None listed
Conditions
Brief summary
The primary purpose of this trial is to assess whether the addition of venetoclax to a velcade (bortezomib), cyclophosphamide and dexamethasone treatment regime will cause an improvement in disease progression free survival. Who is it for? You may be eligible to participate in this trial if you are aged 18 years or over, have been newly diagnosed with multiple myeloma and are a candidate for chemotherapy and autologous stem cell transplant. Study details Eligible participants will be treated with 4 35 day cycles of venetoclax, velcade, cyclophosphamide and dexamethasone (V-VCD) followed by a high-dose melphalan conditioned autologous stem cell transplant (ASCT) with residual disease evaluation at day 100 post-ASCT. Participants will be required to have blood samples taken at the beginning of each cycle along with a medical exam in order for researchers to monitor whether the treatment is safe and whether it is effectively treating the myeloma. It is hoped that the findings of this trial will establish the benefits of venetoclax in combination with VCD for the treatment of multiple myeloma patients early in the course of their disease.
Interventions
Bortezomib 1.3mg/m2 subcutaneous injection days 1, 8, 15, 22 (4x 35 day cycles)
Cyclophosphamide 500mg single dose orally days 1, 8, 15, 22
Dexamethasone 40mg single dose orally days 1, 8, 15, 22
Venetoclax 800mg single dose orally taken daily on days 1 – 35
Upon completion of the four cycles of induction treatment patients then undergo high-dose (200mg/m2) melphalan conditioned autologous stem cell transplant (ASCT ), a procedure removing healthy stem cells followed by chemotherapy and then fol
Bortezomib 1.3mg/m2 subcutaneous injection days 1, 8, 15, 22 (4x 35 day cycles) Cyclophosphamide 500mg single dose orally days 1, 8, 15, 22 Dexamethasone 40mg single dose orally days 1, 8, 15, 22 Venetoclax 800mg single dose orally taken daily on days 1 – 35 Upon completion of the four cycles of induction treatment patients then undergo high-dose (200mg/m2) melphalan conditioned autologous stem cell transplant (ASCT ), a procedure removing healthy stem cells followed by chemotherapy and then followed by the transfusion of the healthy cells back into the patient, carried out as per standard of care at the participating hospital.
Sponsors
Alfred Health
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1.Male or female patients aged 18 years or older. 2.Patient has newly diagnosed treatment naïve MM as per the IMWG criteria and is planned to proceed to high-dose chemotherapy conditioned ASCT as part of first-line treatment. 3.Treatment naïve apart from a limited exposure to corticosteroids and/or radiotherapy for urgent symptom control. 4.No contraindication to the use of any of the study drugs. 5.Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. 6.Subject has measurable disease at screening, defined as at least one of the following: - Serum M-protein >= 5 g/L, OR - Urine M-protein >= 200 mg in 24-hours, OR - Serum immunoglobulin free light chain (FLC) >= 100 mg/L provided serum FLC ratio abnormal. 7.Subject must meet the following laboratory parameters, per laboratory reference range: - Absolute neutrophil count (ANC) >= 1 x 10^9/L within 2 weeks prior to starting induction. Subjects may use growth factor support to achieve ANC eligibility criteria. - Platelet count >= 50 x 109/L, within 2 weeks prior to starting induction. For subjects with > 50% myeloma involvement in the bone marrow, a platelet count of >= 30 x10^9/L within 2 weeks prior to starting induction is allowed. Subjects cannot receive a platelet transfusion within 72 hours prior to the platelet count used for eligibility. - Haemoglobin >= 80 g/L, within 2 weeks prior to starting induction. Subjects may receive RBC transfusions in accordance with institutional guidelines to meet this criterion. - Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) <= 3 × upper limit of normal range (ULN). - Total bilirubin <= 1.5 x ULN (unless bilirubin rise is due to Gilbert syndrome or of non-hepatic origin). - CrCl >= 30 mL/minute (min), measured by 24-hour urine collection or calculated using Cockcroft-Gault formula: CrCl = ((140 – age in years) × weight in kg × 0.85 if female) / (72 × serum creatinine in mg/dL) 8.Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC) prior to the initiation of any screening or study-specific procedures. 9.If female, subject is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation at least 3 months before study participation, bilateral oophorectomy and/or hysterectomy) or is of childbearing potential and is practicing an approved method of birth control throughout the study and 90 days after last dose of study drug.
Exclusion criteria
1.Subject has any of the following conditions: - Non-secretory or oligo-secretory MM. - Active plasma cell leukemia i.e., either 20% of peripheral white blood cells comprised of plasma cells or > 2.0 × 109/L) circulating plasma cells by standard differential. - Waldenström's macroglobulinemia. - Amyloidosis. - POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes). - Subject is known to be positive for Human Immunodeficiency Virus (HIV) - Significant cardiovascular disease, including uncontrolled angina, severe or uncontrolled arrhythmia, recent myocardial infarction within 6 months of induction, or congestive heart failure New York Heart Association (NYHA) Class >= 3. - Major surgery within 4 weeks prior to starting induction. - Uncontrolled and/or active systemic infections (viral, bacterial or fungal). - Chronic hepatitis B (HBV) or hepatitis C (HCV) requiring treatment. - Peripheral neuropathy >= Grade 3 or >= Grade 2 with pain within 2 weeks prior to starting induction. - Uncontrolled diabetes or uncontrolled hypertension within 14 days prior to starting induction. - Any other medical condition that, in the opinion of the Investigator, would adversely affect the subject's participation in the study. 2.Subject has a history of other active malignancies, including myelodysplastic syndrome (MDS), within the past 3 years prior to study entry, 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 - Previous malignancy with no evidence of disease, confined and surgically resected (or treated with other modalities) with curative intent and unlikely to impact survival during the duration of the study 3.Subject has a hypersensitivity or allergy to any of the components of study therapy including Venetoclax, Bortezomib, boron, mannitol, or Dexamethasone. 4.Subject has received any prior anti-MM with the exception of Dexamethasone (total dose not exceeding 160mg) or localized radiotherapy for the emergency management of newly diagnosed MM. 5.Subject has received a strong or moderate CYP3A inhibitor or inducer within 1 week prior to commencing study treatment. 6.Administration or consumption of grapefruit or grapefruit products, Seville oranges (including marmalade containing Seville orange) or star fruit within 3 days prior to the first dose of study drug.
Outcome results
None listed