Phase 1
N=30
A Study of IXAZOMIB in Adult Patients With Lymphoma
Lymphoma
Bottom Line
View on ClinicalTrials.gov: NCT00893464 ↗Enrolled (actual)
30
Serious AEs
33.3%
Results posted
Nov 2015
Primary outcome: Primary: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) — 1; 1; 1; 1 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- IXAZOMIB (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Millennium Pharmaceuticals, Inc.
- Primary completion
- Oct 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
1; 1; 1; 1; 4; 7 | — |
| PRIMARY Number of Participants Reporting at Least 1 TEAE Related to Laboratory Assessments |
0; 0; 1; 1; 2; 4 | — |
| PRIMARY Number of Participants With Clinically Significant Change From Baseline in Vital Signs |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Maximum Tolerated Dose (MTD) |
2.34 | — |
| PRIMARY Recommended Phase 2 Dose (RP2D) |
2.34 | — |
| SECONDARY C0: Initial Plasma Concentration After Bolus Intravenous Administration |
7.430; 59.400; 106.000; NA; 713.883; 541.771 | — |
| SECONDARY AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for Ixazomib |
NA; NA; 636.8; 821.0; 1058.9; 1683.6 | — |
| SECONDARY Terminal Phase Elimination Half-life (T1/2) for Ixazomib |
292.00; 146.00; 209.39; 145.57; 107.58; 108.39 | — |
| SECONDARY Rac: Accumulation Ratio for Ixazomib |
2.174; 2.267; 2.113 | — |
| SECONDARY Ae (0-4): Amount of Drug Excreted in Urine From 0 to 4 Hours Postdose |
0; 1440; 0; NA; 8584.4; 17963.7 | — |
| SECONDARY Fe (0-4): Fraction of Dose Excreted Unchanged in Urine From 0 to 4 Hours Postdose |
0; 0.30700; 0; NA; 0.29842; 0.56896 | — |
| SECONDARY CLr: Renal Clearance |
0.000000; NA; 0.057058; 0.118686; 0.044828; 0.085303 | — |
| SECONDARY Emax: Maximum Observed Effect for Ixazomib |
5.150; 18.500; 33.200; 50.500; 66.333; 72.186 | — |
| SECONDARY TEmax: Time to Maximum Observed Effect (Emax) for Ixazomib |
0.25000; 0.08330; 0.10000; 0.08330; 0.11700; 0.08330 | — |
| SECONDARY Overall Best Response |
0; 0; 0; 0; 0; 1 | — |
Summary
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.
Eligibility Criteria
Inclusion Criteria
- Male or female patients 18 years or older.
- Eastern Cooperative Oncology Group performance status 0-2.
- 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.
- Suitable venous access for PK and pharmacodynamic evaluations.
- 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.
- Voluntary written consent must be obtained.
- 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
- Peripheral neuropathy ≥ Grade 2.
- Female patients who are lactating or have a positive serum pregnancy test during the screening period .
- Major surgery within 14 days before the first dose of treatment.
- Infection requiring systemic antibiotic therapy or other serious infection within 14 days before the first dose of study treatment.
- Life-threatening illness unrelated to cancer.
- Diarrhea > Grade 1 based on the NCI CTCAE categorization.
- Systemic antineoplastic therapy/or radiotherapy within 21 days before the first dose of study treatment.
- Systemic treatment with prohibited medications.
- Patient has symptomatic brain metastases.
- Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or myocardial infarction within the past 6 months.
- QTc > 470 milliseconds (msec) on a 12-lead electrocardiogram (ECG) obtained during the screening period.
- Known human immunodeficiency virus (HIV), hepatitis B or hepatitis C positive.
- Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
- Treatment with any investigational products within 28 days before the first dose of study treatment.
Data sourced from ClinicalTrials.gov (NCT00893464). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.