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A Phase 1/2a Study Evaluating the Safety, Pharmacokinetics and Efficacy of ABT-263 in Subjects With Relapsed or Refractory Lymphoid Malignancies


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Chronic Lymphoid Leukemia, Lymphoid Malignancies, Non-Hodgkin's Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, Peripheral T-cell Lymphoma

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Trial Information

A Phase 1/2a Study Evaluating the Safety, Pharmacokinetics and Efficacy of ABT-263 in Subjects With Relapsed or Refractory Lymphoid Malignancies


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


Inclusion Criteria:



- >= 18 years of age.

- 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 Formulin 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 /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).

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Description:

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

Outcome Time Frame:

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

Safety Issue:

No

Principal Investigator

Sari Enschede, MD

Investigator Role:

Study Director

Investigator Affiliation:

AbbVie

Authority:

United States: Food and Drug Administration

Study ID:

M06-814

NCT ID:

NCT00406809

Start Date:

November 2006

Completion Date:

October 2014

Related Keywords:

  • Chronic Lymphoid Leukemia
  • Lymphoid Malignancies
  • Non-Hodgkin's Lymphoma
  • Follicular Lymphoma
  • Mantle Cell Lymphoma
  • Peripheral T-cell Lymphoma
  • 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
  • Neoplasms
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Non-Hodgkin
  • Lymphoma, T-Cell
  • Lymphoma, T-Cell, Peripheral
  • Lymphoma, Mantle-Cell

Name

Location

Site Reference ID/Investigator# 4997Los Angeles, California  90033
Site Reference ID/Investigator# 9104Los Angeles, California  90095
Site Reference ID/Investigator# 2613Bethesda, Maryland  20892
Site Reference ID/Investigator# 4745Boston, Massachusetts  02115
Site Reference ID/Investigator# 40243Boston, Massachusetts  02115
Site Reference ID/Investigator# 2628Buffalo, New York  14263
Site Reference ID/Investigator# 2614New York, New York  10032
Site Reference ID/Investigator# 2627New York, New York  10021
Site Reference ID/Investigator# 5383New York, New York  10021
Site Reference ID/Investigator# 23543New York, New York  10016
Site Reference ID/Investigator# 12306Rochester, New York  14642