A Phase I/II Trial of Hydroxychloroquine Added to Bortezomib for Relapsed/Refractory Myeloma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed multiple myeloma

- Must meet 1 of the following criteria:

- Relapsed disease documented

- Disease refractory to at least one prior treatment regimen (may include
autologous and allogeneic bone marrow transplantation)

- In need of further therapy for myeloma, as determined by the patient's treating
physician

- No known CNS involvement

- Calvarial lytic lesions or plasmacytomas are not exclusion criteria if there is
no CNS involvement

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Life expectancy ≥ 3 months

- Absolute neutrophil count ≥ 500/μL

- Hemoglobin ≥ 7 g/dL (with or without transfusion support)

- Platelets ≥ 25,000/μL (with or without transfusion support)

- Total bilirubin ≤ 2 x upper limit of normal (ULN)

- AST/ALT ≤ 2.5 x ULN

- Creatinine ≤ 2 times ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception prior to and during study treatment

- No baseline peripheral neuropathy ≥ grade 2

- No history of allergic reactions to compounds of similar chemical or biological
composition to bortezomib or hydroxychloroquine

- No 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

- No other conditions that would require therapy with hydroxychloroquine, including but
not limited to, any of the following:

- Systemic lupus

- Rheumatoid arthritis

- Porphyria cutanea tarda

- Malaria treatment or prophylaxis

- No concurrent or prior malignancy except for the following:

- Basal cell or squamous cell carcinoma of the skin

- Treated carcinoma in situ

- Localized prostate adenocarcinoma (stage T1a or T1b) with a stable PSA for a
period of at least 4 months allowed

- Patients with a prior malignancy treated with chemotherapy, biologic agents,
and/or radiation are eligible for this study if they have completed therapy ≥ 4
years previously with no evidence of recurrent disease

- Patients with a prior malignancy treated with surgery alone are eligible for
this study if they have completed therapy ≥ 2 years previously with no evidence
of recurrent disease

- No uncontrolled intercurrent illness including, but not limited to, any of the
following:

- Uncontrolled ongoing infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness or social situations that would limit compliance with study
requirements

- No prior dose-limiting toxicity due to bortezomib administration

- No inability to understand or unwillingness to sign the informed consent document

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- At least 7 days since prior corticosteroids

- At least 14 days since prior antimyeloma agents, including thalidomide or
lenalidomide

- Concurrent therapy with bisphosphonates allowed at the discretion of the treating
physician

- Concurrent hematopoietic growth factors allowed, including filgrastim (G-CSF) or
pegfilgrastim, epoetin alpha, and darbepoetin alpha

- Concurrent participation in non-treatment studies allowed, if it will not interfere
with participation in this study

- No concurrent radiotherapy except local radiotherapy during the treatment phase of
this study for palliation of pain or prevention of fracture

- No concurrent treatment with a different investigational regimen

- No concurrent therapy with other anticancer agents

- No concurrent participation in other investigational trials that involve novel
therapies