Safety and Tolerability of Hydroxychloroquine in Participants with Multiple Myeloma and Partial Response or Less to Carfilzomib
- Conditions
- CancerMyelomaCancer - Myeloma
- Registration Number
- ACTRN12621001458820
- Lead Sponsor
- South Western Sydney Local Health District
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot yet recruiting
- Sex
- All
- Target Recruitment
- 36
•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
oPostmenopausal 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
•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:
oAdequately treated basal cell or squamous cell skin cancer
oCarcinoma in situ of the cervix
oProstate cancer with Gleason score < 6 and stable prostate-specific antigen over 12 months
oBreast carcinoma in situ with full surgical resection
oTreated 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method