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

Sponsor

AbbVie (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04912063

Collaborator

(none)

Enrollment

Locations

Arms

32.5

Anticipated Duration (Months)

2.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia (AML) Myelodysplastic Syndrome (MDS)	Drug: Lemzoparlimab Drug: Azacitidine Drug: Venetoclax	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Jun 25, 2021

Anticipated Primary Completion Date :

Mar 9, 2024

Anticipated Study Completion Date :

Mar 9, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Lemzoparlimab Intravenous (IV) Infusion Other Names: TJ011133 ABBV-IMAB-TJC4 Drug: Azacitidine Subcutaneous Injection or Intravenous (IV) Injection/Infusion Drug: Venetoclax Oral Tablet Other Names: Venclexta Venclyxto ABT-199 GDC-0199
Experimental: 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).	Drug: Lemzoparlimab Intravenous (IV) Infusion Other Names: TJ011133 ABBV-IMAB-TJC4 Drug: Azacitidine Subcutaneous Injection or Intravenous (IV) Injection/Infusion Drug: Venetoclax Oral Tablet Other Names: Venclexta Venclyxto ABT-199 GDC-0199
Experimental: Lemzoparlimab + Azacitidine in MDS (Escalation) Lemzoparlimab (TJ011133) co-administered with azacitidine in escalated doses in participants with treatment-naïve higher-risk myelodysplastic syndrome (MDS).	Drug: Lemzoparlimab Intravenous (IV) Infusion Other Names: TJ011133 ABBV-IMAB-TJC4 Drug: Azacitidine Subcutaneous Injection or Intravenous (IV) Injection/Infusion
Experimental: 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.	Drug: Lemzoparlimab Intravenous (IV) Infusion Other Names: TJ011133 ABBV-IMAB-TJC4 Drug: Azacitidine Subcutaneous Injection or Intravenous (IV) Injection/Infusion Drug: Venetoclax Oral Tablet Other Names: Venclexta Venclyxto ABT-199 GDC-0199
Experimental: 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).	Drug: Lemzoparlimab Intravenous (IV) Infusion Other Names: TJ011133 ABBV-IMAB-TJC4 Drug: Azacitidine Subcutaneous Injection or Intravenous (IV) Injection/Infusion Drug: Venetoclax Oral Tablet Other Names: Venclexta Venclyxto ABT-199 GDC-0199
Experimental: 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.	Drug: Lemzoparlimab Intravenous (IV) Infusion Other Names: TJ011133 ABBV-IMAB-TJC4
Experimental: Lemzoparlimab Monotherapy in MDS (Japan Only Escalation) Lemzoparlimab (TJ011133) administered in escalated doses in participants with treatment-naïve higher-risk myelodysplastic syndrome (MDS).	Drug: Lemzoparlimab Intravenous (IV) Infusion Other Names: TJ011133 ABBV-IMAB-TJC4

Outcome Measures

Primary Outcome Measures

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 [Up to 30 days after first dose of study drug]
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.
DLTs of Lemzoparlimab (TJ011133) When Co-administered With Azacitidine With or Without Venetoclax in Participants With Treatment-Naïve Higher-Risk Myelodysplastic Syndrome (MDS) [Up to 30 days after first dose of study drug]
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.
Dose Limiting Toxicities (DLTs) of Lemzoparlimab (TJ011133) as a Monotherapy in Japanese Participants with Relapsed/Refractory (R/R) AML [Up to 30 days after first dose of study drug]
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.
DLTs of Lemzoparlimab (TJ011133) as a Monotherapy in Japanese Participants with R/R MDS [Up to 30 days after first dose of study drug]
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.

Secondary Outcome Measures

Best Overall Response of Complete Remission (CR) for AML [Up to approximately 3 years]
Best overall response of complete remission (CR), defined as achieving CR according to modified international working group (IWG) 2003 criteria for AML.
Best Overall Response of Composite CR (CRc) for AML [Up to approximately 3 years]
Best overall response of composite CR (CRc), [CR or CR with incomplete blood count recovery (CRi)] according to modified IWG 2003 criteria for AML.
Best Overall Response of CR or Complete Remission With Partial Hematologic Recovery (CRh) for AML [Up to approximately 3 years]
Best overall response of CR or CRh, defined according to modified IWG 2003 criteria for AML.
Duration of Response (DOR) for AML [Up to approximately 3 years]
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.
Event-Free Survival (EFS) for AML [Up to approximately 3 years]
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.
Overall Survival (OS ) for AML [Up to approximately 3 years]
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.
Best Overall Response of CR, for MDS [Up to approximately 3 years]
Best overall response of CR per the modified IWG 2006 criteria for MDS.
Best Overall Response of Marrow-Complete Remission (mCR), for MDS [Up to approximately 3 years]
Best overall response of marrow-complete remission (mCR), per the modified IWG 2006 criteria for MDS.
Best Overall Response of CR or PR for MDS [Up to approximately 3 years]
Best overall response of CR or PR, per the modified IWG 2006 criteria for MDS.
Best Overall Response of CR or PR or mCR, for MDS [Up to approximately 3 years]
Best overall response of CR or PR or mCR, per the modified IWG 2006 criteria for MDS.
Hematologic Improvement (HI), for MDS [Up to approximately 3 years]
Hematologic improvement (HI), defined as a participant achieving erythroid/platelet/neutrophil responses.
Red Blood Cell Transfusion Independence (TI), for MDS [Up to approximately 3 years]
Red blood cell transfusion independence (TI), defined as a participant who is transfusion dependent at baseline achieved TI post-baseline.
Platelet TI, for MDS [Up to approximately 3 years]
Platelet TI, defined as a participant who is transfusion dependent at baseline achieved TI post-baseline.
DOR, for MDS [Up to approximately 3 years]
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.
Progression Free Survival (PFS), for MDS [Up to approximately 3 years]
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.
OS, for MDS [Up to approximately 3 years]
OS, defined as the time from the date of the first dose of any study drug to death from any cause.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham - Main /ID# 227071	Birmingham	Alabama	United States	35233
2	University of California, Los Angeles /ID# 227752	Los Angeles	California	United States	90095
3	The University of Chicago Medical Center /ID# 228689	Chicago	Illinois	United States	60637-1443
4	Norton Cancer Institute - St Matthews /ID# 228378	Louisville	Kentucky	United States	40207
5	Massachusetts General Hospital /ID# 227273	Boston	Massachusetts	United States	02114
6	Beth Israel Deaconess Medical Center /ID# 231083	Boston	Massachusetts	United States	02215-5400
7	University of Michigan /ID# 227030	Ann Arbor	Michigan	United States	48109
8	Oregon Health and Science University /ID# 227121	Portland	Oregon	United States	97239
9	University of Pennsylvania /ID# 227024	Philadelphia	Pennsylvania	United States	19104
10	UPMC Hillman Cancer Ctr /ID# 228048	Pittsburgh	Pennsylvania	United States	15232
11	MD Anderson Cancer Center at Texas Medical Center /ID# 227019	Houston	Texas	United States	77030-4000
12	University of Virginia Health /ID# 227363	Charlottesville	Virginia	United States	22908
13	Liverpool Hospital /ID# 227723	Liverpool	New South Wales	Australia	2170
14	Austin Health /ID# 227717	Heidelberg	Victoria	Australia	3084
15	Tom Baker Cancer Centre /ID# 227863	Calgary	Alberta	Canada	T2N 4N2
16	Juravinski Cancer Centre /ID# 227867	Hamilton	Ontario	Canada	L8V 1C3
17	Marien Hospital Duesseldorf /ID# 227751	Duesseldorf	Nordrhein-Westfalen	Germany	40479
18	Universitaetsklinikum Leipzig /ID# 227750	Leipzig	Sachsen	Germany	04103
19	Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 227749	Dresden		Germany	01307
20	Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 227748	Hamburg		Germany	20246
21	The Chaim Sheba Medical Center /ID# 227389	Ramat Gan	Tel-Aviv	Israel	5265601
22	Tel Aviv Sourasky Medical Center /ID# 227387	Tel Aviv-Yafo	Tel-Aviv	Israel	6423906
23	Hadassah Medical Center-Hebrew University /ID# 227275	Jerusalem		Israel	91120
24	Rabin Medical Center /ID# 227738	Petakh Tikva		Israel	4941492
25	Istituto Clinico Humanitas /ID# 226948	Rozzano	Milano	Italy	20089
26	IRCCS Azienda Ospedaliero-Universitaria di Bologna /ID# 226950	Bologna		Italy	40138
27	ASST Grande Ospedale Metropolitano Niguarda /ID# 226952	Milano		Italy	20162
28	National Cancer Center Hospital East /ID# 232498	Kashiwa-shi	Chiba	Japan	277-8577
29	University of Fukui Hospital /ID# 232466	Yoshida-gun	Fukui	Japan	910-1193
30	Kyushu University Hospital /ID# 232564	Fukuoka-shi	Fukuoka	Japan	812-8582
31	Yamagata University Hospital /ID# 232451	Yamagata-shi	Yamagata	Japan	990-9585
32	Hospital Clinic de Barcelona /ID# 227772	Barcelona		Spain	08036
33	Hospital Universitario Fundacion Jimenez Diaz /ID# 227771	Madrid		Spain	28040
34	Hospital Universitario Virgen de la Victoria /ID# 227770	Malaga		Spain	29010
35	King's College Hospital NHS Foundation Trust /ID# 229572	London		United Kingdom	SE5 9RS
36	The Christie Hospital /ID# 229578	Manchester		United Kingdom	M20 4BX