A Phase 1b Study Evaluating the Safety and Tolerability of ABT-199 in Combination With Rituximab in Subjects With Relapsed Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

June 5, 2023 updated by: AbbVie
This is a Phase 1b, open-label, multicenter study evaluating the safety and tolerability of ABT-199 in combination with rituximab in up to 50 subjects with Relapsed Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma. The primary objectives of this study are to assess the safety profile, to determine the maximum tolerated dose and establish the Recommended Phase Two Dose of ABT-199 when administered in combination with rituximab. The dose escalation portion of the study will include approximately 30 subjects. Once the recommended phase two dose and schedule have been determined, up to 20 additional subjects will be enrolled in an expanded safety portion of the study. Subjects who meet criteria for CR, CRi, or MRD-negative PR during the study may discontinue ABT 199. If disease progression occurs, as defined by iwCLL NCI/WG criteria for tumor response, or MRD progression, subjects may re-initiate ABT-199.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

49

Phase

  • Phase 1

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • Peter MacCallum Cancer Ctr /ID# 70394
      • Parkville, Victoria, Australia, 3050
        • The Royal Melbourne Hospital /ID# 70393
  • United States
    • California
      • La Jolla, California, United States, 92093
        • Moores Cancer Center at UC San Diego /ID# 70398
    • Illinois
      • Chicago, Illinois, United States, 60611-2927
        • Northwestern University Feinberg School of Medicine /ID# 71593
    • New York
      • New Hyde Park, New York, United States, 11040
        • North Shore University Hospital /ID# 71813
    • North Carolina
      • Durham, North Carolina, United States, 27710-3000
        • Duke Cancer Center /ID# 71393

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 97 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Subject must be greater then or equal to 18 years of age.
  • Subject must have relapsed Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma.
  • Subject has an Eastern Cooperative Oncology Group performance score of 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:

  • Chronic lymphocytic leukemia or Small Lymphocytic Lymphoma subject has undergone an allogeneic or autologous stem cell transplant.
  • Subject has uncontrolled autoimmune hemolytic anemia or thrombocytopenia.
  • Subject has tested positive for human immunodeficiency virus.
  • Seropositivity for hepatitis B surface antigen or hepatitis C virus antibody or ribonucleic acid.
  • History of severe allergic or anaphylactic reactions to rituximab.
  • Subject has received a live viral vaccine within 6 months prior to the first dose of study drug.
  • Subject has received a monoclonal antibody for anti-neoplastic intent within 8 weeks prior to the first dose of study drug.

  • Subject has received any of the following within 14 days prior to the first dose of study drug, or has not recovered to less than grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy:

    • Any anti-cancer therapy including chemotherapy, immunotherapy, or radiotherapy;
    • Investigational therapy, including targeted small molecule agents.
  • Subject has a cardiovascular disability status of New York Heart Association Class greater then or equal to 2. Class 2 is defined as cardiac disease in which subjects 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 a history of other active malignancies other than CLL/SLL within the past 2 years prior to study entry, with the exception of:

    • Adequately treated in situ carcinoma of the cervix uteri;
    • Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
    • Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
  • Subject has malabsorption syndrome or other condition that precludes enteral route of administration.

  • Subject exhibits evidence of other clinically significant ongoing or recent condition(s) including, but not limited to:

    • Ongoing systemic infection (viral, bacterial, or fungal);
    • Diagnosis of fever and neutropenia within 1 week prior to study drug administration

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1
Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL)
Drug: ABT-199
ABT-199 is taken continuously once daily. This is a dose escalation study, therefore the dose of ABT-199 will change throughout the study.
Other Names:
  • venetoclax
Drug: Rituximab
Rituximab will be given by intravenous infusion on day 1 of Months 1, 2, 3, 4, 5, and 6. May be reinitiated for an additional 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assess the safety profile, to determine the maximum tolerated dose and Recommended Phase Two Dose of ABT-199 when administered in combination with rituximab (R) in subjects with relapsed chronic lymphocytic leukemia and small lymphocytic lymphoma.
Time Frame: Continuous dosing at designated dose level up to Month 6. At end of combination treatment, ABT-199 monotherapy may continue up to 8 years following the date of the last subject enrolled. If disease progression occurs, subjects may re-initiate ABT-199.
Protocol-defined events, which are attributed as having a reasonable possibility of being related to the administration of ABT-199 and/or rituximab, or can not be attributed by the investigator to a clearly identifiable cause such as tumor progression, concurrent illness, underlying disease or concomitant medication, will be considered a dose limiting toxicity.
Continuous dosing at designated dose level up to Month 6. At end of combination treatment, ABT-199 monotherapy may continue up to 8 years following the date of the last subject enrolled. If disease progression occurs, subjects may re-initiate ABT-199.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determination of peak concentration (Cmax) of ABT-199 and/or Rituximab.
Time Frame: PK samples collected up to Month 6 for ABT-199 and Rituximab
Blood samples for analysis of ABT-199 and rituximab will be collected at designated time points.
PK samples collected up to Month 6 for ABT-199 and Rituximab
Assess the exploratory efficacy of the combination ABT-199 and rituximab.
Time Frame: Tumor Assessments will be performed at: Screening, Day 1 on Months 1, 3, 7, and then every 3 months thereafter up to 8 years following the date of the last subject first dose.
Tumor response or clinical disease progression (Objective Response Rate)
Tumor Assessments will be performed at: Screening, Day 1 on Months 1, 3, 7, and then every 3 months thereafter up to 8 years following the date of the last subject first dose.
Determination of trough concentration (Ctrough) of ABT-199 and/or Rituximab
Time Frame: PK samples collected up to Month 6 for ABT-199 and Rituximab
Blood samples for analysis of ABT-199 and rituximab will be collected at designated time points.
PK samples collected up to Month 6 for ABT-199 and Rituximab
Determination of area under the concentration versus time curve (AUC) of ABT-199 and/or Rituximab
Time Frame: PK samples collected up to Month 6 for ABT-199 and Rituximab
Blood samples for analysis of ABT-199 and rituximab will be collected at designated time points.
PK samples collected up to Month 6 for ABT-199 and Rituximab
Assess the exploratory efficacy of the combination ABT-199 and rituximab
Time Frame: Tumor Assessments will be performed at: Screening, Day 1 on Months 1, 3, 7, and then every 3 months thereafter up to 8 years following the date of the last subject first dose.
Tumor response or clinical disease progression for (Overall Survival)
Tumor Assessments will be performed at: Screening, Day 1 on Months 1, 3, 7, and then every 3 months thereafter up to 8 years following the date of the last subject first dose.
Assess the exploratory efficacy of the combination ABT-199 and rituximab
Time Frame: Tumor Assessments will be performed at: Screening, Day 1 on Months 1, 3, 7, and then every 3 months thereafter up to 8 years following the date of the last subject first dose.
Tumor response or clinical disease progression for (Progression Free Survival)
Tumor Assessments will be performed at: Screening, Day 1 on Months 1, 3, 7, and then every 3 months thereafter up to 8 years following the date of the last subject first dose.
Assess the exploratory efficacy of the combination ABT-199 and rituximab
Time Frame: Tumor Assessments will be performed at: Screening, Day 1 on Months 1, 3, 7, and then every 3 months thereafter up to 8 years following the date of the last subject first dose.
Tumor response or clinical disease progression for (Time to Tumor Progression)
Tumor Assessments will be performed at: Screening, Day 1 on Months 1, 3, 7, and then every 3 months thereafter up to 8 years following the date of the last subject first dose.
Assess the exploratory efficacy of the combination ABT-199 and rituximab
Time Frame: Tumor Assessments will be performed at: Screening, Day 1 on Months 1, 3, 7, and then every 3 months thereafter up to 8 years following the date of the last subject first dose.
Tumor response or clinical disease progression for (Duration Of Response)
Tumor Assessments will be performed at: Screening, Day 1 on Months 1, 3, 7, and then every 3 months thereafter up to 8 years following the date of the last subject first dose.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assess the exploratory pharmacodynamics and pharmacogenetics of the combination of ABT-199 and rituximab.
Time Frame: MRD Assessments will be performed at following timepoints: At least 2 months after CR/CRi criteria for tumor response first met, every 12 weeks thereafter until MRD negativity is achieved, and as needed.
Minimal residual disease (MRD) will be assessed in the peripheral blood and bone marrow (BM) either by flow cytometry or real-time PCR.
MRD Assessments will be performed at following timepoints: At least 2 months after CR/CRi criteria for tumor response first met, every 12 weeks thereafter until MRD negativity is achieved, and as needed.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AbbVie

Collaborators

Genentech, Inc.

Investigators

  • Study Director: ABBVIE INC., AbbVie

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 25, 2012

Primary Completion (Actual)

June 23, 2022

Study Completion (Actual)

June 23, 2022

Study Registration Dates

First Submitted

June 26, 2012

First Submitted That Met QC Criteria

September 7, 2012

First Posted (Estimated)

September 11, 2012

Study Record Updates

Last Update Posted (Actual)

June 6, 2023

Last Update Submitted That Met QC Criteria

June 5, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M13-365

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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