Clinical trial NCT00893464: A Study of IXAZOMIB in Adult Patients With Lymphoma
Official title: An Open-Label, Dose-Escalation, Phase 1 Study of IXAZOMIB (MLN9708), A Second-Generation Proteasome Inhibitor, in Adult Patients With Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma
Lead sponsor: Millennium Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2009-05-06
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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:

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.

Primary outcomes:
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 30 days after last dose of study drug
measure: Number of Participants Reporting at Least 1 TEAE Related to Laboratory Assessments
timeFrame: Baseline and Days 1, 8, and 15 of each treatment cycle (up to Cycle 45)
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
timeFrame: Baseline and Days 1, 8, 15 of each treatment cycle up to 45 treatment cycles
measure: Maximum Tolerated Dose (MTD)
timeFrame: Treatment Cycle 1
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: Baseline up to Treatment Cycle 45
Secondary outcomes:
measure: C0: Initial Plasma Concentration After Bolus Intravenous Administration
timeFrame: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 336 hours postdose)
measure: AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for Ixazomib
timeFrame: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
measure: Terminal Phase Elimination Half-life (T1/2) for Ixazomib
timeFrame: Cycle 1 Day 15: Predose and at multiple time points (up to 336 hours postdose)
measure: Rac: Accumulation Ratio for Ixazomib
timeFrame: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
measure: Ae (0-4): Amount of Drug Excreted in Urine From 0 to 4 Hours Postdose
timeFrame: Cycle 1, Days 1 and 15: 0 to 4 hours postdose
measure: Fe (0-4): Fraction of Dose Excreted Unchanged in Urine From 0 to 4 Hours Postdose
timeFrame: Cycle 1, Days 1 and 15: 0 to 4 hours postdose
measure: CLr: Renal Clearance
timeFrame: Cycle 1, Days 1 and 15: 0 to 4 hours postdose
measure: Emax: Maximum Observed Effect for Ixazomib
timeFrame: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
measure: TEmax: Time to Maximum Observed Effect (Emax) for Ixazomib
timeFrame: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
measure: Overall Best Response
timeFrame: Baseline up to Cycle 45
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Tower Cancer Research Center
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Westwood
country: United States
facility: Kansas University Medical Center
state: Kansas
city: New York City
country: United States
facility: Cornell University
state: New York
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Madison
country: United States
facility: University of Wisconsin Madison
state: Wisconsin
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References: