The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01328626




Registration number
NCT01328626
Ethics application status
Date submitted
1/04/2011
Date registered
5/04/2011
Date last updated
18/05/2020

Titles & IDs
Public title
A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABT-199 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia and Non-Hodgkin Lymphoma
Scientific title
A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABT-199 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia and Non-Hodgkin Lymphoma
Secondary ID [1] 0 0
M12-175
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Lymphocytic Leukemia 0 0
Non-Hodgkin Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - ABT-199

Experimental: Arm A (CLL/SLL subjects) - Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) subjects

Experimental: Arm B (NHL subjects) - Non-Hodgkin lymphoma (NHL) subjects


Treatment: Drugs: ABT-199
Arm A (Cohorts 1-8) and Arm B (Cohort 1-6): Subjects in dose escalation phase will receive 1 dose of ABT-199, followed by 6 days off drug, followed by continuous once daily dosing with ABT-199. Arm B (Cohorts 7+): Subjects in dose escalation phase will receive continuous once daily dosing with ABT-199. Arm A and Arm B: Subjects in expanded safety cohort will receive continuous once daily dosing with ABT-199.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Determination of dose limiting toxicity (DLT), maximum tolerated dose (MTD), recommended phase two dose (RPTD), and lead-in period regimen - Protocol-defined events, which can not be attributed by the investigator to a clearly identifiable cause such as tumor progression, underlying illness, concurrent illness, or concomitant medication, will be considered a DLT. Dose limiting toxicities of tumor lysis syndrome observed during the lead-in period will be attributed to the lead-in period.
Timepoint [1] 0 0
Lead-in period (2-5 weeks) plus 3 weeks of study drug administration at the designated cohort dose (continuous dosing)
Primary outcome [2] 0 0
Number of subjects with adverse events
Timepoint [2] 0 0
First 16 weeks of study drug administration and every 4 weeks thereafter (continuous dosing for an anticipated maximum duration of 9 months)
Primary outcome [3] 0 0
Determination of plasma peak concentration (Cmax) of ABT-199 - Blood and urine samples for pharmacokinetic analysis of ABT-199 will be collected at designated time points
Timepoint [3] 0 0
Up to Week 24 for ABT-199
Primary outcome [4] 0 0
Determination of trough concentration (Ctrough) of ABT-199 - Blood and urine samples for pharmacokinetic analysis of ABT-199 will be collected at designated time points
Timepoint [4] 0 0
Up to Week 24 for ABT-199
Primary outcome [5] 0 0
Determination of area under the concentration versus time curve (AUC) of ABT-199 - Blood and urine samples for pharmacokinetic analysis of ABT-199 will be collected at designated time points
Timepoint [5] 0 0
Up to Week 24 for ABT-199
Secondary outcome [1] 0 0
Food Effect - Cmax - Pharmacokinetic (PK) parameter Cmax (maximum plasma concentration of ABT-199) between each diet (ABT-199 under fasting versus low-fat, and fasting versus high-fat conditions (Cohorts 1-6 in Arm B subjects only)
Timepoint [1] 0 0
Approximately 3 days
Secondary outcome [2] 0 0
Preliminary efficacy assessment - Tumor response or clinical disease progression
Timepoint [2] 0 0
Starting Week 4 for clinical disease progression and Week 6 for tumor response; and every 4 weeks thereafter (continuous dosing for an anticipated maximum duration of 9 months)
Secondary outcome [3] 0 0
Minimal residual disease collection (MRD) - MRD assessed in the peripheral blood and/or bone marrow (BM) either by four color flow cytometry or ASO-PCR, will be measured in CLL subjects achieving CR/CRi.
Timepoint [3] 0 0
At least 2 months after the CR, CRi criteria for tumor response are first met. Every 12 weeks thereafter, until MRD negativity has been achieved (in peripheral blood).
Secondary outcome [4] 0 0
Food Effect - Tmax - Pharmacokinetic (PK) parameter Tmax (time to reach maximum plasma concentration of ABT-199) between each diet (ABT-199 under fasting versus low-fat, and fasting versus high-fat conditions (Cohorts 1-6 in Arm B subjects only)
Timepoint [4] 0 0
Approximately 3 days
Secondary outcome [5] 0 0
Food Effect - AUC - Pharmacokinetic (PK) parameter AUC (area under the concentration-time curve from time zero to hour 24 of ABT-199) between each diet (ABT-199 under fasting versus low-fat, and fasting versus high-fat conditions (Cohorts 1-6 in Arm B subjects only)
Timepoint [5] 0 0
Approximately 3 days

Eligibility
Key inclusion criteria
- Subject must have either:

- (Arm A) relapsed or refractory CLL/SLL and require treatment in the opinion of
the Investigator. Subject must have relapsed following or be refractory to
standard treatments such as fludarabine based regimens (F, FC, FR, FCR) or
alkylator (chlorambucil, bendamustine) based regimens. In addition, there are no
other curative options, and the subject has exhausted options that would be
considered standard of care, or

- (Arm B) relapsed or refractory NHL and require treatment in the opinion of the
Investigator. Subject must have histologically documented diagnosis of NHL as
defined in the World Health Organization classification scheme, except as noted
in the exclusion criteria. Subject must have relapsed following or be refractory
to standard treatments such as R-CHOP, R-CVP, or fludarabine based regimens. In
addition, there are no other curative options, and the subject has exhausted
options that would be considered standard of care. Subjects with other
lymphoproliferative diseases can be considered in consultation with the Abbott
medical monitor.

- Subject has an Eastern Cooperative Oncology Group (ECOG) performance score less than
or equal to 1.

- Subject must have adequate bone marrow independent of growth factor support per local
laboratory reference range at Screening.

- Subject must have adequate coagulation, renal, and hepatic function, per laboratory
reference range at Screening.
Minimum age
18 Years
Maximum age
99 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- CLL subject has undergone an allogeneic or autologous stem cell transplant or NHL
subject has undergone an allogeneic stem cell transplant or has been diagnosed with
Post-Transplant Lymphoproliferative Disease, Burkitt's lymphoma, Burkitt-like
lymphoma, or lymphoblastic lymphoma/leukemia.

- Subject has tested positive for HIV.

- Subject has a cardiovascular disability status of New York Heart Association Class
greater or equal to 2. Class 2 is defined as cardiac disease in which patients are
comfortable at rest but ordinary physical activity, results in fatigue, palpitations,
dyspnea or anginal pain.

- Subject has a significant history of renal, neurologic, psychiatric, pulmonary,
endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that in the
opinion of the Investigator would adversely affect his/her participating in this
study.

- Subject has received a monoclonal antibody for anti-neoplastic intent within 8 weeks
prior to the first dose of study drug.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Ctr /ID# 48323 - Melbourne
Recruitment hospital [2] 0 0
Royal Melbourne Hospital /ID# 48322 - Parkville
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
United States of America
State/province [6] 0 0
Washington
Country [7] 0 0
United States of America
State/province [7] 0 0
Wisconsin

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AbbVie
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Genentech, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 1, open-label, multicenter study evaluating the safety and PK profile of
ABT-199 under a once daily dosing schedule. Two arms will be implemented for dose escalation:
Arm A, CLL/SLL subjects and Arm B, NHL subjects. Arm A is designed to enroll approximately
116 subjects with relapsed or refractory CLL or SLL and Arm B is designed to enroll
approximately 95 subjects with relapsed or refractory NHL. Fifty-six subjects were enrolled
in Arm A and approximately 55 subjects will be enrolled in Arm B during the dose escalation
portion of the study, with the objective of defining dose limiting toxicities (DLTs) and the
MTD. Once the MTD is declared for the arm, approximately 60 additional CLL/SLL subjects in
Arm A and approximately 20 additional DLBCL subjects and 20 additional follicular lymphoma
subjects in Arm B will be enrolled in an expanded safety portion of the study at the
recommended phase 2 dose (RPTD) and schedule.
Trial website
https://clinicaltrials.gov/show/NCT01328626
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
AbbVie Inc.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications