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AzTrials

Acute Myeloid Leukemia (AML)Phase 1NCT04912063

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

A Phase 1 study testing Lemzoparlimab, Azacitidine and Venetoclax in people with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS), run by AbbVie at 29 sites in 7 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Lemzoparlimab, Azacitidine and Venetoclax
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
29 sitesin 7 countries
Study dates
25 Jun 2021to 9 May 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

29 sites in 7 countries.

29 sites in 7 countries

United States9 sites

  • University of Michigan /ID# 227030

    Ann Arbor, Michigan, 48109

  • University of Alabama at Birmingham - Main /ID# 227071

    Birmingham, Alabama, 35233

  • Massachusetts General Hospital /ID# 227273

    Boston, Massachusetts, 02114

  • Beth Israel Deaconess Medical Center /ID# 231083

    Boston, Massachusetts, 02215-5400

  • University of Virginia Health /ID# 227363

    Charlottesville, Virginia, 22908

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

    Houston, Texas, 77030-4000

  • Norton Cancer Institute - St Matthews /ID# 228378

    Louisville, Kentucky, 40207

  • University of Pennsylvania /ID# 227024

    Philadelphia, Pennsylvania, 19104

  • UPMC Hillman Cancer Ctr /ID# 228048

    Pittsburgh, Pennsylvania, 15232

Other trials in United States

Germany4 sites

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

    Dresden, 01307

  • Marien Hospital Duesseldorf /ID# 227751

    Düsseldorf, North Rhine-Westphalia, 40479

  • Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 227748

    Hamburg, 20246

  • Universitaetsklinikum Leipzig /ID# 227750

    Leipzig, Saxony, 04103

Other trials in Germany

Israel4 sites

  • Hadassah Medical Center-Hebrew University /ID# 227275

    Jerusalem, Jerusalem, 91120

  • Rabin Medical Center /ID# 227738

    Petah Tikva, 4941492

  • The Chaim Sheba Medical Center /ID# 227389

    Ramat Gan, Tel Aviv, 5265601

  • Tel Aviv Sourasky Medical Center /ID# 227387

    Tel Aviv, Tel Aviv, 6423906

Other trials in Israel

Japan4 sites

  • Kyushu University Hospital /ID# 232564

    Fukuoka, Fukuoka, 812-8582

  • National Cancer Center Hospital East /ID# 232498

    Kashiwa-shi, Chiba, 277-8577

  • Yamagata University Hospital /ID# 232451

    Yamagata, Yamagata, 990-9585

  • University of Fukui Hospital /ID# 232466

    Yoshida-gun, Fukui, 910-1193

Other trials in Japan

Italy3 sites

  • IRCCS Azienda Ospedaliero-Universitaria di Bologna /ID# 226950

    Bologna, 40138

  • ASST Grande Ospedale Metropolitano Niguarda /ID# 226952

    Milan, 20162

  • Istituto Clinico Humanitas /ID# 226948

    Rozzano, Milano, 20089

Other trials in Italy

Spain3 sites

  • Hospital Clinic de Barcelona /ID# 227772

    Barcelona, 08036

  • Hospital Universitario Fundacion Jimenez Diaz /ID# 227771

    Madrid, 28040

  • Hospital Universitario Virgen de la Victoria /ID# 227770

    Málaga, 29010

Other trials in Spain

Australia2 sites

  • Austin Health /ID# 227717

    Heidelberg, Victoria, 3084

  • Liverpool Hospital /ID# 227723

    Liverpool, New South Wales, 2170

Other trials in Australia

About this study

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)

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.

Read more

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.

Being tested
Lemzoparlimab, Azacitidine, Venetoclax
Keywords
Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), Lemzoparlimab, TJ011133, ABBV-IMAB-TJC4, Venetoclax, ABT-199, GDC-0199, VENCLEXTA, VENCLYXTO, Azacitidine, Cancer
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LemzoparlimabDrug

    Also called TJ011133, ABBV-IMAB-TJC4

    Intravenous (IV) Infusion

  • AzacitidineDrug

    Subcutaneous Injection or Intravenous (IV) Injection/Infusion

  • VenetoclaxDrug

    Also called Venclexta, Venclyxto, ABT-199, GDC-0199

    Oral Tablet

Study groups in NCT04912063
Study groupRoleWhat they receive
Lemzoparlimab + Azacitidine + Venetoclax in AML (Escalation)ExperimentalLemzoparlimab (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.
Receives: Drug: Lemzoparlimab; Drug: Azacitidine; Drug: Venetoclax
Lemzoparlimab + Azacitidine + Venetoclax in MDS (Escalation)ExperimentalLemzoparlimab (TJ011133) co-administered with azacitidine and venetoclax in escalated doses in participants with treatment-naïve higher-risk myelodysplastic syndrome (MDS).
Receives: Drug: Lemzoparlimab; Drug: Azacitidine; Drug: Venetoclax
Lemzoparlimab + Azacitidine in MDS (Escalation)ExperimentalLemzoparlimab (TJ011133) co-administered with azacitidine in escalated doses in participants with treatment-naïve higher-risk myelodysplastic syndrome (MDS).
Receives: Drug: Lemzoparlimab; Drug: Azacitidine
Lemzoparlimab + Azacitidine + Venetoclax in AML (Expansion)ExperimentalLemzoparlimab (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.
Receives: Drug: Lemzoparlimab; Drug: Azacitidine; Drug: Venetoclax
Lemzoparlimab + Azacitidine + Venetoclax in MDS (Expansion)ExperimentalLemzoparlimab (TJ011133) co-administered with azacitidine and venetoclax in expansion cohort in participants with treatment-naïve higher-risk myelodysplastic syndrome (MDS).
Receives: Drug: Lemzoparlimab; Drug: Azacitidine; Drug: Venetoclax
Lemzoparlimab Monotherapy in AML (Japan Only Escalation)ExperimentalLemzoparlimab (TJ011133) administered in escalated doses in participants with treatment-naïve acute myeloid leukemia (AML) who are ineligible for standard induction therapy.
Receives: Drug: Lemzoparlimab
Lemzoparlimab Monotherapy in MDS (Japan Only Escalation)ExperimentalLemzoparlimab (TJ011133) administered in escalated doses in participants with treatment-naïve higher-risk myelodysplastic syndrome (MDS).
Receives: Drug: Lemzoparlimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 30 days after first dose of study drug

  2. 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.

    Measured: Up to 30 days after first dose of study drug

  3. 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.

    Measured: Up to 30 days after first dose of study drug

  4. 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.

    Measured: Up to 30 days after first dose of study drug

Secondary outcomes (16)

  1. 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.

    Measured: Up to approximately 3 years

  2. 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.

    Measured: Up to approximately 3 years

  3. 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.

    Measured: Up to approximately 3 years

  4. 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.

    Measured: Up to approximately 3 years

  5. 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.

    Measured: Up to approximately 3 years

  6. 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.

    Measured: Up to approximately 3 years

  7. Best Overall Response of CR, for MDS

    Best overall response of CR per the modified IWG 2006 criteria for MDS.

    Measured: Up to approximately 3 years

  8. 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.

    Measured: Up to approximately 3 years

  9. Best Overall Response of CR or PR for MDS

    Best overall response of CR or PR, per the modified IWG 2006 criteria for MDS.

    Measured: Up to approximately 3 years

  10. 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.

    Measured: Up to approximately 3 years

  11. Hematologic Improvement (HI), for MDS

    Hematologic improvement (HI), defined as a participant achieving erythroid/platelet/neutrophil responses.

    Measured: Up to approximately 3 years

  12. 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.

    Measured: Up to approximately 3 years

  13. Platelet TI, for MDS

    Platelet TI, defined as a participant who is transfusion dependent at baseline achieved TI post-baseline.

    Measured: Up to approximately 3 years

  14. 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.

    Measured: Up to approximately 3 years

  15. 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.

    Measured: Up to approximately 3 years

  16. OS, for MDS

    OS, defined as the time from the date of the first dose of any study drug to death from any cause.

    Measured: Up to approximately 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jun 2021
  2. Study start25 Jun 2021
  3. Primary completion9 May 2023
  4. Study completion9 May 2023

Why it stopped: Strategic considerations

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04912063
Sponsor's protocol ID
M20-866
Other IDs
2021-000514-41
Status last verified
Feb 2024
First submitted
28 May 2021
Last updated
26 Feb 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Lemzoparlimab, Azacitidine and Venetoclax in people with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS), run by AbbVie at 29 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 26 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in United States, Germany, Israel, Japan, Italy and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Strategic considerations). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04912063.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2024.

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