienda Ospedaliero-Universitaria di Bologna /ID# 226950

Bologna, , Italy

ASST Grande Ospedale Metropolitano Niguarda /ID# 226952

Milan, , Italy

National Cancer Center Hospital East /ID# 232498

Kashiwa-shi, Chiba, Japan

University of Fukui Hospital /ID# 232466

Yoshida-gun, Fukui, Japan

Kyushu University Hospital /ID# 232564

Fukuoka, Fukuoka, Japan

Yamagata University Hospital /ID# 232451

Yamagata, Yamagata, Japan

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

Málaga, , Spain

Countries

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

Other Identifiers

2021-000514-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M20-866

Identifier Type: -

Identifier Source: org_study_id