A Study of Combination Therapy With Venetoclax, Daratumumab and Dexamethasone (With and Without Bortezomib) in Subjects With Relapsed or Refractory Multiple Myeloma



Status:Suspended
Conditions:Blood Cancer, Hematology, Hematology
Therapuetic Areas:Hematology, Oncology
Healthy:No
Age Range:18 - Any
Updated:3/23/2019
Start Date:March 12, 2018
End Date:March 22, 2023

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A Phase 1/2, Multicenter, Dose-Escalation and Expansion Study of Combination Therapy With Venetoclax, Daratumumab and Dexamethasone (With and Without Bortezomib) in Subjects With Relapsed or Refractory Multiple Myeloma

This is a study of venetoclax, daratumumab, and dexamethasone with and without bortezomib
combination therapy to evaluate safety, tolerability, and efficacy of these combinations in
participants with relapsed or refractory multiple myeloma. The study will consist of 2
distinct parts: Part 1 includes participants with t(11;14) positive relapsed/refractory (R/R)
multiple myeloma who will receive venetoclax in combination with daratumumab and
dexamethasone (VenDd); Part 2 includes participants with R/R multiple myeloma who will
receive venetoclax in combination with daratumumab, bortezomib, and dexamethasone (VenDVd).

Each Part will be initiated with a dose-escalation phase in which increasing doses of
venetoclax will be given with fixed doses of daratumumab and dexamethasone (Part 1a) or with
fixed doses of daratumumab, bortezomib, and dexamethasone (Part 2a). Each dose escalation
phase will be followed by a single-arm, open-label expansion phase.


Inclusion Criteria:

- Eastern Cooperative Oncology Group (ECOG) performance status <= 2.

- Participant has relapsed or refractory multiple myeloma with documented evidence of
progression that occurred during or after the participant's last treatment regimen
based on investigator's determination of International Myeloma Working Group (IMWG)
criteria.

- Measurable disease confirmed by central lab at Screening, defined by at least 1 of the
following:

1. Serum M-protein >= 1.0 g/dL (>= 10 g/L), OR

2. Urine M-protein >= 200 mg/24 hours, OR

3. Serum free light chain (FLC) >= 10 mg/dL, provided serum FLC ratio is abnormal in
participants who do not have measurable disease by Serum Protein Electrophoresis
(SPEP) or Urine Protein Electrophoresis (UPEP) criteria.

- Participant has received previous multiple myeloma treatment as defined in the
protocol for Part 1 and Part 2 of this study.

- Bone marrow aspirate samples have been collected.

- To qualify for Part 1, the participant must be t(11;14) positive as determined by an
analytically validated Fluorescent In Situ Hybridization (FISH) assay per central
laboratory testing.

- Participants must have adequate hematologic, renal and hepatic function.

Exclusion Criteria:

- Previous treatment with venetoclax or other B-Cell Lymphoma 2 (BCL-2) inhibitor OR
previous treatment with daratumumab or other anti-CD38 therapy.

- For participants in Part 2:

1. Participant is refractory to any proteasome inhibitor, defined as progression on
or within 60 days of the last dose of a proteasome inhibitor-containing regimen.

2. Participant has had prior treatment with proteasome inhibitor within 60 days
prior to first dose of study drug.

- Treatment with anti-myeloma chemotherapy, radiotherapy, biological, immunotherapy or
an investigational therapy, including targeted small molecule agents within 2 weeks or
5 half-lives (whichever is longer and/or applicable) before first dose.

- Treatment with anti-myeloma monoclonal antibodies within 6 weeks prior first dose.

- Recent corticosteroid therapy at a cumulative dose equivalent to >= 140 mg of
prednisone or a single dose equivalent to >= 40 mg of dexamethasone within 2 weeks
prior the first dose of study drug.

- Known meningeal involvement of multiple myeloma.

- Significant history of medical conditions as listed in the protocol.
We found this trial at
13
sites
Charlotte, North Carolina 28203
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Charlotte, NC
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Atlanta, Georgia 30322
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Atlanta, GA
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Aurora, CO
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Boston, Massachusetts 02215
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Boston, MA
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Boston, Massachusetts 02215
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Boston, MA
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Buffalo, New York 14263
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Buffalo, NY
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Chicago, Illinois 60637
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Chicago, IL
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Darlinghurst, New South Wales
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Darlinghurst,
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2301 Erwin Road
Durham, North Carolina 27710
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Durham, NC
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New York, New York 10021
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New York, NY
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Portland, OR
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Seattle, Washington 98109
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Seattle, WA
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Tampa, FL
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