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About
This phase I trial studies the side effects and best dose of hydroxychloroquine when given together with cyclophosphamide, dexamethasone, and sirolimus in treating patients with multiple myeloma that has come back after a period of improvement or does not respond to treatment. Biological therapies, such as hydroxychloroquine, may stimulate the immune system in different ways and stop cancer cells from growing. Sirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, stopping them from dividing, or by stopping them from spreading. Giving hydroxychloroquine together with sirolimus, cyclophosphamide, and dexamethasone may be a better treatment for multiple myeloma.
Full description
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of hydroxychloroquine (HCQ) in combination with rapamycin (sirolimus) and infusional cyclophosphamide and pulse dexamethasone (cy/dex) for patients with relapsed/ refractory multiple myeloma.
SECONDARY OBJECTIVES:
I. To evaluate biological activity and efficacy of the combination of cyclophosphamide, dexamethasone, rapamycin and hydroxychloroquine in patients with relapsed/refractory multiple myeloma.
II. To determine whether this treatment regimen results in mammalian target of rapamycin (mTOR) and autophagy inhibition in primary myeloma cells during therapy and if this corresponds with treatment responses.
OUTLINE: This is a dose-escalation study of hydroxychloroquine.
Patients receive hydroxychloroquine orally (PO) daily on days 1-28 (days 5-28 of course 1), sirolimus PO on days -2 to 4, and cyclophosphamide intravenously (IV) continuously and dexamethasone PO on days 1-4. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 12 months.
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Inclusion criteria
Exclusion criteria
History of allergic reactions to compounds of similar chemical or biological composition to rapamycin or hydroxychloroquine
Patients may not take any of the following medications while on study, but will be considered eligible if medication is discontinued at least 72 hours (hrs) prior to first dose of Rapamycin:
Known macular degeneration or retinopathy (diabetic or otherwise), porphyria, or psoriasis (well-controlled psoriasis allowed provided under the care of a specialist who agrees to monitor the patient for exacerbations)
Absolute neutrophil count (ANC) =< 1.0 x 10^9/L
Platelets =< 50 x 10^9/L for any reason
Serum creatinine >= 2.5 mg/dL
Total or direct bilirubin >= 2.0 mg/dL
Transaminases 2 x the upper limit of normal
Fasting glucose >= 200 mg/dL
Serum potassium < 3.4 mmol/l
Serum phosphorus < 2.4 mg/dl
Other conditions that would require therapy with hydroxychloroquine, including but not limited to, any of the following:
Evidence of other active malignancy, except:
Uncontrolled intercurrent illness including, but not limited to, any of the following:
Inability to understand or unwillingness to sign the informed consent document
Concurrent anti-myeloma therapy within:
Women of child-bearing who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 30 days after the last dose of study drug
Women who are pregnant or breastfeeding
History of G6PD deficiency
Known history of HIV infection
Primary purpose
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18 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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