Clinical trial NCT04912063: 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
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
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
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2021-06-03
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
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
timeFrame: Up to 30 days after first dose of study drug
measure: DLTs of Lemzoparlimab (TJ011133) When Co-administered With Azacitidine With or Without Venetoclax in Participants With Treatment-Naïve Higher-Risk Myelodysplastic Syndrome (MDS)
timeFrame: Up to 30 days after first dose of study drug
measure: Dose Limiting Toxicities (DLTs) of Lemzoparlimab (TJ011133) as a Monotherapy in Japanese Participants with Relapsed/Refractory (R/R) AML
timeFrame: Up to 30 days after first dose of study drug
measure: DLTs of Lemzoparlimab (TJ011133) as a Monotherapy in Japanese Participants with R/R MDS
timeFrame: Up to 30 days after first dose of study drug
Secondary outcomes:
measure: Best Overall Response of Complete Remission (CR) for AML
timeFrame: Up to approximately 3 years
measure: Best Overall Response of Composite CR (CRc) for AML
timeFrame: Up to approximately 3 years
measure: Best Overall Response of CR or Complete Remission With Partial Hematologic Recovery (CRh) for AML
timeFrame: Up to approximately 3 years
measure: Duration of Response (DOR) for AML
timeFrame: Up to approximately 3 years
measure: Event-Free Survival (EFS) for AML
timeFrame: Up to approximately 3 years
measure: Overall Survival (OS ) for AML
timeFrame: Up to approximately 3 years
measure: Best Overall Response of CR, for MDS
timeFrame: Up to approximately 3 years
measure: Best Overall Response of Marrow-Complete Remission (mCR), for MDS
timeFrame: Up to approximately 3 years
measure: Best Overall Response of CR or PR for MDS
timeFrame: Up to approximately 3 years
measure: Best Overall Response of CR or PR or mCR, for MDS
timeFrame: Up to approximately 3 years
measure: Hematologic Improvement (HI), for MDS
timeFrame: Up to approximately 3 years
measure: Red Blood Cell Transfusion Independence (TI), for MDS
timeFrame: Up to approximately 3 years
measure: Platelet TI, for MDS
timeFrame: Up to approximately 3 years
measure: DOR, for MDS
timeFrame: Up to approximately 3 years
measure: Progression Free Survival (PFS), for MDS
timeFrame: Up to approximately 3 years
measure: OS, for MDS
timeFrame: Up to approximately 3 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham - Main /ID# 227071
state: Alabama
city: Louisville
country: United States
facility: Norton Cancer Institute - St Matthews /ID# 228378
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital /ID# 227273
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center /ID# 231083
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan /ID# 227030
state: Michigan
city: Philadelphia
country: United States
facility: University of Pennsylvania /ID# 227024
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Ctr /ID# 228048
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center at Texas Medical Center /ID# 227019
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health /ID# 227363
state: Virginia
city: Liverpool
country: Australia
facility: Liverpool Hospital /ID# 227723
state: New South Wales
city: Heidelberg
country: Australia
facility: Austin Health /ID# 227717
state: Victoria
city: Duesseldorf
country: Germany
facility: Marien Hospital Duesseldorf /ID# 227751
state: Nordrhein-Westfalen
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig /ID# 227750
state: Sachsen
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 227749
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 227748
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center /ID# 227389
state: Tel-Aviv
city: Tel Aviv-Yafo
country: Israel
facility: Tel Aviv Sourasky Medical Center /ID# 227387
state: Tel-Aviv
city: Jerusalem
country: Israel
facility: Hadassah Medical Center-Hebrew University /ID# 227275
state: Yerushalayim
city: Petakh Tikva
country: Israel
facility: Rabin Medical Center /ID# 227738
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas /ID# 226948
state: Milano
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna /ID# 226950
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda /ID# 226952
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East /ID# 232498
state: Chiba
city: Yoshida-gun
country: Japan
facility: University of Fukui Hospital /ID# 232466
state: Fukui
city: Fukuoka-shi
country: Japan
facility: Kyushu University Hospital /ID# 232564
state: Fukuoka
city: Yamagata-shi
country: Japan
facility: Yamagata University Hospital /ID# 232451
state: Yamagata
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona /ID# 227772
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz /ID# 227771
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria /ID# 227770
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: