Daratumumab for Multiple myeloma

Inclusion criteria

• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status ≤2.\n- 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.\n- Measurable disease confirmed by central lab at Screening, defined by at least 1 of the following: -Serum M-protein ≥1.0 g/dL (≥10 g/L), OR -Urine M-protein ≥200 mg/24 hours, OR -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.\n- Participant has received previous multiple myeloma treatment as defined in the protocol.\n- Bone marrow aspirate samples have been collected.\n- To qualify for Part 1 and 3, the participant must be t(11;14) positive as determined by an analytically validated Fluorescent In Situ Hybridization (FISH) assay per central laboratory testing.\n- Participants must have adequate hematologic, renal and hepatic function."}

Exclusion criteria

• {"criterion_text":"- Previous treatment with venetoclax or other B-Cell Lymphoma 2 (BCL-2) inhibitor\n- For participants in Parts 1 and 2: Previous treatment with daratumumab or other anti-CD38 therapy. For participants in Part 3: Prior daratumumab or other anti-CD38 antibody therapy exposure that meets ANY of the following criteria: -Failure to achieve at least a PR to most recent therapy with daratumumab or other anti-CD38 therapy. -Daratumumab or other anti-CD38 antibody therapy was discontinued due to toxicity. -Relapse within 60 days of intensive treatment (at least every other week) of daratumumab or other anti-CD38 antibody therapy. -Prior treatment with daratumumab or other anti-CD38 antibody within 6 months prior to first dose of study drug.\n- For participants in Part 2 and 3: -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. -Participant has had prior treatment with proteasome inhibitor within 60 days prior to first dose of study drug.\n- 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.\n- Treatment with anti-myeloma monoclonal antibodies within 6 weeks prior to first dose.\n- Recent corticosteroid therapy at a cumulative dose equivalent to >= 140 mg of prednisone, cumulative dose equivalent to >= 40 mg of dexamethasone, or a single dose equivalent to >= 40 mg of dexamethasone within 2 weeks prior the first dose of study drug.\n- Known central nervous system involvement of multiple myeloma.\n- Significant history of medical conditions as listed in the protocol.\n- History of other active malignancies including myelodysplatic syndromes (MDS) within the past 3 years with the exceptions of: -Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin. -Prostate cancer Gleason grade 6 or lower AND with stable Prostate Specific Antigen (PSA) levels off treatment -Previous malignancy with no evidence of disease confirmed and surgically resected (or treated with other modalities) with curative intent and unlikely to impact survival during the duration of the study.\n- Known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.\n- Has a hypersensitivity or allergy to any of the components of study therapy, excipient or boron.\n- Known allergies, hypersensitivities, or intolerance to monoclonal antibodies or human proteins, or their excipients, or known sensitivity to mammalian-derived products (see daratumumab prescribing information)."}

Primary endpoints

• {"endpoint_text":"- Overall response rate (ORR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Very good partial response (VGPR) or better rate","definition_or_measurement_approach":""}
• {"endpoint_text":"- Complete response (CR) or better rate","definition_or_measurement_approach":""}
• {"endpoint_text":"- Time to response (TTR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Duration of response (DOR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Time to progression (TTP)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Progression-free survival (PFS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- Minimal Residual Disease (MRD)","definition_or_measurement_approach":"Assess MRD in the bone marrow by next generation sequencing (NGS) (as stated in secondary objectives)."}
• {"endpoint_text":"- Safety, Pharmacokinetic (PK) and Biomarker Research Variables","definition_or_measurement_approach":"Includes evaluation of safety profiles; characterize pharmacokinetic (PK) profile of venetoclax and daratumumab when administered as VenDd or VenDVd and characterize immunogenicity to daratumumab when administered with venetoclax (as stated in secondary objectives)."}

Denmark

Latest Decision Or Authorization Date

24-05-2024

Number Of Sites

3

Number Of Participants

9

France

Latest Decision Or Authorization Date

17-06-2024

Number Of Sites

5

Number Of Participants

8

Germany

Latest Decision Or Authorization Date

21-06-2024

Number Of Sites

1

Number Of Participants

1

Primary sponsor

Full Name

AbbVie Deutschland GmbH & Co. KG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Contract research organisations

Name

Parexel International Corp.

Responsibilities

Ancillary Supplies

Name

Medidata Solutions Inc.

Responsibilities

Clinical data management / technology (coded duty: 7)

Name

Endpoint Clinical Inc.

Responsibilities

CRO services (coded duty: 3)

Third parties

• {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"Ancillary Supplies","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"code:7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Abbott Molecular Inc.","duties_or_roles":"MRD Samples","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Flagship Biosciences Inc.","duties_or_roles":"Immunophenotyping","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"code:3","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"ADA/NAb/PK analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Hematogenix Laboratory Services Limited","duties_or_roles":"EU BMA Fish, Optional end of treatment BMA FISH","organisation_type":"Laboratory/Research/Testing facility"}