A Study of IXAZOMIB in Adult Patients With Lymphoma

An Open-Label, Dose-Escalation, Phase 1 Study of IXAZOMIB (MLN9708), A Second-Generation Proteasome Inhibitor, in Adult Patients With Lymphoma

This study is an open-label, multicenter, phase 1, dose-escalation study of IXAZOMIB in adult patients with lymphoma. This study will be the first to administer IXAZOMIB to patients with lymphoma.

Inclusion Criteria:

1. Male or female patients 18 years or older.

2. Eastern Cooperative Oncology Group performance status 0-2.

3. Patients must have a confirmed diagnosis of lymphoma that is relapsed and/or refractory after at least 2 prior chemotherapeutic regimens and for which no curative option exists. Patients with Waldenstrom's macroglobulinemia are not eligible for enrollment in this study. Patients with Hodgkin lymphoma are considered eligible for this study.

4. Suitable venous access for PK and pharmacodynamic evaluations.

5. Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse.

   Male patients who agree to to practice 2 effective methods of contraception or abstain from heterosexual intercourse.

6. Voluntary written consent must be obtained.

7. Adequate blood and chemistry values during the screening period:

   • Absolute neutrophil count (ANC) ≥ 1,500/mm3; platelet count ≥ 100,000/mm3.
   • Total bilirubin must be ≤ 1.5 × the upper limit of the normal range upper limit of normal (ULN).
   • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be ≤ 2.5 × the upper limit of normal (ULN). AST and ALT may be elevated up to 5 times the upper limit of normal if their elevation can be reasonably ascribed to the presence of metastatic disease.
   • Calculated creatinine clearance ≥ 30 mL/minute.

Exclusion Criteria:

1. Peripheral neuropathy ≥ Grade 2.
2. Female patients who are lactating or have a positive serum pregnancy test during the screening period .
3. Major surgery within 14 days before the first dose of treatment.
4. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before the first dose of study treatment.
5. Life-threatening illness unrelated to cancer.
6. Diarrhea > Grade 1 based on the NCI CTCAE categorization.
7. Systemic antineoplastic therapy/or radiotherapy within 21 days before the first dose of study treatment.
8. Systemic treatment with prohibited medications.
9. Patient has symptomatic brain metastases.
10. Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or myocardial infarction within the past 6 months.
11. QTc > 470 milliseconds (msec) on a 12-lead electrocardiogram (ECG) obtained during the screening period.
12. Known human immunodeficiency virus (HIV), hepatitis B or hepatitis C positive.
13. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
14. Treatment with any investigational products within 28 days before the first dose of study treatment.