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

NCT01328626 | Completed Phase 1 FDA Drug

• 1 other identifier: M12-175
• Study Type: interventional
• Target: 222
• Locations: 2 countries
• Sites: 10

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.

Conditions

Chronic Lymphocytic Leukemia; Non-Hodgkin Lymphoma

Keywords

Safety; Maximum Tolerated Dose; Pharmacokinetics; ABT-199; Preliminary Efficacy; Cancer; Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (5)

• 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.

  Lead-in period (2-5 weeks) plus 3 weeks of study drug administration at the designated cohort dose (continuous dosing)

• Number of subjects with adverse events

  First 16 weeks of study drug administration and every 4 weeks thereafter (continuous dosing for an anticipated maximum duration of 9 months)

• 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

  Up to Week 24 for ABT-199

• 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

  Up to Week 24 for ABT-199

• 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

  Up to Week 24 for ABT-199

Secondary Outcomes (5)

• Food Effect - Cmax

  Approximately 3 days

• Preliminary efficacy assessment

  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)

• Minimal residual disease collection (MRD)

  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).

• Food Effect - Tmax

  Approximately 3 days

• Food Effect - AUC

  Approximately 3 days

Study Arms (2)

Arm A (CLL/SLL subjects)

EXPERIMENTAL

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) subjects

Drug: ABT-199

Arm B (NHL subjects)

EXPERIMENTAL

Non-Hodgkin lymphoma (NHL) subjects

Drug: ABT-199

Interventions

ABT-199 DRUG

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.

Arm A (CLL/SLL subjects); Arm B (NHL subjects)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• AbbVie: lead
• Genentech, Inc.: collaborator

Study Sites (10)

University of Arizona Cancer Center - North Campus /ID# 52902

Tucson, Arizona, 85719-1478, United States

Location

Ucsd /Id# 48325

La Jolla, California, 92093, United States

Location

Dana-Farber Cancer Institute /ID# 48324

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center /ID# 56810

New York, New York, 10065-6007, United States

Location

University of Texas MD Anderson Cancer Center /ID# 48326

Houston, Texas, 77030, United States

Location

Swedish Medical Center /ID# 135853

Seattle, Washington, 98104, United States

Location

Fred Hutchinson Cancer Research /ID# 52882

Seattle, Washington, 98109, United States

Location

Univ of Wisconsin Hosp/Clinics /ID# 56811

Madison, Wisconsin, 53792-0001, United States

Location

Peter MacCallum Cancer Ctr /ID# 48323

Melbourne, Victoria, 3000, Australia

Location

Royal Melbourne Hospital /ID# 48322

Parkville, Victoria, 3050, Australia

Location

Related Publications (4)

• Davids MS, Roberts AW, Seymour JF, Pagel JM, Kahl BS, Wierda WG, Puvvada S, Kipps TJ, Anderson MA, Salem AH, Dunbar M, Zhu M, Peale F, Ross JA, Gressick L, Desai M, Kim SY, Verdugo M, Humerickhouse RA, Gordon GB, Gerecitano JF. Phase I First-in-Human Study of Venetoclax in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma. J Clin Oncol. 2017 Mar 10;35(8):826-833. doi: 10.1200/JCO.2016.70.4320. Epub 2017 Jan 17.

  PMID: 28095146 BACKGROUND

• Davids MS, Roberts AW, Kenkre VP, Wierda WG, Kumar A, Kipps TJ, Boyer M, Salem AH, Pesko JC, Arzt JA, Mantas M, Kim SY, Seymour JF. Long-term Follow-up of Patients with Relapsed or Refractory Non-Hodgkin Lymphoma Treated with Venetoclax in a Phase I, First-in-Human Study. Clin Cancer Res. 2021 Sep 1;27(17):4690-4695. doi: 10.1158/1078-0432.CCR-20-4842. Epub 2021 Jun 3.

  PMID: 34083230 DERIVED

• Roberts AW, Ma S, Kipps TJ, Coutre SE, Davids MS, Eichhorst B, Hallek M, Byrd JC, Humphrey K, Zhou L, Chyla B, Nielsen J, Potluri J, Kim SY, Verdugo M, Stilgenbauer S, Wierda WG, Seymour JF. Efficacy of venetoclax in relapsed chronic lymphocytic leukemia is influenced by disease and response variables. Blood. 2019 Jul 11;134(2):111-122. doi: 10.1182/blood.2018882555. Epub 2019 Apr 25.

  PMID: 31023700 DERIVED

• Roberts AW, Davids MS, Pagel JM, Kahl BS, Puvvada SD, Gerecitano JF, Kipps TJ, Anderson MA, Brown JR, Gressick L, Wong S, Dunbar M, Zhu M, Desai MB, Cerri E, Heitner Enschede S, Humerickhouse RA, Wierda WG, Seymour JF. Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2016 Jan 28;374(4):311-22. doi: 10.1056/NEJMoa1513257. Epub 2015 Dec 6.

  PMID: 26639348 DERIVED

Related Links

• clinical study report synopsis

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Neoplasms

Interventions

venetoclax

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma

Study Officials

• AbbVie Inc.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: April 1, 2011
• First Posted: April 5, 2011
• Study Start: May 23, 2011
• Primary Completion: May 8, 2020
• Study Completion: May 8, 2020
• Last Updated: February 23, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2); US (8)