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

NCT00406809 | Completed Phase 1

• 1 other identifier: M06-814
• Study Type: interventional
• Target: 81
• Locations: 2 countries
• Sites: 12

Brief Summary

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 7 years after the last subject transitions to the Extension Study, or until disease progression or toxicity that necessitates discontinuation (whichever comes first).

Conditions

Chronic Lymphoid Leukemia; Lymphoid Malignancies; Non-Hodgkin's Lymphoma; Follicular Lymphoma; Mantle Cell Lymphoma; Peripheral T-cell Lymphoma

Keywords

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

Outcome Measures

Primary Outcomes (6)

• Phase 1a: Determine dose limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended Phase 2 dose (RPTD) and schedule - intermittent dosing.

  1a: Determination of dose limiting toxicity (DLT) and maximum tolerated dose (MTD) under a 14/21 day dosing schedule

  Repeating sequence of 14 days on therapy and 7 days off.

• Phase 1b: Determine dose limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended Phase 2 dose (RPTD) and schedule - continuous dosing.

  Phase 1b: Determination of ABT-263 dose limiting toxicity (DLT) and maximum tolerated dose (MTD) under a 21 day continuous dosing schedule.

  21 day continuous dosing.

• Phase 2a: Continued assessment of safety profile at the recommended Phase 2 dose (RPTD) and schedule - continuous dosing.

  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.

  21 day continuous dosing.

• Phase 2a: Assessment of preliminary efficacy signals including biomarker assessment - continuous dosing.

  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.

  21 day continuous dosing.

• Extension Study: Continued assessment of the safety profile of ABT-263

  Continued assessment of the safety profile of ABT-263.

  21 day continuous dosing

• Extension Study: Continued assessment of the preliminary efficacy signals of ABT-263.

  Continued assessment of the preliminary efficacy signals of ABT-263.

  day continuous dosing

Secondary Outcomes (3)

• Phase 1a or Phase 1b safety assessment

  Repeating sequence of 14 days on therapy and 7 days off OR 21 day continuous dosing.

• Phase 1a, Phase 1b, or Phase 2a pharmacokinetic profile evaluation

  Repeating sequence of 14 days on therapy and 7 days off OR 21 day continuous dosing.

• Phase 1a effect of food on bioavailability

  Repeating sequence of 14 days on therapy and 7 days off.

Study Arms (4)

Phase 1a and 1b

EXPERIMENTAL

Relapsed or refractory lymphoid malignancies

Drug: ABT-263

Arm A (Phase 2a)

EXPERIMENTAL

Relapsed or refractory follicular lymphoma

Drug: ABT-263

Arm B (Phase 2a)

EXPERIMENTAL

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

Extension Study

EXPERIMENTAL

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

Interventions

ABT-263 DRUG

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

Arm A (Phase 2a); Arm B (Phase 2a); Extension Study; Phase 1a and 1b

Eligibility Criteria

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

You may qualify if:

• Diagnoses:
• a/1b - lymphoid malignancy;
• a, Arm A - follicular lymphoma;
• a, 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);

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead

Study Sites (12)

Site Reference ID/Investigator# 4997

Los Angeles, California, 90033, United States

Location

Site Reference ID/Investigator# 9104

Los Angeles, California, 90095, United States

Location

Site Reference ID/Investigator# 2613

Bethesda, Maryland, 20892, United States

Location

Site Reference ID/Investigator# 40243

Boston, Massachusetts, 02215, United States

Location

Site Reference ID/Investigator# 4745

Boston, Massachusetts, 02215, United States

Location

Site Reference ID/Investigator# 2628

Buffalo, New York, 14263, United States

Location

Site Reference ID/Investigator# 23543

New York, New York, 10016, United States

Location

Site Reference ID/Investigator# 2627

New York, New York, 10021, United States

Location

Site Reference ID/Investigator# 2614

New York, New York, 10032, United States

Location

Site Reference ID/Investigator# 5383

New York, New York, 10065, United States

Location

Site Reference ID/Investigator# 12306

Rochester, New York, 14642, United States

Location

Site Reference ID/Investigator# 8941

Edmonton, T6G 1Z2, Canada

Location

Related Publications (2)

• Wilson WH, O'Connor OA, Czuczman MS, LaCasce AS, Gerecitano JF, Leonard JP, Tulpule A, Dunleavy K, Xiong H, Chiu YL, Cui Y, Busman T, Elmore SW, Rosenberg SH, Krivoshik AP, Enschede SH, Humerickhouse RA. Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: a phase 1 dose-escalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity. Lancet Oncol. 2010 Dec;11(12):1149-59. doi: 10.1016/S1470-2045(10)70261-8. Epub 2010 Nov 18.

  PMID: 21094089 BACKGROUND

• de Vos S, Leonard JP, Friedberg JW, Zain J, Dunleavy K, Humerickhouse R, Hayslip J, Pesko J, Wilson WH. Safety and efficacy of navitoclax, a BCL-2 and BCL-XL inhibitor, in patients with relapsed or refractory lymphoid malignancies: results from a phase 2a study. Leuk Lymphoma. 2021 Apr;62(4):810-818. doi: 10.1080/10428194.2020.1845332. Epub 2020 Nov 25.

  PMID: 33236943 DERIVED

MeSH Terms

Conditions

Leukemia, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, T-Cell, Peripheral; Sezary Syndrome; Lymphoma, T-Cell, Cutaneous; Lymphoma, B-Cell, Marginal Zone; Mycosis Fungoides

Interventions

navitoclax

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma; Lymphoma, T-Cell; Lymphoma, B-Cell

Study Officials

• Mack Mabry, MD

  AbbVie

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: November 30, 2006
• First Posted: December 4, 2006
• Study Start: November 1, 2006
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: August 2, 2021

Record last verified: 2021-07

Locations

CA (1); US (11)