venetoclax for Relapsed or refractory multiple myeloma | t(11;14)-positive multiple myeloma

Stratification factors

• Age at randomization (<65 versus ≥65)
• Prior lines of therapy (2 to 3 versus 4 or more)
• International Staging System (ISS) Stage at screening (I versus II versus III)

Inclusion criteria

• {"criterion_text":"- Subjects must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures."}
• {"criterion_text":"- Subjects should have laboratory values meeting the following criteria within the screening period prior to the first dose of study drug: Absolute neutrophil count (ANC) ≥1000/μL; subject may use growth factor support to achieve ANC eligibility criteria; Platelets: ≥50,000/mm3. For subjects with > 50% myeloma involvement in the marrow, a platelet count of ≥30,000 mm3. Subjects may not have received a platelet transfusion within 72 hours prior to the platelet count used for eligibility; Hemoglobin ≥8.0 g/dL; subject may receive red blood cell (RBC) transfusions in accordance with institutional guidelines to meet this criteria; AST and ALT ≤3 × upper limit of normal (ULN); Total bilirubin ≤1.5 x ULN (subjects with documented Gilbert's syndrome, may have bilirubin > 1.5 × ULN); Creatinine clearance ≥30 mL/min, measured by 24-hour urine collection or calculated using the Cockcroft-Gault formula); Serum calcium corrected for albumin ≤14.0 mg/dL (≤3.5 mmol/L) or ionized calcium (≤6.5mg/dL (≤1.6mmol/L)."}
• {"criterion_text":"- Subjects should be willing or able to comply with procedures required in this protocol."}
• {"criterion_text":"- Subjects should be willing and able to receive antithrombotic prophylactic treatment."}
• {"criterion_text":"- Documented diagnosis of multiple myeloma based on standard IMWG criteria."}
• {"criterion_text":"- Subject has an ECOG performance status ≤ 2"}
• {"criterion_text":"- Subject has documented disease progression on or within 60 days of completion of their last therapy."}
• {"criterion_text":"- Subject has received at least 2 prior lines of therapy. A line of therapy consists of at least 1 complete cycle of a single agent, a regimen consisting of a combination of several drugs, or a planned sequential therapy of various regimens."}
• {"criterion_text":"- Subjects must not be incarcerated and must be freely willing and able to provide informed consent (e.g., adults under legal protection measure [e.g., under guardianship/curatorship] or unable to express their consent and select adults under psychiatric care). Investigator's discretion should be applied."}
• {"criterion_text":"- Subject must have received at least 2 consecutive cycles of lenalidomide and be relapsed/refractory to lenalidomide as defined by one of the following: Subject experienced PD on or within 60 days of completing treatment. Subject exhibited PR or better but relapsed within 6 months after stopping treatment."}
• {"criterion_text":"- Subject must have received at least 2 consecutive cycles of a proteasome inhibitor (bortezomib, carfilzomib or ixazomib)."}
• {"criterion_text":"- Subject has measurable disease at Screening, defined by at least 1 of the following: Serum M-protein ≥0.5 g/dL (≥5 g/L); OR Urine M-protein ≥200 mg/24 hours; OR Involved serum immunoglobulin free light chain (FLC) ≥10 mg/dL (100 mg/L), provided serum FLC ratio is abnormal"}
• {"criterion_text":"- Subject has MM positive for t(11;14) as determined by an analytically validated FISH assay per centralized laboratory testing."}
• {"criterion_text":"- A negative serum pregnancy test for all female subjects (except those of non-childbearing potential) within 10 to 14 days prior to initiating therapy and a negative urine pregnancy test within 24 hours for all female subjects (except those of non-childbearing potential) at baseline prior to the first dose of study drug."}
• {"criterion_text":"- If female, subject must be either postmenopausal, OR permanently surgically sterile OR for women of childbearing potential practicing at least 2 protocol-specified methods of birth control that are effective from at least 30 days before starting study drugs through at least 30 days after the last dose of any study drug."}
• {"criterion_text":"- If male, and subject is sexually active with female partner(s) of childbearing potential, he must agree, from Study Day 1 through 30 days after the last dose of study drug, to practice the protocol-specified contraception."}
• {"criterion_text":"- Adult male or female subjects ≥18 years old."}

Exclusion criteria

• {"criterion_text":"- Subject has history of treatment with venetoclax or another BCL-2 inhibitor or pomalidomide."}
• {"criterion_text":"- Female who is pregnant, breastfeeding, or considering becoming pregnant during the study and for at least 30 days after the last dose of study drug."}
• {"criterion_text":"- Male who is considering fathering a child or donating sperm and/or semen during the study and for at least 30 days after the last dose of study drug."}
• {"criterion_text":"- Subject who have been treated with any systemic anti-myeloma therapies within 5 half-lives or 2 weeks prior to randomization, whichever is longer (or 2 weeks if half-life unknown), and through the last dose of any study drug."}
• {"criterion_text":"- Subject who have been treated with anti-myeloma radiotherapy within 2 weeks prior to randomization."}
• {"criterion_text":"- Subject who have received corticosteroid therapy at a dose equivalent to > 4 mg daily of dexamethasone or a single dose of corticosteroid equivalent dose > 40 mg of dexamethasone within 2 weeks prior to randomization."}
• {"criterion_text":"- Subject who have used systemic strong or moderate inhibitor or inducer of cytochrome P450 (CYP) 3A within 1 week prior to the first dose of study drugs."}
• {"criterion_text":"- Subject who have used systemic strong inhibitor of CYP1A2 within 1 week prior to first dose."}
• {"criterion_text":"- Subject who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or starfruit within 3 days prior to first dose."}
• {"criterion_text":"- Subject who anticipate the use of prohibited medications or foods during study participation."}
• {"criterion_text":"- Subject has a history of other active malignancies, including myelodysplastic syndromes (MDS), within the past 3 years with the following exceptions: Adequately treated in situ carcinoma of the cervix uteri or the breast; 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; or Previous malignancy with no current evidence of disease, and which was confined and surgically resected (or treated with other modalities) with curative intent and unlikely to impact survival during the duration of the study."}
• {"criterion_text":"- Subject has evidence of ongoing graft-versus-host disease (GvHD) if prior stem cell transplant (SCT)."}
• {"criterion_text":"- Subject must not have received any live vaccines within 8 weeks prior to randomization"}
• {"criterion_text":"- Subject has had prior treatment with the following: Allogeneic or syngeneic SCT within 16 weeks prior to randomization; or Autologous SCT within 12 weeks prior to randomization"}
• {"criterion_text":"- Subject has known central nervous system involvement of multiple myeloma."}
• {"criterion_text":"- Subject has a history of clinically significant renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular, pulmonary or hepatic disease within the last 6 months that, in the opinion of the investigator, would adversely affect participation in this study."}
• {"criterion_text":"- Subject has a history of known allergies, hypersensitivities, or intolerance to any of the study drug or excipients, or thalidomide derivatives."}
• {"criterion_text":"- Subject has the following conditions: Nonsecretory multiple myeloma; Active plasma cell leukemia i.e., either 20% of peripheral white blood cells or > 2.0 × 109/L circulating plasma cells by standard differential; Waldenström's macroglobulinemia; Primary amyloidosis; POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes); Known human immunodeficiency virus (HIV) infection; Active hepatitis B (hepatitis B surface antigen [HBsAg] positive) or C infection based on screening central laboratory blood testing at screening; Significant cardiovascular disease, including uncontrolled angina, arrhythmia, recent myocardial infarction within 6 months prior to first dose, congestive heart failure NYHA Class ≥3; Major surgery within 4 weeks prior to first dose or planned during study participation; Acute infections within 14 days prior to first dose requiring therapy (antibiotic, antifungal, or antiviral); Uncontrolled diabetes or hypertension within 14 days prior to first dose; or Peripheral neuropathy ≥Grade 3 or ≥Grade 2 with pain within 2 weeks prior to first dose."}

Primary endpoints

• {"endpoint_text":"- The primary efficacy endpoint is progression-free survival (PFS) per Independent Review Committee (IRC) based on IMWG criteria. PFS is defined as the time in days from subject randomization to the date of the first documented progressive disease (PD) or death due to any cause, whichever occurs first.","definition_or_measurement_approach":"PFS per IRC based on IMWG criteria; defined as time in days from randomization to first documented PD or death from any cause."}

Secondary endpoints

• {"endpoint_text":"- Overall response rate (ORR) per the independent review committee (IRC)","definition_or_measurement_approach":"ORR assessed by IRC."}
• {"endpoint_text":"- Rate of very good partial response (VGPR) or better per the IRC","definition_or_measurement_approach":"VGPR or better rate assessed by IRC per IMWG criteria."}
• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":"OS measured as time from randomization to death from any cause."}
• {"endpoint_text":"- Minimal residual disease (MRD) negativity rate","definition_or_measurement_approach":"MRD negativity rate assessed using MRD testing (details in protocol)."}
• {"endpoint_text":"- Time to deterioration in disease symptoms as measured by the disease symptom domain of the EORTC QLQ-MY20","definition_or_measurement_approach":"Time to deterioration measured by the disease symptom domain of EORTC QLQ-MY20."}
• {"endpoint_text":"- Time to deterioration in physical functioning as measured by the physical functioning domain of EORTC QLQ-C30","definition_or_measurement_approach":"Time to deterioration measured by physical functioning domain of EORTC QLQ-C30."}
• {"endpoint_text":"- Other Patient reported outcomes (PROs) assessed using Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7a, Brief Pain Inventory –Short Form [(BPI-SF]), EuroQoL 5 Dimension 5 Level (EQ5D5L) and remaining domains of EORTC QLQ-MY20, and EORTC QLQ-C30 survey instruments","definition_or_measurement_approach":"PROs assessed using PROMIS Fatigue SF-7a, BPI-SF, EQ5D5L, EORTC QLQ-MY20 and EORTC QLQ-C30 instruments."}
• {"endpoint_text":"- Duration of response (DOR)","definition_or_measurement_approach":"DOR measured from first documented response to progression or death."}
• {"endpoint_text":"- Time to disease progression (TTP)","definition_or_measurement_approach":"TTP measured per IMWG criteria."}
• {"endpoint_text":"- Time to response (TTR)","definition_or_measurement_approach":"TTR measured as time from randomization to first documented response."}
• {"endpoint_text":"- Pharmacokinetics of venetoclax","definition_or_measurement_approach":"PK of venetoclax assessed through specified PK sampling and analyses."}
• {"endpoint_text":"- Safety","definition_or_measurement_approach":"Safety assessed by adverse event reporting, labs, and other safety assessments."}

Czechia

Earliest CTIS Part Ii Submission Date

06-12-2023

Latest Decision Or Authorization Date

15-01-2024

Processing Time Days

40

Number Of Sites

5

Number Of Participants

11

Italy

Earliest CTIS Part Ii Submission Date

06-12-2023

Latest Decision Or Authorization Date

12-01-2024

Processing Time Days

37

Number Of Sites

6

Number Of Participants

15

France

Earliest CTIS Part Ii Submission Date

06-12-2023

Latest Decision Or Authorization Date

10-01-2024

Processing Time Days

35

Number Of Sites

7

Number Of Participants

10

Denmark

Earliest CTIS Part Ii Submission Date

06-12-2023

Latest Decision Or Authorization Date

10-01-2024

Processing Time Days

35

Number Of Sites

4

Number Of Participants

6

Spain

Earliest CTIS Part Ii Submission Date

06-12-2023

Latest Decision Or Authorization Date

11-01-2024

Processing Time Days

36

Number Of Sites

9

Number Of Participants

16

Greece

Earliest CTIS Part Ii Submission Date

06-12-2023

Latest Decision Or Authorization Date

23-02-2024

Processing Time Days

79

Number Of Sites

3

Number Of Participants

14

Germany

Earliest CTIS Part Ii Submission Date

06-12-2023

Latest Decision Or Authorization Date

11-01-2024

Processing Time Days

36

Number Of Sites

1

Number Of Participants

19

Primary sponsor

Full Name

AbbVie Deutschland GmbH & Co. KG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Contract research organisations

Name

Endpoint Clinical Inc.

Responsibilities

code 3

Name

Medidata Solutions Inc.

Responsibilities

code 7

Name

Signant Health Management Limited

Responsibilities

code 7

Name

Cytel Inc.

Responsibilities

Data Monitoring Committee

Name

Perceptive Informatics Inc.

Responsibilities

Medical image analysis/ review - X-ray, MRI, ultrasound, etc.

Name

Labcorp Central Laboratory Services S.a.r.l.

Responsibilities

Processing and analysing efficacy results such as serum and urine M-Protein and Free-Light Chains

Name

Hematogenix Laboratory Services Limited

Responsibilities

EU FISH Testing

Name

NeoGenomics Europe S.A.

Responsibilities

EU FISH Testing

Third parties

• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"code 3","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Hematogenix Laboratory Services Limited","duties_or_roles":"EU FISH Testing","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"code 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Cytel Inc.","duties_or_roles":"Data Monitoring Committee","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Switzerland","full_name":"NeoGenomics Europe S.A.","duties_or_roles":"EU FISH Testing","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Signant Health Management Limited","duties_or_roles":"code 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services S.a.r.l.","duties_or_roles":"Processing and analysing efficacy results such as serum and urine M-Protein and Free-Light Chains","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"Medical image analysis/ review - X-ray, MRI, ultrasound, etc.","organisation_type":"Pharmaceutical company"}