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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

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ClinicalTrials.gov Identifier: NCT01682616
Recruitment Status : Completed
First Posted : September 11, 2012
Last Update Posted : June 6, 2023
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
AbbVie

Study Description
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Brief Summary:
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.

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

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 49 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 25, 2012
Actual Primary Completion Date : June 23, 2022
Actual Study Completion Date : June 23, 2022

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Arms and Interventions
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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 Name: 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.


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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)

  3. 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.

  4. 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.

  5. 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)

  6. 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)

  7. 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)

  8. 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)


Other Outcome Measures:
  1. 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.


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

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
Contacts and Locations
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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): NCT01682616


Locations
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United States, California
Moores Cancer Center at UC San Diego /ID# 70398
La Jolla, California, United States, 92093
United States, Illinois
Northwestern University Feinberg School of Medicine /ID# 71593
Chicago, Illinois, United States, 60611-2927
United States, New York
North Shore University Hospital /ID# 71813
New Hyde Park, New York, United States, 11040
United States, North Carolina
Duke Cancer Center /ID# 71393
Durham, North Carolina, United States, 27710-3000
Australia, Victoria
Peter MacCallum Cancer Ctr /ID# 70394
Melbourne, Victoria, Australia, 3000
The Royal Melbourne Hospital /ID# 70393
Parkville, Victoria, Australia, 3050
Sponsors and Collaborators
AbbVie
Genentech, Inc.
Investigators
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Study Director: ABBVIE INC. AbbVie
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT01682616    
Other Study ID Numbers: M13-365
First Posted: September 11, 2012    Key Record Dates
Last Update Posted: June 6, 2023
Last Verified: June 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia
Rituximab
Tolerability
Pharmacokinetics
 ABT-199
Cancer
Preliminary
Efficacy
Maximum Tolerated Dose
Venetoclax
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hematologic Diseases
 Leukemia, B-Cell
Chronic Disease
Disease Attributes
Pathologic Processes
Rituximab
Venetoclax
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents