Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries. The purpose of this study is to assess how well ABBV-453 works adult participants with relapsed/refractory (R/R) untreated CLL/small lymphocytic lymphoma (SLL). Adverse events, pharmacokinetics, and change in disease activity will be assessed. ABBV-453 is an investigational drug for the treatment of CLL and SLL. Participants will be enrolled with a specific target dose and receive obinutuzumab during the debulking period followed escalating doses of ABBV-453, until the appropriate target dose is achieved. Approximately 60 adult participants with previously R/R CLL/SLL will be enrolled in the study in approximately 40 sites across the world. Participants will receive intravenous (IV) obinutuzumab as part of the debulking period, followed by escalating doses of oral ABBV-453 until the appropriate target dose is achieved. The estimated study duration is 3 years. 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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
4
Intravenous Infusion
Oral; Tablet
City of Hope /ID# 253904
Duarte, California, United States
City of Hope - Orange County Lennar Foundation Cancer Center /ID# 267158
Irvine, California, United States
Intermountain Health St Vincent Regional Hospital - Cancer Centers of Montana /ID# 264622
Billings, Montana, United States
Atrium Health Levine Cancer Institute /ID# 265136
Charlotte, North Carolina, United States
Duplicate_Duke Cancer Center /ID# 258707
Durham, North Carolina, United States
MD Anderson Cancer Center /ID# 253713
Houston, Texas, United States
Royal Prince Alfred Hospital /ID# 263129
Sydney, New South Wales, Australia
Gold coast University Hospital /ID# 255785
Southport, Queensland, Australia
Austin Health /ID# 256776
Heidelberg, Victoria, Australia
Royal Perth Hospital /ID# 256464
Perth, Western Australia, Australia
...and 11 more locations
Percentage of Participants With Adverse Events (AEs)
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.
Time frame: Up to 3 Years
Maximum Administered Dose (MAD) of ABBV-453
MAD is defined as the highest administered dose if no maximum tolerated dose (MTD) is determined.
Time frame: Up to 18 Months
Maximum Tolerated Dose (MTD) of ABBV-453
MTD is defined as the highest dose administered that does not result in a final determination of de-escalate at that dose level.
Time frame: Up to 18 Months
Maximum Observed Plasma Concentration (Cmax) of ABBV-453
Cmax is defined as the maximum observed plasma/serum concentration of ABBV-453.
Time frame: Up to 30 Months
Time to Maximum Observed Concentration (Tmax) of ABBV-453
Tmax is defined as the time to maximum observed concentration of ABBV-453.
Time frame: Up to 30 Months
Area Under the Plasma/Serum Concentration Versus Time Curve (AUC) of ABBV-453
Area under the plasma/serum concentration versus time curve (AUC) of ABBV-453.
Time frame: Up to 30 Months
Overall Response Rate (ORR)
Percentage of participants achieving a complete response (CR), complete response with incomplete count recovery (CRi), partial response (PR), or nodular partial response (nPR) using disease-specific criteria per the International Workshop on Chronic Lymphocytic Leukemia (iwCLL, 2018).
Time frame: Up to 3 Years
Duration of Response (DOR) for Participants with PR/nPR or Better
DOR is defined as the time between the initial PR or better response assessment per Investigator according to iwCLL criteria to the time of progressive disease (PD) or death of any cause, whichever occurs earlier.
Time frame: Up to 3 Years
Complete response rate (CRR)
CRR is defined as the percentage of participants with a best overall response (BOR) of CR or CRi per Investigator review according to iwCLL for participants with relapsed or refractory CLL/SLL, regardless of reasons for study drug discontinuation, and prior to start of subsequent anti-cancer therapies in the participants receiving at least one dose of ABBV-453 monotherapy.
Time frame: Up to 3 Years
Duration of Complete Response (DOCR)
DOCR is defined as the time between the initial CR/CRi response assessment per Investigator according to iwCLL criteria to the time of PD or death of any cause, whichever occurs earlier.
Time frame: Up to 3 Years
Percentage of Participants Achieving an Minimal Residual Disease (MRD) Negativity Among Participants Achieving a PR, nPR, CR, or CRi
MRD response is defined as \< 1 cell in 10,000 leukocytes (\< 10\^-4).
Time frame: Up to 3 Years
Progression-free survival (PFS)
PFS is defined as time from first study treatment to a documented PD (based on iwCLL criteria) as determined by the Investigator, or death due to any cause, whichever occurs earlier.
Time frame: Up to 3 Years
Overall survival (OS)
OS is defined as the time from the first date of study treatment until date of death due to any cause.
Time frame: Up to 3 Years
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