None listed
Conditions
Brief summary
This study aims to investigate the safety and tolerability of Hydroxychloroquine in combination with Carfilzomib and Dexamethasone for multiple myeloma. Who is it for? You may be eligible for this study if you are a patient aged over 18 years who has a diagnosis of relapsed or refractory multiple myeloma patients with a partial response or less after 2 cycles of Carfilzomib treatment. Study details Participants will undergo 2 cycles of once-weekly Carfilzomib and Dexamethasone as per the standard of care. If participants are deemed to have a partial response or less by clinician assessment, Hydroxycholoroquine treatment will be initiated for the next 10 cycles alongside continuing Carfilzomib and Dexamethasone. Data on adverse events, toxicities and dose limiting toxicities as well as disease response will be collected. It is hoped that data from this study will help to inform the role of Hydroxychloroquine in treating multiple myeloma.
Interventions
All study participants will initially receive 2 cycles of once-weekly intravenous Carfilzomib and oral Dexamethasone as per the standard of care. During the rest period of Cycle 2, disease response assessment will be performed according to the International Myeloma Working Group (IMWG) Criteria for Response Assessment. Each cycle is 28 days.
Participants who achieve a very good partial response (VGPR) or above will continue receiving once-weekly Carfilzomib and Dexamethasone (without Hydroxychlo
All study participants will initially receive 2 cycles of once-weekly intravenous Carfilzomib and oral Dexamethasone as per the standard of care. During the rest period of Cycle 2, disease response assessment will be performed according to the International Myeloma Working Group (IMWG) Criteria for Response Assessment. Each cycle is 28 days. Participants who achieve a very good partial response (VGPR) or above will continue receiving once-weekly Carfilzomib and Dexamethasone (without Hydroxychloroquine), as per the standard of care and at the discretion of the treating physician. Participants who achieve a partial response (PR) or below will undergo additional assessments before beginning treatment with oral Hydroxychloroquine and continued once-weekly Carfilzomib and Dexamethasone. The dose of Hydroxychloroquine that a participant will receive is dependent on the stage of dose-escalation: Level -1, 200 mg every other day; level 1 (starting dose) 200 mg once daily; level 2, 200 mg twice daily; level 3, 200 mg three times daily; level 4, 400 mg twice daily. The duration of combined treatment will be a maximum of 10 cycles. Carfilzomib 20 mg/m2 will be given as the starting dose on Cycle 1 Day 1, followed by escalation to 70 mg/m2 for all subsequent doses, if tolerated. Participants will continue to receive Carfilzomib at 70 mg/m2 until treatment discontinuation. Strategies to monitor adherence include checking patient records, medication diary and counting hydroxychloroquine tablets at the end of each cycle.
Sponsors
South Western Sydney Local Health District
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
• Written informed consent given by the participant or next of kin, legal guardian or appointed public guardian • Males and females aged greater than 18 • Disease status: Progressive multiple myeloma according to the IMWG Criteria for Response Assessment after at least one prior line of therapy and satisfies the PBS criteria for Carfilzomib treatment • Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 • Left ventricular ejection fraction greater than or equal to 40%, assessed by echocardiogram or multi-gated acquisition scan • Absolute neutrophil count greater than or equal to 1 x 109/L within 21 days prior to Cycle 1 Day 1 • Haemoglobin greater than or equal to 80 g/L within 21 days prior to Cycle 1 Day 1 • Platelet count greater than or equal to 50 x 109/L (or greater than or equal to 30 x 109/L if myeloma involvement in the bone marrow is greater than 50%), within 21 days prior to Cycle 1 day 1 • Calculated or measured creatinine clearance of greater than or equal to 15 mL/min within 21 days prior to Cycle 1 Day 1 • Adequate hepatic function within 21 days prior to Cycle 1 Day 1, with bilirubin < 1.5 times the upper limit of normal, and aspartate aminotransferase and alanine aminotransferase < 3 times the upper limit of normal. • Female patients of child-bearing potential must have a negative serum pregnancy test within 21 days prior to Cycle 1 Day 1 and agree to use an effective method of contraception during the study and for 3 months following the last dose of drug o Postmenopausal females (> 45 years old and without menses for > 1 year) and surgically sterilised females are exempt from any pregnancy test. • Male patients must agree to use an effective method of contraception during the study and for 3 months following the last dose of drug
Exclusion criteria
• Written informed consent not obtained • ECOG performance status greater than or equal to 2 • Known hypersensitivity to 4-aminoquinoline compounds or Hydroxychloroquine • Known hypersensitivity to sulfobutyl betadex sodium (a cyclodextrin used to solubilise Carfilzomib) • G6PD deficiency • Pre-existing maculopathy of the eye • Currently on a clinical trial for any other anti-cancer drug or anti-myeloma chemotherapy • Has active congestive heart failure (New York Heart Association Functional Classification of Heart Failure Class III to IV, symptomatic ischaemia or conduction abnormalities uncontrolled by conventional intervention • Has had myocardial infarction within 4 months prior to Cycle 1 Day 1 • Prolonged QT interval on electrocardiogram • Pre-existing proarrhythmic conditions (e.g., bradycardia < 50 bpm) • Any history of ventricular dysrhythmia • Uncorrected hypokalaemia and/or hypomagnesaemia • Uncontrolled hypertension (greater than or equal to 140/90 mmHg within 21 days prior to Cycle 1 Day 1) • Platelet count < 50 x 109/L and neutrophil count < 0.5 x 109/L (except in patients with cytopenia thought to be attributed to multiple myeloma) • Currently pregnant or lactating • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes) • Waldenstrom macroglobulinemia • Second malignancy within the past 3 years except the following: o Adequately treated basal cell or squamous cell skin cancer o Carcinoma in situ of the cervix o Prostate cancer with Gleason score < 6 and stable prostate-specific antigen over 12 months o Breast carcinoma in situ with full surgical resection o Treated medullary or papillary thyroid cancer • Has myelodysplastic syndrome • Chemotherapy with approved or investigational anticancer therapeutics within 7 days prior to screening bone marrow biopsy • Glucocorticoid therapy (prednisolone > 30 mg/day or equivalent) within 7 days prior to screening bone marrow biopsy • Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to screening bone marrow biopsy and Cycle 1 Day 1 (i.e., prior radiation must have been to < 30% of bone marrow) • Immunotherapy within 21 days prior to screening bone marrow biopsy and Cycle 1 Day 1 • Major surgery (excluding kyphoplasty) within 14 days prior to screening bone marrow biopsy and Cycle 1 Day 1 • Acute active infection requiring systemic antibiotics, antiviral (except antiviral therapy directed at hepatitis B) or antifungal agents within 7 days prior to screening bone marrow biopsy and Cycle 1 Day 1 • Known HIV seropositive, hepatitis C infection (except for patients who have had hepatitis C treatment and have cleared blood hepatitis C viral RNA) and/or hepatitis B (except for patients with hepatitis B surface antigen or core antibody receiving and responding to antiviral therapy directed at hepatitis B) • Known cirrhosis • Ongoing graft-vs-host disease • Taking any prohibited concomitant medication that cannot be stopped for the duration of the study • Any other clinically significant medical condition or psychiatric condition (in the investigator’s opinion) that may interfere with protocol adherence or a patient’s ability to give or withdraw informed consent • Any other diseases, clinical features and laboratory abnormalities that contraindicates the use of investigational drug and /or renders the participant at high risk of complications.
Outcome results
None listed