Low Dose Melphalan and Bortezomib for AML and High-Risk MDS

Inclusion Criteria

• Pathologic diagnosis of AML or high-risk MDS Patients with chronic myelomonocytic leukemia or a refractory cytopenia with multilineage dysplasia are eligible if that have one of the following criteria:
• >4 units of red blood cells transfused during the previous 3 months
• platelet count 50%
• Patients may receive prior growth factor therapy
• Patients who received prior therapies (ex. melphalan, 5-azacitidine, low-dose cytarabine) to control their MDS or AML prior to registration (Stratum 2), but are clearly nonresponders are eligible for enrollment if expected toxicity of the prior therapy has resolved
• Voluntary written informed consent
• If female, the subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study
• If male, the subject agrees to use an acceptable method for contraception for the duration of the study
• Patients that have been previously treated will be eligible for study if:
• the previous therapy was ineffective and
• all expected toxicity of the previous treatment has resolved
• In general the following guidelines regarding the elapsed time from previous treatment to eligibility should be followed
• High intensity cytotoxic treatment (7&3 induction, High Dose Ara-C): 4 weeks
• Hematopoeitic growth factors: no delay required
• Low intensity treatment (such as oral melphalan or hydrea, low dose cytarabine or 5-azacitidine) No delay required if expected toxicity has resolved and regimen ineffective

Exclusion Criteria

• AML FAB M3
• No concomitant malignancy other than a curatively treated carcinoma in situ of cervix or basal or squamous cell carcinoma of the skin
• Active, uncontrolled infections
• Chronic liver disease not due to AML, or bilirubin >2.0mg/dL
• End stage kidney disease on dialysis
• Active CNS disease. A lumbar puncture prior to treatment is not required and should not be performed in the absence of significant CNS symptoms or signs
• Patient has sensory peripheral neuropathy > grade 2 or painful peripheral neuropathy > grade 1 (see appendix A for NCI sensory neuropathy toxicity criteria) within 14 days before enrollment
• Hypersensitivity to bortezomib, boron or mannitol
• Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study