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Chronic Lymphoid LeukemiaPhase 1/2NCT00406809

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

A Phase 1/2 study testing ABT-263 in people with Chronic Lymphoid Leukemia and Lymphoid Malignancies, run by AbbVie (prior sponsor, Abbott) at 12 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 99 years
What is being tested?
ABT-263
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
81 participants
Where
12 sitesin 2 countries
Study dates
Nov 2006to Oct 2016
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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).

Trial locations and contacts

12 sites in 2 countries.

12 sites in 2 countries

United States11 sites

  • Site Reference ID/Investigator# 2613

    Bethesda, Maryland, 20892

  • Site Reference ID/Investigator# 40243

    Boston, Massachusetts, 02215

  • Site Reference ID/Investigator# 4745

    Boston, Massachusetts, 02215

  • Site Reference ID/Investigator# 2628

    Buffalo, New York, 14263

  • Site Reference ID/Investigator# 4997

    Los Angeles, California, 90033

  • Site Reference ID/Investigator# 9104

    Los Angeles, California, 90095

  • Site Reference ID/Investigator# 23543

    New York, New York, 10016

  • Site Reference ID/Investigator# 2627

    New York, New York, 10021

  • Site Reference ID/Investigator# 2614

    New York, New York, 10032

  • Site Reference ID/Investigator# 5383

    New York, New York, 10065

  • Site Reference ID/Investigator# 12306

    Rochester, New York, 14642

Other trials in United States

Canada1 site

  • Site Reference ID/Investigator# 8941

    Edmonton, T6G 1Z2

Other trials in Canada

About this study

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

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).

Read the 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

Being tested
ABT-263
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
Medical subject headings
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

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ABT-263Drug

    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.
Study groups in NCT00406809
Study groupRoleWhat they receive
Phase 1a and 1bExperimentalRelapsed or refractory lymphoid malignancies
Receives: Drug: ABT-263
Arm A (Phase 2a)ExperimentalRelapsed or refractory follicular lymphoma
Receives: Drug: ABT-263
Arm B (Phase 2a)ExperimentalRelapsed 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
Receives: Drug: ABT-263
Extension StudyExperimentalRelapsed 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
Receives: Drug: ABT-263

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

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

  2. 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.

    Measured: 21 day continuous dosing.

  3. 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.

    Measured: 21 day continuous dosing.

  4. 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.

    Measured: 21 day continuous dosing.

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

    Continued assessment of the safety profile of ABT-263.

    Measured: 21 day continuous dosing

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

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

    Measured: day continuous dosing

Secondary outcomes (3)

  1. Phase 1a or Phase 1b safety assessment

    Assessment of the safety of ABT-263

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

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

    Evaluation of pharmacokinetic profile of ABT-263.

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

  3. Phase 1a effect of food on bioavailability

    Evaluation of the effect of food on bioavailability

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Dec 2006 (estimated)
  2. Study startNov 2006
  3. Primary completionOct 2016
  4. Study completionOct 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
81 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00406809
Sponsor's protocol ID
M06-814
Status last verified
Jul 2021
First submitted
30 Nov 2006
Last updated
2 Aug 2021
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 21094089

  • 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.

    PubMed 33236943

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ABT-263 in people with Chronic Lymphoid Leukemia and Lymphoid Malignancies, run by AbbVie (prior sponsor, Abbott) at 12 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 38 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00406809, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2021.

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