A Study of ABT-263 in Subjects With Relapsed or Refractory Lymphoid Malignancies

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT00406809
First received: November 30, 2006
Last updated: July 31, 2014
Last verified: July 2014
  Purpose

The Phase 1 portion of the study evaluated the pharmacokinetic profile and safety of ABT-263 with the objective of defining the dose limiting toxicity and maximum tolerated dose in subjects with lymphoid malignancies. The Phase 2a portion of the study is evaluating ABT-263 using a step-up dosing regimen and may be increased to the defined recommended Phase 2 dose to obtain additional safety information and a preliminary assessment of efficacy in subject with lymphoid malignancies. The Extension portion of the study is to allow Phase 2a subjects who remain active 1 year after the last subject enrolls or who have been on study approximately 1 year to continue receiving ABT-263 with less frequent study evaluations. Subjects in the Extension Study will continue receiving study drug for up to 5 years after the last subject transitions to the Extension Study, or until disease progression or toxicity that necessitates discontinuation (whichever comes first).


Condition Intervention Phase
Chronic Lymphoid Leukemia
Lymphoid Malignancies
Non-Hodgkin's Lymphoma
Follicular Lymphoma
Mantle Cell Lymphoma
Peripheral T-cell Lymphoma
Drug: ABT-263
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2a Study Evaluating the Safety, Pharmacokinetics and Efficacy of ABT-263 in Subjects With Relapsed or Refractory Lymphoid Malignancies

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Phase 1a: Determine dose limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended Phase 2 dose (RPTD) and schedule - intermittent dosing. [ Time Frame: Repeating sequence of 14 days on therapy and 7 days off. ] [ Designated as safety issue: No ]
    1a: Determination of dose limiting toxicity (DLT) and maximum tolerated dose (MTD) under a 14/21 day dosing schedule

  • Phase 1b: Determine dose limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended Phase 2 dose (RPTD) and schedule - continuous dosing. [ Time Frame: 21 day continuous dosing. ] [ Designated as safety issue: No ]
    Phase 1b: Determination of ABT-263 dose limiting toxicity (DLT) and maximum tolerated dose (MTD) under a 21 day continuous dosing schedule.

  • Phase 2a: Continued assessment of safety profile at the recommended Phase 2 dose (RPTD) and schedule - continuous dosing. [ Time Frame: 21 day continuous dosing. ] [ Designated as safety issue: No ]
    Phase 2a: Continued assessment of the safety profile of ABT-263 at the Recommended Phase 2 Dose (RPTD) and schedule under a 21 day continuous dosing.

  • Phase 2a: Assessment of preliminary efficacy signals including biomarker assessment - continuous dosing. [ Time Frame: 21 day continuous dosing. ] [ Designated as safety issue: No ]
    Phase 2a: Assessment of the preliminary efficacy signals of ABT-263, including biomarker assessment, at the Recommended Phase 2 Dose (RPTD) and schedule under a 21 day continuous dosing.

  • Extension Study: Continued assessment of the safety profile of ABT-263 [ Time Frame: 21 day continuous dosing ] [ Designated as safety issue: No ]
    Continued assessment of the safety profile of ABT-263.

  • Extension Study: Continued assessment of the preliminary efficacy signals of ABT-263. [ Time Frame: day continuous dosing ] [ Designated as safety issue: No ]
    Continued assessment of the preliminary efficacy signals of ABT-263.


Secondary Outcome Measures:
  • Phase 1a or Phase 1b safety assessment [ Time Frame: Repeating sequence of 14 days on therapy and 7 days off OR 21 day continuous dosing. ] [ Designated as safety issue: No ]
    Assessment of the safety of ABT-263

  • Phase 1a, Phase 1b, or Phase 2a pharmacokinetic profile evaluation [ Time Frame: Repeating sequence of 14 days on therapy and 7 days off OR 21 day continuous dosing. ] [ Designated as safety issue: No ]
    Evaluation of pharmacokinetic profile of ABT-263.

  • Phase 1a effect of food on bioavailability [ Time Frame: Repeating sequence of 14 days on therapy and 7 days off. ] [ Designated as safety issue: No ]
    Evaluation of the effect of food on bioavailability


Estimated Enrollment: 110
Study Start Date: November 2006
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 1a and 1b
Relapsed or refractory lymphoid malignancies
Drug: ABT-263

Oral solution

Phase 1 dosing was under two different schedules: 14 days on drug, 7 days off or 21 days continuous dosing.

- 55 subjects with relapsed or refractory lymphoid malignancies. Enrollment is closed in Phase 1 of the study.

Oral solution and tablets

Phase 2a dosing under 21 day continuous dosing.

  • 150 mg lead-in dose for 7-14 days followed by a 325 mg continuous once daily dose.
  • 26 subjects in two arms: Arm A and Arm B. Enrollment is closed in Phase 2a of the study.

Oral tablets

Extension portion of the study is to allow Phase 2a subjects who remain active 1 year after the last subject enrolls or who have been on study approximately 1 year to continue receiving ABT-263 under 21 day continuous dosing.

Experimental: Arm A (Phase 2a)
Relapsed or refractory follicular lymphoma
Drug: ABT-263

Oral solution

Phase 1 dosing was under two different schedules: 14 days on drug, 7 days off or 21 days continuous dosing.

- 55 subjects with relapsed or refractory lymphoid malignancies. Enrollment is closed in Phase 1 of the study.

Oral solution and tablets

Phase 2a dosing under 21 day continuous dosing.

  • 150 mg lead-in dose for 7-14 days followed by a 325 mg continuous once daily dose.
  • 26 subjects in two arms: Arm A and Arm B. Enrollment is closed in Phase 2a of the study.

Oral tablets

Extension portion of the study is to allow Phase 2a subjects who remain active 1 year after the last subject enrolls or who have been on study approximately 1 year to continue receiving ABT-263 under 21 day continuous dosing.

Experimental: Arm B (Phase 2a)
Relapsed or refractory mantle cell, peripheral T-cell, cutaneous T-cell lymphoma including mycosis fungoides and Sezary syndrome, or other indolent B-cell lymphomas such as marginal zone lymphoma
Drug: ABT-263

Oral solution

Phase 1 dosing was under two different schedules: 14 days on drug, 7 days off or 21 days continuous dosing.

- 55 subjects with relapsed or refractory lymphoid malignancies. Enrollment is closed in Phase 1 of the study.

Oral solution and tablets

Phase 2a dosing under 21 day continuous dosing.

  • 150 mg lead-in dose for 7-14 days followed by a 325 mg continuous once daily dose.
  • 26 subjects in two arms: Arm A and Arm B. Enrollment is closed in Phase 2a of the study.

Oral tablets

Extension portion of the study is to allow Phase 2a subjects who remain active 1 year after the last subject enrolls or who have been on study approximately 1 year to continue receiving ABT-263 under 21 day continuous dosing.

Experimental: Extension Study
Relapsed or refractory follicular lymphoma or Relapsed or refractory mantle cell, peripheral T-cell, cutaneous T-cell lymphoma including mycosis fungoides and Sezary syndrome, or other indolent B-cell lymphomas such as marginal zone lymphoma
Drug: ABT-263

Oral solution

Phase 1 dosing was under two different schedules: 14 days on drug, 7 days off or 21 days continuous dosing.

- 55 subjects with relapsed or refractory lymphoid malignancies. Enrollment is closed in Phase 1 of the study.

Oral solution and tablets

Phase 2a dosing under 21 day continuous dosing.

  • 150 mg lead-in dose for 7-14 days followed by a 325 mg continuous once daily dose.
  • 26 subjects in two arms: Arm A and Arm B. Enrollment is closed in Phase 2a of the study.

Oral tablets

Extension portion of the study is to allow Phase 2a subjects who remain active 1 year after the last subject enrolls or who have been on study approximately 1 year to continue receiving ABT-263 under 21 day continuous dosing.


Detailed Description:

Enrollment breakdown: Entered Study: Phase 1a: 39; Phase 1b: 19; Phase 2a: 33; Total: 91 Entered Treatment: Phase 1a: 38; Phase 1b: 17; Phase 2a: 26; Total: 81

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnoses:

    • 1a/1b - lymphoid malignancy;
    • 2a, Arm A - follicular lymphoma;
    • 2a, Arm B - mantle cell, peripheral or cutaneous T-cell lymphomas including mycosis fungoides and Sezary syndrome or other indolent B-cell lymphomas such as marginal zone lymphoma;
  • Received at least 1 prior chemotherapy treatment regimen (P1a/1b) and relapsed or refractory disease (P2a).
  • Eastern Cooperative Oncology Group (ECOG) score of <= 1.
  • Magnetic Resonance Imaging (MRI)/computed tomography (CT) negative for subdural or epidural hematoma w/in 28 days prior to first dose, if clinically indicated.
  • Stable dose of Selective serotonin reuptake inhibitors (SSRI) antidepressants for at least 21 days prior to 1st dose.
  • Adequate bone marrow (BM) independent of any growth factor support (except with heavily infiltrated bone marrow (80% or more)):

    • Absolute Neutrophil Count (ANC) >= 1000/µL;
    • Platelets >= 100,000/mm3 (entry count must be independent of transfusion with in 14 days of Screening);
    • Hemoglobin >= 9.0/dL.
  • Adequate coagulation, renal, and hepatic function:

    • Serum creatinine <= 2.0 mg/dL or calculated creatinine clearance >= 50 mL/min;
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 3.0 x Upper Limit of Normal (ULN);
    • Bilirubin <= 1.5 x ULN;
    • Gilbert's Syndrome may have a bilirubin > 1.5 x ULN;
    • Coagulation: Activated partial thromboplastin time (aPTT), Prothrombin Time (PT), not to exceed 1.2 x ULN
  • Females must be surgically sterile, postmenopausal (at least 1 year), or negative results for a pregnancy test performed at Screening on a serum sample obtained with in 14 days prior to initial dose, and prior to dosing on a urine sample obtained on C1 D-3 (P1a) or Lead-in D1 (P1b, P2a) if > 7 days since serum results.
  • Females not surgically sterile or postmenopausal (at least 1 year) and non-vasectomized males must practice birth control.
  • P2a only: History of autologous stem cell transplant must be > 6 months post transplant with adequate BM independent of growth factor support per lab reference range at Screening as follows:

    • Absolute Neutrophil Count (ANC) >= 1,500/µL;
    • Platelets >= 125,000/mm3 (entry platelet count must be independent of transfusion with in 14 days of Screening);
    • Hemoglobin >= 10.0g/dL;
  • Measurable disease by International Working Group (IWG)/National Cancer Institute- sponsored Working Group (NCI-WG) criteria.
  • At least one of following for Pharmacodynamics (P2a):

    • archived diagnostic Formalin Fixed Paraffin Embedded (FFPE) tumor tissue with no intervening treatment since biopsy,
    • core needle biopsy of malignant lymph node, or
    • bone marrow aspirate or core positive for lymphoma.

Extension Study Inclusion Criteria Phase 2a subjects who enter the Extension Study must continue to meet all Inclusion and Exclusion criteria, with the exception of Inclusion Criterion regarding measurable disease by International Working Group (IWG)/National Cancer Institute- sponsored Working Group (NCI-WG) criteria and Inclusion Criteria regarding laboratory parameters for hematology, coagulation, and chemistry. Subjects entering the Extension Study must also have stable lab values per applicable laboratory reference ranges. In addition, subjects must also meet the following criteria:

  • Subjects must meet the following hematology and coagulation lab criteria:

    • Platelet counts must be >= 25,000/mm3 (untransfused). Platelet counts <= 50,000/mm3 must be stable and monitored at an increased frequency at the discretion of the investigator.
    • Absolute Neutrophil count (ANC) >= 500/µL. ANC >= 500/µL and < 1,000/µL should be monitored at an increased frequency at the discretion of the investigator.
    • Hemoglobin of >= 8.0 g/dL.
    • aPTT, PT is not to exceed 1.2 x ULN.
  • Chemistry values must not exceed Grade 2. Grade 2 chemistry labs should be monitored at an increased frequency at the discretion of the investigator. Subjects must meet the following chemistry criteria:

    • Serum creatinine <= 3.0 x the upper normal limit (ULN) of institution's normal range. * AST and ALT <= 5.0 x the upper normal limit (ULN) of institution's normal range.
    • Bilirubin <= 3.0 x ULN. Subjects with Gilbert's Syndrome may be allowed to have a Bilirubin > 3.0 x ULN based on a joint decision between the investigator and Abbott medical monitor.

Exclusion Criteria:

  • History of, or is, clinically suspicious for cancer-related Central Nervous System (CNS) disease, lymphoid or non-lymphoid.
  • Undergone an allogeneic or autologous stem cell transplant.
  • Underlying, predisposing condition of bleeding or currently exhibits signs of clinically significant bleeding.
  • Recent history of non-chemotherapy induced thrombocytopenic associated bleeding with in 1 year prior to first dose.
  • Active peptic ulcer disease or other hemorrhagic esophagitis/gastritis.
  • Active immune thrombocytopenic purpura or history of being refractory to platelet transfusions with in 1 year prior to first dose.
  • Significant history of cardiovascular disease, renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, or hepatic disease.
  • Females pregnant or breast-feeding.
  • Positive for human immunodeficiency virus (HIV)
  • History of other active malignancies with in the past 3 years (P1a/1b) or past 5 years (P2a), except adequately treated in situ carcinoma of the cervix uteri; basal or squamous cell carcinoma; in situ carcinoma of the bladder; previous malignancy confined and surgically resected with curative intent.
  • Evidence of other clinically significant uncontrolled condition(s), including, but not limited to active systemic fungal infection; diagnosis of fever and neutropenia with in 1 week prior to study drug.
  • Received steroid therapy with in 7 days prior to 1st dose of study drug for anti-neoplastic intent.
  • Received any anti-cancer therapy, including chemotherapy, immunotherapy, radiotherapy, hormonal or any investigational therapy, with in 14 days prior to first dose of study drug, or has not recovered to <Gr2 clinically significant AE(s) /toxicity(s) of the previous therapy.
  • Received a biologic with in 30 days prior to first dose.
  • Currently receiving or requires anticoagulation therapy or any drugs or herbal supplements that affect platelet function, with the exception of low-dose anticoagulation medications that are used to maintain the patency of a central venous catheter.
  • Received aspirin with in 7 days prior to first dose and during ABT-263 administration.
  • Consumed grapefruit or grapefruit products with in 3 days prior to first dose.
  • P1a/1b only: Diagnosed with Posttransplant lymphoproliferative disorder (PTLD); Burkitt's, Burkitt-like, or HIV-associate lymphoma; lymphoblastic lymphoma/leukemia; or multiple myeloma.
  • Subject has received CYP3A inhibitors (e.g., ketoconazole, clarithromycin) within 7 days prior to the administration of the first dose of ABT-263 (P2a).
  • Subject had a prior significant toxicity from another Bcl-2 family protein inhibitor (P2a).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00406809

Locations
United States, California
Site Reference ID/Investigator# 4997
Los Angeles, California, United States, 90033
Site Reference ID/Investigator# 9104
Los Angeles, California, United States, 90095
United States, Maryland
Site Reference ID/Investigator# 2613
Bethesda, Maryland, United States, 20892
United States, Massachusetts
Site Reference ID/Investigator# 4745
Boston, Massachusetts, United States, 02215
Site Reference ID/Investigator# 40243
Boston, Massachusetts, United States, 02215
United States, New York
Site Reference ID/Investigator# 2628
Buffalo, New York, United States, 14263
Site Reference ID/Investigator# 2614
New York, New York, United States, 10032
Site Reference ID/Investigator# 2627
New York, New York, United States, 10021
Site Reference ID/Investigator# 5383
New York, New York, United States, 10065
Site Reference ID/Investigator# 23543
New York, New York, United States, 10016
Site Reference ID/Investigator# 12306
Rochester, New York, United States, 14642
Canada
Site Reference ID/Investigator# 8941
Edmonton, Canada, T6G 1Z2
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Sari Enschede, MD AbbVie
  More Information

No publications provided by AbbVie

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT00406809     History of Changes
Obsolete Identifiers: NCT00408811
Other Study ID Numbers: M06-814
Study First Received: November 30, 2006
Last Updated: July 31, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by AbbVie:
follicular lymphoma
mantle cell lymphoma
peripheral T-cell lymphoma
cutaneous T-cell lymphoma
mycosis fungoides
Sezary syndrome
marginal zone lymphoma
Navitoclax
ABT-263
chronic lymphoid leukemia
lymphoid malignancies
indolent T-cell lymphoma
Non-Hodgkin's lymphoma

Additional relevant MeSH terms:
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Neoplasms
Lymphoma, Mantle-Cell
Lymphoma, T-Cell
Lymphoma
Leukemia
Lymphoma, T-Cell, Peripheral
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Navitoclax
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 01, 2014