NCT01889186

A Study of the Efficacy of an Active Drug in Subjects With Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia With the 17p Deletion

Brief summary

This is a Phase 2, open label, multicenter, study evaluating the efficacy and safety of an active drug in relapsed or refractory subjects with CLL harboring 17p13 (TP53 locus) deletion. One hundred seven (107) subjects were enrolled in the main cohort, with evaluation of efficacy as the primary objective, and approximately 50 subjects will be enrolled in the safety expansion cohort to evaluate safety and updated tumor lysis syndrome prophylaxis and management measures. Enrollment into the main cohort is closed. Enrollment into the safety expansion cohort is closed.

Interventional study

Status:
Completed
Conditions:
Chronic Lymphocytic Leukemia
17p Deletion
Cancer of the Blood and Bone Marrow
Enrollment:
158 patients
Phase:
  • 1
  • 2
  • 3
  • 4
Protocol ID:
M13-982
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Masking:
None (Open Label)
Purpose:
Treatment

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Eligibility criteria

Participant attributes:
Male and Female

Age:

From 18 Years to 99 Years.

Inclusion Criteria:

- Participant must be greater than or equal to 18 years of age.

- Participant must have diagnosis of chronic lymphocytic leukemia (CLL) that meets
published 2008 Modified IWCLL NCI-WG (International Workshop for Chronic Lymphocytic
Leukemia National Cancer Institute-Working Group) Guidelines.

- Participant has an indication for treatment according to the 2008 Modified IWCLL
NCI WG Guidelines;

- Participant has clinically measurable disease (lymphocytosis > 5 × 10^9/L and/or
palpable and measurable nodes by physical exam and/or organomegaly assessed by
physical exam);

- Participant must be refractory or have relapsed after receiving at least one
prior line of therapy (participants that have progressed after 1 cycle of
treatment or have completed at least 2 cycles of treatment for a given line of
therapy) or previously untreated CLL (previously untreated CLL participants must
have received no prior chemotherapy or immunotherapy. Participants with a history
of emergency, loco-regional radiotherapy (e.g., for relief of compressive signs
or symptoms) are eligible. In addition, participants must meet the CLL diagnostic
criteria above and must have > 5 × 10^9/L B-Lymphocytes in the peripheral
blood.);

- Participants must have 17p deletion, assessed by local laboratory (in bone marrow
or peripheral blood) or assessed by central laboratory (peripheral blood).

- Participant has an Eastern Cooperative Oncology Group (ECOG) performance score of less
than or equal to 2.

- Participant must have adequate bone marrow function at Screening as follows:

- Absolute Neutrophil Count (ANC) greater than or equal to 1000/µL, or

- For subjects with an ANC less than 1000/µL at Screening and bone marrow heavily
infiltrated with underlying disease (unless cytopenia is clearly due to marrow
involvement of CLL), growth factor support may be administered after Screening
and prior to the first dose of ABT-199 to achieve the ANC eligibility criteria
(greater than or equal to 1000/µL);

- Platelets greater than 30,000/mm^3 (without transfusion support within 14 days of
Screening, without evidence of mucosal bleeding, without known history of
bleeding episode within 3 months of Screening, and without history of bleeding
disorder);

- Hemoglobin greater than or equal to 8.0 g/dL.

- Participant must have adequate coagulation, renal, and hepatic function, per
laboratory reference range at Screening as follows:

- Activated partial thromboplastin time (aPTT) and prothrombin time (PT) not to
exceed 1.5 × the upper limit of normal;

- Calculated creatinine clearance greater than 50 mL/min using 24-hour Creatinine
Clearance or modified Cockcroft-Gault equation (using Ideal Body Mass [IBM]
instead of Mass). For participants that have body mass index (BMI) of > 30 kg/m^2
or < 19 kg/m^2, 24-hour measured urine creatinine clearance is required;

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or
equal to 3.0 × the upper normal limit of institution's normal range; Bilirubin
less than or equal to 1.5 × upper limit of normal. Participants with Gilbert's
Syndrome may have a bilirubin greater 1.5 × upper limit of normal, per
correspondence between the investigator and AbbVie medical monitor.

- For participants at high risk of tumor lysis syndrome a pre-approval by the AbbVie
medical monitor is required prior to enrollment.

Exclusion Criteria:

- Participant has undergone an allogeneic stem cell transplant.

- Participant has developed Richter's transformation confirmed by biopsy.

- Participant has prolymphocytic leukemia.

- Participant has active and uncontrolled autoimmune cytopenias (for 2 weeks prior to
Screening), including autoimmune hemolytic anemia and idiopathic thrombocytopenic
purpura despite low dose corticosteroids.

- Participant has previously received ABT-199.

- Participant has received a biologic agent for anti-neoplastic intent within 30 days
prior to the first dose of study drug.

- Participant has received any of the following within 14 days or 5 half-lives as
applicable prior to the first dose of study drug, or has not recovered to less than
Common Toxicity Criteria (CTC) grade 2 clinically significant adverse
effect(s)/toxicity(s) of the previous therapy:

- Any anti-cancer therapy including chemotherapy, or radiotherapy;

- Investigational therapy, including targeted small molecule agents.

- Participant has known allergy to both xanthine oxidase inhibitors and rasburicase.

All the cities where the clinical studies are located

Montreal - H3T 1E2

Quebec