Study to Evaluate Adverse Events and Movement of Intravenously (IV) Infused ABBV-787 in Adult Participants With Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)
- Registration Number
- NCT06068868
- Lead Sponsor
- AbbVie
- Brief Summary
Acute myeloid leukemia (AML) is the second most common type of leukemia diagnosed in adults and children, but most cases occur in adults. This study is to evaluate how safe ABBV-787 is and how it moves within the body in adult participants with relapsed/refractory (R/R) acute myeloid leukemia (AML). Adverse events and maximum tolerated dose (MTD) of ABBV-787 will be assessed.
ABBV-787 is an investigational drug being developed for the treatment of AML. Participants will receive ABBV-787 in escalating doses until the maximum tolerated dose (MTD) is determined. Approximately 60 adult participants with a diagnosis of AML will be enrolled worldwide.
Participants will receive intravenous (IV) infusions of ABBV-787 during the approximately 3 year duration a participant is followed.
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 36
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Laboratory Criteria matching those outlined in the protocol.
- QT interval corrected for heart rate (QTc) <= 470 msec using Fridericia's correction, and no other clinically significant cardiac abnormalities.
- Documented diagnosis of non-promyelocytic acute myeloid leukemia (AML), per 2022 European Leukemia Net (ELN) criteria.
- Participants with relapsed/refractory (R/R) acute myeloid leukemia (AML) who have been treated with up to 3 prior lines of therapy and are refractory to or intolerant of all established AML therapies that are known to clearly provide clinical benefit at the judgement of the investigator.
- Must have a white blood cell (WBC) count < 25 × 10^9 /L prior to initiation of study drug (Note: Hydroxyurea or leukapheresis is permitted to meet this criterion and for use through Cycle 3 to control for hyperleukocytosis.).
- Have received a CD33-targeting therapy within 3 months prior to the first dose of ABBV-787.
- Stem cell transplant within 3 months prior to first dose of study drug.
- Have received anticancer therapy including chemotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within 14 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of ABBV-787.
- History of documented pneumonitis that required treatment with systemic steroids within the last 6 months, nor any evidence of active pneumonitis.
- Unresolved toxicity of Grade >= 2 from prior anticancer therapy, or to levels dictated in the eligibility criteria, with the exception of alopecia.
- Known active severe or poorly controlled acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ABBV-787 ABBV-787 Participants will receive increasing doses of ABBV-787 until the maximum tolerated dose (MTD) during the 3 year treatment period.
- Primary Outcome Measures
Name Time Method Number of Participants with Adverse Events (AE) Up to Approximately 3 Years An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Maximum Tolerated Dose (MTD) Based on Dose-Limiting Toxicities (DLT) Up to approximately 28 Days 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.
- Secondary Outcome Measures
Name Time Method Area Under the Plasma Concentration-time Curve (AUC) of ABBV-787 Up to Approximately 1 Year AUC of ABBV-787.
Maximum Observed Concentration (Cmax) of ABBV-787 Up to Approximately 1 Year Cmax of ABBV-787.
Time to Cmax (Tmax) of ABBV-787 Up to Approximately 1 Year Tmax of ABBV-787.
Half-life (t1/2) of ABBV-787 Up to Approximately 1 Year t1/2 of ABBV-787.
Total Antibody Concentration Up to Approximately 1 Year Total antibody concentration
Plasma Concentrations of Unconjugated Bromodomain and Extra-terminal Domain (BET) Degrader Payload Up to Approximately 1 Year Plasma concentrations of unconjugated BET degrader payload.
Antidrug Antibody (ADA) Up to Approximately 1 Year Incidence and concentration of anti-drug antibodies.
Neutralizing Antibody (nAb) Up to Approximately 1 Year Incidence and concentration of neutralizing antibodies.
Percentage of Participants Achieving Complete Remission (CR) Up to Approximately 1 Year CR is assessed by the European Leukemia Net (ELN). ELN defines refractory disease as the inability to attain complete remission (CR) or CR with incomplete hematologic recovery (CRi) after two courses of intensive induction treatment.
Rate of Participants Achieving Partial Remission (PR) Up to Approximately 1 Year PR is defined as the percentage of participants with PR per ELN 2022.
Number of Participants proceeding to hematopoietic stem cell transplant (HSCT) Up to Approximately 3 Years Number of participants proceeding to HSCT
Rate of Participants Achieving CR with partial hematologic recovery (CRh) Up to Approximately 1 Year Percentage of participants achieving CRh per ELN 2022.
Rate of Participants Achieving Composite CR (CR, CRh, or CRi) Up to Approximately 1 Year Composite CR is defined as the percentage of participants with composite CR per ELN 2022.
Duration of Response (DOR) Up to Approximately 1 Year DOR is defined for participants with CR, CRh, CRi, or PR as the time from the participant's initial response of CR, CRh, CRi, or PR per investigator review according to ELN 2022 criteria to disease progression or death of any cause, whichever occurs earlier.
Rate of Participants Achieving CR with incomplete hematologic recovery (CRi) Up to Approximately 1 Year Percentage of participants achieving CRi per ELN 2022.
Event-free Survival (EFS) Up to Approximately 3 Years EFS is defined as the time from the date of the first study treatment to the date of treatment failure, or hematologic relapse from either CR, CRh, or CRi, or death from any cause, whichever occurs earlier.
Relapse free survival (RFS) Up to Approximately 3 Years RFS is defined for participants achieving CR, CRh, or CRi as time from the date of achievement of remission (CR, CRh, or CRi) until the date of hematologic relapse or death from any cause.
Overall survival (OS) Up to Approximately 3 Years OS is defined as time from first study treatment to death from any cause.
Trial Locations
- Locations (24)
University of Maryland, Baltimore /ID# 253726
🇺🇸Baltimore, Maryland, United States
Monash Health - Monash Medical Centre /ID# 253841
🇦🇺Clayton, Victoria, Australia
City of Hope /ID# 253727
🇺🇸Duarte, California, United States
University of California Davis Health /ID# 252723
🇺🇸Sacramento, California, United States
Yale University School of Medicine /ID# 252724
🇺🇸New Haven, Connecticut, United States
Northwestern Memorial Hospital /ID# 252800
🇺🇸Chicago, Illinois, United States
University of Chicago Medical /ID# 252764
🇺🇸Chicago, Illinois, United States
Cancer & Hematology Centers /ID# 252803
🇺🇸Grand Rapids, Michigan, United States
Memorial Sloan Kettering Cancer Center-Koch Center /ID# 252515
🇺🇸New York, New York, United States
Weill Cornell Medical College /ID# 252516
🇺🇸New York, New York, United States
University of Pennsylvania /ID# 252789
🇺🇸Philadelphia, Pennsylvania, United States
St. David's South Austin Medical Center /ID# 252790
🇺🇸Austin, Texas, United States
MD Anderson Cancer Center /ID# 252514
🇺🇸Houston, Texas, United States
Fred Hutchinson Cancer Research Center /ID# 253730
🇺🇸Seattle, Washington, United States
Wisconsin Medical Center /ID# 252513
🇺🇸Milwaukee, Wisconsin, United States
Peter MacCallum Cancer Ctr /ID# 252517
🇦🇺Melbourne, Victoria, Australia
The Chaim Sheba Medical Center /ID# 252913
🇮🇱Ramat Gan, Tel-Aviv, Israel
Tel Aviv Sourasky Medical Center /ID# 252914
🇮🇱Tel Aviv, Tel-Aviv, Israel
Hadassah Medical Center-Hebrew University /ID# 252915
🇮🇱Jerusalem, Israel
National Cancer Center Hospital East /ID# 252519
🇯🇵Kashiwa-shi, Chiba, Japan
Yamagata University Hospital /ID# 254105
🇯🇵Yamagata-shi, Yamagata, Japan
Seoul National University Hospital /ID# 252916
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Asan Medical Center /ID# 253955
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Yonsei University Health System Severance Hospital /ID# 253956
🇰🇷Seoul, Korea, Republic of