B-All, Multiple Myeloma, Non-Hodgkins Lymphoma
Conditions
Keywords
Bruton tyrosine kinase inhibitor, Btk, B-Cell Malignancies, Mantle Cell, Multiple Myeloma, CLL, SLL, DLBCL, Follicular, Waldenstrom, B-All
Brief summary
This study is evaluating the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy acalabrutinib and ACP 319 in B-cell malignancies.
Detailed description
Part 1, Dose Escalation, is comprised of 3 dosing cohorts of 6 subjects each. Acalabrutinib dosing is fixed in all cohorts at 100 mg PO twice daily (BID). In addition to acalabrutinib, subjects in Cohort 1 will receive ACP-319, 25 mg BID; Cohort 2 will receive ACP-319, 50 mg BID: and Cohort 3 will receive ACP-319 100 mg BID. The maximum tolerated dose (MTD) of the study treatment combination will be determined by assessing dose-related toxicities (DLTs) for each cohort at the end of Cycle 1 prior to dose escalation. If there are greater than or equal to 2 DLTs in a cohort, dose escalation will not occur and the MTD will be the highest daily dose for which less than 33% of the subjects in that cohort experienced DLTs in Cycle 1. Part 2, Dose Expansion, includes 12 subjects per histology, dosing at the MTD for the combination of acalabrutinib and ACP-319 established in Part 1. Subjects will continue dosing until disease progression or unacceptable drug-related toxicity.
Interventions
DRUGAcalabrutinib
Oral
DRUGACP-319
Oral
Sponsors
AstraZeneca
Acerta Pharma BV
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Diagnosis of a b-cell malignancy as documented by medical records and with histology based on criteria established by the World Health Organization (WHO). * Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. * Agreement to use contraception during the study and for 90 days after the last dose of study drugs if sexually active and able to bear or beget children.
Exclusion criteria
* A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of study drugs, or put the study outcomes at undue risk. * Central nervous system (CNS) involvement by lymphoma/leukemia * Any therapeutic antibody within 4 weeks of first dose of study drugs. * The time from the last dose of the most recent chemotherapy or experimental therapy to the first dose of study drugs is \< 5 times the half-life of the previously administered agent(s). * ANC \< 0.5 x 10\^9/L or platelet count \< 50 x 10\^9/L unless due to disease involvement in the bone marrow. * Creatinine \> 1.5 x institutional upper limit of normal (ULN); total bilirubin \> 1.5 x ULN (unless due to Gilbert's disease); and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3.0 x ULN.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Response and Overall Response Rate | from the start of the treatment to the last evaluable disease assessment, an average of 1 year | Best response and overall response rate per the criteria investigator uses for each disease histology. Standardized response and progression criteria is based on established criteria for B-cell malignancies, including WM (Cheson 2014; Owen 2013; Hallek 2008; Bladé 1998; and Durie 2006). |
Countries
United States
Participant flow
Pre-assignment details
All data collection and Final analysis for the study has been completed. However, as we face a unique challenge in oncology studies, some patients benefiting from the medication, continue to receive treatment beyond final analysis with NO requirement for any further data collection or additional data analysis.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 Cohort 1 Part 1 Cohort 1: ACP-196 100 mg BID + ACP-319 25 mg BID continuously | 6 |
| Part 1 Cohort 2 Part 1 Cohort 2: ACP-196 100 mg BID + ACP-319 50 mg BID continuously | 6 |
| Part 1 Cohort 3 Part 1 Cohort 3: ACP-196 100 mg BID + ACP-319 100 mg BID continuously | 6 |
| Part 2 Part 2: ACP-196 100 mg BID + ACP-319 50 mg BID continuously | 22 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 1 |
| Overall Study | Death | 0 | 0 | 0 | 4 |
| Overall Study | Disease Progression | 1 | 0 | 1 | 3 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 |
| Overall Study | Study Terminated by Sponsor | 4 | 1 | 1 | 0 |
| Overall Study | Subject Started Another Cancer Therapy | 0 | 5 | 4 | 12 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Part 2 | Part 1 Cohort 3 | Part 1 Cohort 1 | Part 1 Cohort 2 |
|---|---|---|---|---|---|
| Age, Continuous | 68.3 Years STANDARD_DEVIATION 9.2 | 68.3 Years STANDARD_DEVIATION 9.2 | 62.5 Years STANDARD_DEVIATION 7.9 | 61.2 Years STANDARD_DEVIATION 7.3 | 68.0 Years STANDARD_DEVIATION 9.9 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 39 Participants | 22 Participants | 6 Participants | 6 Participants | 5 Participants |
| Race/Ethnicity, Customized Not Reported | 5 Participants | 3 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 34 Participants | 18 Participants | 5 Participants | 6 Participants | 5 Participants |
| Region of Enrollment United States | 40 Participants | 22 Participants | 6 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Female | 16 Participants | 9 Participants | 3 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 24 Participants | 13 Participants | 3 Participants | 3 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 4 / 22 |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 6 / 6 | 22 / 22 |
| serious Total, serious adverse events | 3 / 6 | 3 / 6 | 5 / 6 | 11 / 22 |
Outcome results
Primary
Best Response and Overall Response Rate
Best response and overall response rate per the criteria investigator uses for each disease histology. Standardized response and progression criteria is based on established criteria for B-cell malignancies, including WM (Cheson 2014; Owen 2013; Hallek 2008; Bladé 1998; and Durie 2006).
Time frame: from the start of the treatment to the last evaluable disease assessment, an average of 1 year
Population: All-Treated Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1 Cohort 1 | Best Response and Overall Response Rate | CR | 33.3 percentage of participants |
| Part 1 Cohort 1 | Best Response and Overall Response Rate | Missing | 0 percentage of participants |
| Part 1 Cohort 1 | Best Response and Overall Response Rate | ORR (CR+VGPR+PR) | 83.3 percentage of participants |
| Part 1 Cohort 1 | Best Response and Overall Response Rate | VGPR | 16.7 percentage of participants |
| Part 1 Cohort 1 | Best Response and Overall Response Rate | PD | 0 percentage of participants |
| Part 1 Cohort 1 | Best Response and Overall Response Rate | PR | 33.3 percentage of participants |
| Part 1 Cohort 1 | Best Response and Overall Response Rate | SD | 16.7 percentage of participants |
| Part 1 Cohort 2 | Best Response and Overall Response Rate | PD | 33.3 percentage of participants |
| Part 1 Cohort 2 | Best Response and Overall Response Rate | Missing | 0 percentage of participants |
| Part 1 Cohort 2 | Best Response and Overall Response Rate | PR | 50 percentage of participants |
| Part 1 Cohort 2 | Best Response and Overall Response Rate | CR | 0 percentage of participants |
| Part 1 Cohort 2 | Best Response and Overall Response Rate | VGPR | 0 percentage of participants |
| Part 1 Cohort 2 | Best Response and Overall Response Rate | SD | 16.7 percentage of participants |
| Part 1 Cohort 2 | Best Response and Overall Response Rate | ORR (CR+VGPR+PR) | 50 percentage of participants |
| Part 1 Cohort 3 | Best Response and Overall Response Rate | CR | 16.7 percentage of participants |
| Part 1 Cohort 3 | Best Response and Overall Response Rate | Missing | 33.3 percentage of participants |
| Part 1 Cohort 3 | Best Response and Overall Response Rate | ORR (CR+VGPR+PR) | 66.7 percentage of participants |
| Part 1 Cohort 3 | Best Response and Overall Response Rate | PD | 0 percentage of participants |
| Part 1 Cohort 3 | Best Response and Overall Response Rate | PR | 50 percentage of participants |
| Part 1 Cohort 3 | Best Response and Overall Response Rate | SD | 0 percentage of participants |
| Part 1 Cohort 3 | Best Response and Overall Response Rate | VGPR | 0 percentage of participants |
| Part 2 | Best Response and Overall Response Rate | ORR (CR+VGPR+PR) | 40.9 percentage of participants |
| Part 2 | Best Response and Overall Response Rate | PR | 22.7 percentage of participants |
| Part 2 | Best Response and Overall Response Rate | Missing | 0 percentage of participants |
| Part 2 | Best Response and Overall Response Rate | CR | 18.2 percentage of participants |
| Part 2 | Best Response and Overall Response Rate | VGPR | 0 percentage of participants |
| Part 2 | Best Response and Overall Response Rate | SD | 4.5 percentage of participants |
| Part 2 | Best Response and Overall Response Rate | PD | 36.4 percentage of participants |