Clinical Drug Experience Knowledgebase

Criteria

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 <50,000/uL
absolute neutrophil count <1000/uL and a recent infection requiring antibiotics
Patients may either be considered to be poor candidates for standard induction chemotherapy based on reasonable medical evidence or have declined such therapy, but still desire palliative treatment beyond that of best supportive care
Primary refractory disease or have disease that has relapsed after prior cytoxic therapy
Karnofsky performance status of >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