A Phase 2 Clinical Trial of Dichloroacetate in Plateau Phase Myeloma - DiCAM
In 'plateau phase' myeloma patients does 3 months of oral dichloroacetate lead to a reduction in residual disease burden as assessed by serum paraprotein or light chain levels.
Department of Haematology - Capital Region Cancer Services- The Canberra Hospital
25 participants
May 28, 2015
Interventional
Conditions
Summary
This study aims to determine whether 3 months of treatment with oral dichloroacetate can supress multiple myeloma. Who is it for? You may be eligible to join this study if you are aged 18 years or above and have a diagnosis of Plasma Cell Myeloma which is in a 'Plateau-Phase', i.e. a period of neither progression nor response at least 28 days following the last change in myeloma treatment. Study details: All participants in this study will be treated with a drug called dichloroacetate. This will be taken orally (by mouth) daily for 3 months A number of blood samples will be taken throughout treatment in order to determine how the body responds to treatment. This information will help us determine how well dichloroacetate is tolerated, and whether it has the ability to suppress multiple myeloma.
Eligibility
Inclusion Criteria18
- Diagnosis of Plasma Cell Myeloma (at any time) according to WHO criteria
- Aged 18 years or older
- Eastern Co- operative Oncology Group Performance status less than 2
- Life expectancy due to myeloma or co- morbid conditions in the opinion of the treating physician likely to exceed 3 months
- AND
- has measurable residual disease i.e.
- Quantifiable serum paraprotein on electrophoresis at least 1g/L OR
- Elevated free kappa (>21mg/L) or lambda light chains (>30mg/L) AND a minimum difference between level of involved/uninvolved light chain of 150mg/L AND an abnormal serum free light chain ratio (normal range = 0.26-1.26)
- AND
- is in a ‘Plateau- Phase’ i.e.
- A period of neither progression nor response at least 28 days following the last change in myeloma treatment
- Progression defined as per IWMG
- an increase in the paraprotein by >= 25% and at least 5g/L
- In light chain only patients, >25% increase in difference between involved and uninvolved light chain level, with an absolute increase of >0.1g/L
- development of new lytic lesions
- development of new end organ damage (Renal disease, marrow failure, lytic lesions, hypercalcaemia) attributable to myeloma or new plasmacytomas
- Response defined as reduction in the paraprotein by at least 25% OR in the case of light chain only myeloma, at least 25% decrease in the difference between the involved and uninvolved light chain and an absolute reduction of at least 100mg/L.
- Blood samples to assess for plateau phase must be at least 28 days apart
Exclusion Criteria27
- Unable to give informed consent
- Non-secretory myeloma
- Receipt of any active anti-myeloma therapy (excluding bisphosphonates) in the 16 weeks prior to enrolment, with the exception that patients on stable doses of long- term maintenance therapy will be allowed (no dose alteration in the prior 8 weeks).
- Pregnant or breastfeeding
- Unwilling to avoid pregnancy and use birth control (if applicable) during the study and for 4 weeks after completion of the study
- Unable to swallow capsules
- Major surgery within the last 28 days
- Enrolled in another trial or have discontinued from another clinical trial within the last 14 days
- Any serious pre-existing medical condition that, in the opinion of the study doctor would keep you from being on this trial
- Any peripheral motor or sensory neuropathy, neuralgia or paraesthesia (of grade 3 or worse)
- Any pre-existing severe ataxia or tremor (grade 3 or worse)
- Known history of liver disease (cirrhosis established by imaging studies or biopsy) or abnormal liver function tests within the last 14 days (AST or ALT > 3 x ULN or ALP >2.5 x ULN or total bilirubin > 1.5 x ULN)
- Any more than moderate renal impairment i.e. Calculated Creatinine Clearance by Cockcroft Gault formula of greater than or equal to 30 mL/min
- Inadequate cardiac function defined as:
- Electrocardiographic (ECG) evidence of
- Acute ischemia
- Active clinically significant conduction system abnormalities
- >Grade 2 (>480 ms) (QTc) prolongation
- Uncontrolled angina or severe ventricular arrhythmias
- Myocardial infarction within the last 6 months
- Class 3 or higher New York Heart Association Congestive Heart Failure
- Haematological
- Haemoglobin < 80g/L
- Absolute Neutrophil Count (ANC) less than 1.0 x 10^9/L
- Platelet Count less than 50 x 10^9/L
- Any active fungal, bacterial and/or known active viral infection including HIV or hepatitis (A, B, or C).
- A second malignancy which in the opinion of the investigator may affect the interpretation of results
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Interventions
Oral Dichloroacetate as the sodium salt, administered by mouth for 3 months. Dose will be 25mg/kg twice daily loading for 3 days then reduce to 6.25mg/kg twice daily. A single boost of 25mg/kg on day 8 will occur followed by return to maintenance dose of 6.25mg/kg twice daily. Adherence monitoring will be by capsule count with dispensing of new medication as well as pharmacokinetic monitoring of plasma levels.
Locations(1)
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ACTRN12615000226505