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

NCT04912063 | Terminated Phase 1 FDA Drug

• 2 other identifiers: M20-8662021-000514-41
• Study Type: interventional
• Target: 40
• Locations: 7 countries
• Sites: 29

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)

Keywords

Acute Myeloid Leukemia (AML); Myelodysplastic Syndrome (MDS); Lemzoparlimab; TJ011133; ABBV-IMAB-TJC4; Venetoclax; ABT-199; GDC-0199; VENCLEXTA; VENCLYXTO; Azacitidine; Cancer

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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 Outcomes (16)

• Best Overall Response of Complete Remission (CR) for AML

  Up to approximately 3 years

• Best Overall Response of Composite CR (CRc) for AML

  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

• Duration of Response (DOR) for AML

  Up to approximately 3 years

• Event-Free Survival (EFS) for AML

  Up to approximately 3 years

Study Arms (7)

Lemzoparlimab + Azacitidine + Venetoclax in AML (Escalation)

EXPERIMENTAL

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.

Drug: Lemzoparlimab; Drug: Azacitidine; Drug: Venetoclax

Lemzoparlimab + Azacitidine + Venetoclax in MDS (Escalation)

EXPERIMENTAL

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

Drug: Lemzoparlimab; Drug: Azacitidine; Drug: Venetoclax

Lemzoparlimab + Azacitidine in MDS (Escalation)

EXPERIMENTAL

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

Drug: Lemzoparlimab; Drug: Azacitidine

Lemzoparlimab + Azacitidine + Venetoclax in AML (Expansion)

EXPERIMENTAL

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.

Drug: Lemzoparlimab; Drug: Azacitidine; Drug: Venetoclax

Lemzoparlimab + Azacitidine + Venetoclax in MDS (Expansion)

EXPERIMENTAL

Lemzoparlimab (TJ011133) co-administered with azacitidine and venetoclax in expansion cohort in participants with treatment-naïve higher-risk myelodysplastic syndrome (MDS).

Drug: Lemzoparlimab; Drug: Azacitidine; Drug: Venetoclax

Lemzoparlimab Monotherapy in AML (Japan Only Escalation)

EXPERIMENTAL

Lemzoparlimab (TJ011133) administered in escalated doses in participants with treatment-naïve acute myeloid leukemia (AML) who are ineligible for standard induction therapy.

Drug: Lemzoparlimab

Lemzoparlimab Monotherapy in MDS (Japan Only Escalation)

EXPERIMENTAL

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

Drug: Lemzoparlimab

Interventions

Lemzoparlimab DRUG

Intravenous (IV) Infusion

Also known as: TJ011133, ABBV-IMAB-TJC4

Lemzoparlimab + Azacitidine + Venetoclax in AML (Escalation); Lemzoparlimab + Azacitidine + Venetoclax in AML (Expansion); Lemzoparlimab + Azacitidine + Venetoclax in MDS (Escalation); Lemzoparlimab + Azacitidine + Venetoclax in MDS (Expansion); Lemzoparlimab + Azacitidine in MDS (Escalation); Lemzoparlimab Monotherapy in AML (Japan Only Escalation); Lemzoparlimab Monotherapy in MDS (Japan Only Escalation)

Azacitidine DRUG

Subcutaneous Injection or Intravenous (IV) Injection/Infusion

Lemzoparlimab + Azacitidine + Venetoclax in AML (Escalation); Lemzoparlimab + Azacitidine + Venetoclax in AML (Expansion); Lemzoparlimab + Azacitidine + Venetoclax in MDS (Escalation); Lemzoparlimab + Azacitidine + Venetoclax in MDS (Expansion); Lemzoparlimab + Azacitidine in MDS (Escalation)

Venetoclax DRUG

Oral Tablet

Also known as: Venclexta, Venclyxto, ABT-199, GDC-0199

Lemzoparlimab + Azacitidine + Venetoclax in AML (Escalation); Lemzoparlimab + Azacitidine + Venetoclax in AML (Expansion); Lemzoparlimab + Azacitidine + Venetoclax in MDS (Escalation); Lemzoparlimab + Azacitidine + Venetoclax in MDS (Expansion)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• AbbVie: lead

Study Sites (29)

University of Alabama at Birmingham - Main /ID# 227071

Birmingham, Alabama, 35233, United States

Location

Norton Cancer Institute - St Matthews /ID# 228378

Louisville, Kentucky, 40207, United States

Location

Massachusetts General Hospital /ID# 227273

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center /ID# 231083

Boston, Massachusetts, 02215-5400, United States

Location

University of Michigan /ID# 227030

Ann Arbor, Michigan, 48109, United States

Location

University of Pennsylvania /ID# 227024

Philadelphia, Pennsylvania, 19104, United States

Location

UPMC Hillman Cancer Ctr /ID# 228048

Pittsburgh, Pennsylvania, 15232, United States

Location

MD Anderson Cancer Center at Texas Medical Center /ID# 227019

Houston, Texas, 77030-4000, United States

Location

University of Virginia Health /ID# 227363

Charlottesville, Virginia, 22908, United States

Location

Liverpool Hospital /ID# 227723

Liverpool, New South Wales, 2170, Australia

Location

Austin Health /ID# 227717

Heidelberg, Victoria, 3084, Australia

Location

Marien Hospital Duesseldorf /ID# 227751

Düsseldorf, North Rhine-Westphalia, 40479, Germany

Location

Universitaetsklinikum Leipzig /ID# 227750

Leipzig, Saxony, 04103, Germany

Location

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

Dresden, 01307, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 227748

Hamburg, 20246, Germany

Location

Hadassah Medical Center-Hebrew University /ID# 227275

Jerusalem, Jerusalem, 91120, Israel

Location

The Chaim Sheba Medical Center /ID# 227389

Ramat Gan, Tel Aviv, 5265601, Israel

Location

Tel Aviv Sourasky Medical Center /ID# 227387

Tel Aviv, Tel Aviv, 6423906, Israel

Location

Rabin Medical Center /ID# 227738

Petah Tikva, 4941492, Israel

Location

Istituto Clinico Humanitas /ID# 226948

Rozzano, Milano, 20089, Italy

Location

IRCCS Azienda Ospedaliero-Universitaria di Bologna /ID# 226950

Bologna, 40138, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda /ID# 226952

Milan, 20162, Italy

Location

National Cancer Center Hospital East /ID# 232498

Kashiwa-shi, Chiba, 277-8577, Japan

Location

University of Fukui Hospital /ID# 232466

Yoshida-gun, Fukui, 910-1193, Japan

Location

Kyushu University Hospital /ID# 232564

Fukuoka, Fukuoka, 812-8582, Japan

Location

Yamagata University Hospital /ID# 232451

Yamagata, Yamagata, 990-9585, Japan

Location

Hospital Clinic de Barcelona /ID# 227772

Barcelona, 08036, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz /ID# 227771

Madrid, 28040, Spain

Location

Hospital Universitario Virgen de la Victoria /ID# 227770

Málaga, 29010, Spain

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Neoplasms

Interventions

Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2021
• First Posted: June 3, 2021
• Study Start: June 25, 2021
• Primary Completion: May 9, 2023
• Study Completion: May 9, 2023
• Last Updated: February 26, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (4); JP (4); IL (4); IT (3); US (9); ES (3); AU (2)