Study Evaluating ABT-199 in Subjects With Relapsed or Refractory Multiple Myeloma



Status:Suspended
Conditions:Blood Cancer, Hematology
Therapuetic Areas:Hematology, Oncology
Healthy:No
Age Range:18 - 99
Updated:3/23/2019
Start Date:October 10, 2012
End Date:December 31, 2021

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A Phase I/II Study Evaluating the Safety and Pharmacokinetics of ABT-199 in Subjects With Relapsed or Refractory Multiple Myeloma

The phase 1 primary objectives of this study are to assess the safety profile, characterize
pharmacokinetics (PK) and determine the dosing schedule, maximum tolerated dose (MTD), and
recommended phase 2 dose (RPTD) of ABT-199 (venetoclax) when administered in subjects with
relapsed or refractory multiple myeloma. This study will also assess the safety profile and
PK of venetoclax in combination with dexamethasone in subjects with t(11;14)-positive
multiple myeloma.

The phase 2 primary objective is to further evaluate the objective response rate (ORR) and
very good partial response or better rate (VGPR+) in subjects with t(11;14)-positive multiple
myeloma.


Inclusion Criteria:

- ECOG (Eastern Cooperative Oncology Group) performance score of 1 or 0. Subjects in the
Phase 2 portion: ECOG performance score of 2, 1, or 0.

- Diagnosis of multiple myeloma previously treated with at least one prior line of
therapy. Induction therapy followed by stem cell transplant and maintenance therapy
will be considered a single line of therapy. For Safety Expansion, subjects must have
been previously treated with a proteasome inhibitor (e.g., bortezomib) and an
immunomodulatory agent (e.g., thalidomide, lenalidomide). For Venetoclax-Dexamethasone
Combination, subjects must have been been previously treated with a proteasome
inhibitor (e.g., bortezomib) and an immunomodulatory agent (e.g., thalidomide,
lenalidomide) AND have t(11;14)-positive multiple myeloma per the central lab testing.
For Phase 2, subjects must have MM positive for the t(11;14) translocation, as
determined by an analytically validated fluorescence in situ hybridization (FISH)
assay per the central laboratory testing (enrollment with local t(11;14)-positive FISH
results only will be considered at the discretion of the TA MD) Subjects must have
evidence of disease progression on or within 60 days of last dose of most recent
previous treatment based on IMWG criteria AND Subject must have previously received at
least 2 lines of therapy, including an immunomodulatory drug (lenalidomide or
pomalidomide), a proteasome inhibitor (bortezomib, carfilzomib or ixazomib),
daratumumab, and glucocorticoids.

- For US subjects: Daratumumab combination regimen must be one of the prior lines
of therapy (for this study, daratumumab plus corticosteroids will not be
considered a combination regimen)

- For Non-US Subjects: Either daratumumab monotherapy or combination therapy is
acceptable. Daratumumab monotherapy will be limited to approximately 20 percent
of the total number of Phase 2 subjects.

- Measurable disease at Screening: Serum monoclonal protein of at least 1.0 g/dL (10g/L)
by protein electrophoresis or at least 200 mg of monoclonal protein in the urine on
24-hr electrophoresis or serum immunoglobulin free light chain of at least 10 mg/dL
and abnormal serum immunoglobulin kappa to lambda free light chain ratio.

- Subjects with a history of autologous or allogenic stem cell transplantation must have
adequate peripheral blood counts independent of any growth factor support, and have
recovered from any transplant related toxicity(s) and be at least 100 days
post-autologous transplant prior to first dose of study drug or at least 6 months
post-allogenic transplant prior to first dose of study drug and not have active
graft-versus-host disease (GVHD), i.e., requiring treatment.

- Meet the following laboratory parameters, per the reference range, at least once
during the screening period: ANC of at least 1000/μL (Subjects may use growth factor
support to achieve ANC eligibility criteria), AST and ALT not higher than 3 x ULN,
Calculated creatinine clearance of at least 30 mL/min using a modified Cockcroft-Gault
calculation, platelet count of at least 30,000 mm³ (independent of transfusion for 2
weeks), hemoglobin of at least 8.0 g/dL (subjects may receive blood transfusion to
achieve hemoglobin eligibility criteria), and total bilirubin not higher than 1.5 x
ULN (subjects with Gilbert's Syndrome may have bilirubin higher 1.5 x ULN).

Exclusion Criteria:

- Exhibits evidence of other clinically significant uncontrolled condition(s),
including, but not limited to: uncontrolled systemic infection (viral, bacterial, or
fungal), diagnosis of fever and neutropenia within 1 week prior to first dose of study
drug.

- Cardiovascular disability status of New York Heart Association Class greater than or
equal to 3.

- Significant history of renal, neurologic, psychiatric, endocrinologic, metabolic,
immunologic, cardiovascular or hepatic disease, within the last 6 months that, in the
opinion of the investigator, would adversely affect his/her participation in the
study.

- History of other active malignancies other than multiple myeloma within the past 3
years prior to study entry, with the following exceptions: adequately treated in situ
carcinoma of the cervix uteri, basal cell carcinoma of the skin or localized squamous
cell carcinoma of the skin, localized prostate cancer Gleason grade 6 or lower AND
with stable prostate specific antigen (PSA) levels off treatment, previous malignancy
confined and surgically resected (or treated with other modalities) with curative
intent.

- Known HIV infection.

- Active hepatitis B or C infection
We found this trial at
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660 South Euclid Avenue
Saint Louis, Missouri 63110
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Ann Arbor, Michigan 48109
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Atlanta, Georgia 30322
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Durham, North Carolina 27710
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Greensboro, North Carolina 27401
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Hackensack, New Jersey 07601
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Harvey, Illinois 60426
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New Haven, Connecticut 06510
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Rochester, Minnesota 55905
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