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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

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ClinicalTrials.gov Identifier: NCT01328626
Recruitment Status : Active, not recruiting
First Posted : April 5, 2011
Last Update Posted : May 10, 2018
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
AbbVie

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.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Non-Hodgkin Lymphoma Drug: ABT-199 Phase 1

Detailed Description:
Interventional Study Design - Primary Purpose: Determination of safety and tolerability.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 221 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : July 4, 2011
Estimated Primary Completion Date : November 14, 2019
Estimated Study Completion Date : November 14, 2019


Arm Intervention/treatment
Experimental: Arm A (CLL/SLL subjects)
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) subjects
Drug: 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.
Experimental: Arm B (NHL subjects)
Non-Hodgkin lymphoma (NHL) subjects
Drug: 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.



Primary Outcome Measures :
  1. Determination of dose limiting toxicity (DLT), maximum tolerated dose (MTD), recommended phase two dose (RPTD), and lead-in period regimen [ Time Frame: Lead-in period (2-5 weeks) plus 3 weeks of study drug administration at the designated cohort dose (continuous dosing) ]
    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.

  2. Number of subjects with adverse events [ Time Frame: First 16 weeks of study drug administration and every 4 weeks thereafter (continuous dosing for an anticipated maximum duration of 9 months) ]
  3. Determination of plasma peak concentration (Cmax) of ABT-199 [ Time Frame: Up to Week 24 for ABT-199 ]
    Blood and urine samples for pharmacokinetic analysis of ABT-199 will be collected at designated time points

  4. Determination of trough concentration (Ctrough) of ABT-199 [ Time Frame: Up to Week 24 for ABT-199 ]
    Blood and urine samples for pharmacokinetic analysis of ABT-199 will be collected at designated time points

  5. Determination of area under the concentration versus time curve (AUC) of ABT-199 [ Time Frame: Up to Week 24 for ABT-199 ]
    Blood and urine samples for pharmacokinetic analysis of ABT-199 will be collected at designated time points


Secondary Outcome Measures :
  1. Food Effect - Cmax [ Time Frame: Approximately 3 days ]
    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)

  2. Preliminary efficacy assessment [ Time Frame: 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) ]
    Tumor response or clinical disease progression

  3. Minimal residual disease collection (MRD) [ Time Frame: 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). ]
    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.

  4. Food Effect - Tmax [ Time Frame: Approximately 3 days ]
    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)

  5. Food Effect - AUC [ Time Frame: Approximately 3 days ]
    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)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01328626


Locations
United States, Arizona
University Arizona Cancer Ctr
Tucson, Arizona, United States, 85719-1478
United States, California
UCSD
La Jolla, California, United States, 92037
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065-6007
United States, Texas
Univ TX, MD Anderson
Houston, Texas, United States, 77030
United States, Washington
Swedish Medical Center
Seattle, Washington, United States, 98104
Fred Hutchinson Cancer Researc
Seattle, Washington, United States, 98109
United States, Wisconsin
Univ of Wisconsin Hosp/Clinics
Madison, Wisconsin, United States, 53792-0001
Australia, Victoria
Peter MacCallum Cancer Ctr
Melbourne, Victoria, Australia, 3000
Royal Melbourne Hospital
Parkville, Victoria, Australia, 3050
Sponsors and Collaborators
AbbVie
Genentech, Inc.
Investigators
Study Director: AbbVie Inc. AbbVie

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT01328626     History of Changes
Other Study ID Numbers: M12-175
First Posted: April 5, 2011    Key Record Dates
Last Update Posted: May 10, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by AbbVie:
Safety
Maximum Tolerated Dose
Pharmacokinetics
ABT-199
Preliminary Efficacy
Cancer
Non-Hodgkin Lymphoma
Chronic Lymphocytic Leukemia

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Venetoclax
Antineoplastic Agents