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A Study of IXAZOMIB in Adult Patients With Lymphoma

12. října 2015 aktualizováno: Millennium Pharmaceuticals, Inc.

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.

Přehled studie

Postavení

Dokončeno

Podmínky

Intervence / Léčba

Typ studie

Intervenční

Zápis (Aktuální)

31

Fáze

  • Fáze 1

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

  • Kanada
    • Quebec
      • Montreal, Quebec, Kanada, H3T 1E2
        • Jewish General Hospital
  • Spojené státy
    • California
      • Beverly Hills, California, Spojené státy, 90211
        • Tower Cancer Research Center
    • Colorado
      • Denver, Colorado, Spojené státy, 80218
        • Rocky Mountain Cancer Center
    • Kansas
      • Westwood, Kansas, Spojené státy, 66160
        • Kansas University Medical Center
    • New York
      • New York City, New York, Spojené státy, 10021
        • Cornell University
    • Pennsylvania
      • Philadelphia, Pennsylvania, Spojené státy, 19107
        • Thomas Jefferson University
    • Wisconsin
      • Madison, Wisconsin, Spojené státy, 53792
        • University of Wisconsin Madison

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

18 let a starší (Dospělý, Starší dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

Popis

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.

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: N/A
  • Intervenční model: Přiřazení jedné skupiny
  • Maskování: Žádné (otevřený štítek)

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: IXAZOMIB
Lék: IXAZOMIB
Patients will be administered IXAZOMIB by IV on Days 1, 8, and 15 of a 28-day cycle. The first stage of the study will be initiated at a starting dose of 0.125 mg/m2. Subsequent doses will increase until a maximum tolerated dose (MTD) is established.

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Časové okno: Baseline up to 30 days after last dose of study drug
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event.
Baseline up to 30 days after last dose of study drug
Number of Participants Reporting at Least 1 TEAE Related to Laboratory Assessments
Časové okno: Baseline and Days 1, 8, and 15 of each treatment cycle (up to Cycle 45)
The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Hematology, clinical chemistry and urinalysis were performed. TEAEs related to laboratory assessment observed at any time-points were reported under 3 system organ classes: blood and lymphatic system disorders, metabolism and nutrition disorders, and investigations.
Baseline and Days 1, 8, and 15 of each treatment cycle (up to Cycle 45)
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Časové okno: Baseline and Days 1, 8, 15 of each treatment cycle up to 45 treatment cycles
Vital signs included body temperature, weight, systolic and diastolic blood pressure and heart rate.
Baseline and Days 1, 8, 15 of each treatment cycle up to 45 treatment cycles
Maximum Tolerated Dose (MTD)
Časové okno: Treatment Cycle 1
The MTD was defined as the highest dose of ixazomib that generated dose limiting toxicity (DLT) during Cycle 1 in 0 of 3 or 1 of 6 participants. DLT defined as any of the following considered possibly related to therapy by investigator: Grade 4 neutropenia (absolute neutrophil count [ANC] <500 cell per cubic millimeter [cells/mm^3]) for >7 days; Grade 3 neutropenia with fever or infection; Grade 4 thrombocytopenia for >7 days; platelet count <25,000 cells/mm^3; Grade 3 thrombocytopenia with clinically significant bleeding; platelet count <10,000/mm^3; Grade 2 peripheral neuropathy with pain or Grade 3 peripheral neuropathy; >=Grade 3 nausea/emesis, diarrhea controlled by maximal supportive therapy; Grade 3 QTc prolongation>500 millisecond (msec);any >=Grade 3 nonhematologic toxicity except arthralgia/myalgia; <1 week fatigue; delay in the initiation of the subsequent therapy cycle by >=7 days ; other Grade 2 ixazomib-related nonhematologic toxicities requiring therapy discontinuation.
Treatment Cycle 1
Recommended Phase 2 Dose (RP2D)
Časové okno: Baseline up to Treatment Cycle 45
The RP2D of Ixazomib was determined in Part 1 (dose escalation) on the basis of the totality of safety, tolerability, pharmacokinetics (PK), pharmacodynamic and preliminary efficacy data observed in Cycles 1 and 2 and beyond.
Baseline up to Treatment Cycle 45

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
C0: Initial Plasma Concentration After Bolus Intravenous Administration
Časové okno: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 336 hours postdose)
C0 is the plasma drug concentration at time zero following bolus intravenous injection, obtained from the plasma concentration-time curve.
Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 336 hours postdose)
AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for Ixazomib
Časové okno: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
AUC(0-168) is a measure of the area under the plasma concentration time-curve from time 0 to 168 hours postdose
Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
Terminal Phase Elimination Half-life (T1/2) for Ixazomib
Časové okno: Cycle 1 Day 15: Predose and at multiple time points (up to 336 hours postdose)
Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.
Cycle 1 Day 15: Predose and at multiple time points (up to 336 hours postdose)
Rac: Accumulation Ratio for Ixazomib
Časové okno: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
Rac was estimated as the ratio of AUC (0-168) on Day 15 and AUC (0-168) on Day 1. AUC (0-168) is the area under the plasma concentration-time curve from time 0 to 168 hours postdose.
Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
Ae (0-4): Amount of Drug Excreted in Urine From 0 to 4 Hours Postdose
Časové okno: Cycle 1, Days 1 and 15: 0 to 4 hours postdose
Ae (0-4) is the total amount of drug excreted in the urine from 0 to 4 hours postdose.
Cycle 1, Days 1 and 15: 0 to 4 hours postdose
Fe (0-4): Fraction of Dose Excreted Unchanged in Urine From 0 to 4 Hours Postdose
Časové okno: Cycle 1, Days 1 and 15: 0 to 4 hours postdose
Fe (0-4) is the fraction of the dose excreted unchanged in the urine from 0 to 4 hours postdose, calculated as percentage of the exact dose administered.
Cycle 1, Days 1 and 15: 0 to 4 hours postdose
CLr: Renal Clearance
Časové okno: Cycle 1, Days 1 and 15: 0 to 4 hours postdose
CLr is the volume of plasma from which the drug is completely removed by the kidney in a given amount of time, calculated as the amount of drug excreted in the urine divided by the area under the plasma concentration-time curve, expressed in liter per hour (L/hr).
Cycle 1, Days 1 and 15: 0 to 4 hours postdose
Emax: Maximum Observed Effect for Ixazomib
Časové okno: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
Emax is the maximum inhibition of 20S proteasome activity in whole blood.
Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
TEmax: Time to Maximum Observed Effect (Emax) for Ixazomib
Časové okno: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
TEmax: Time to reach the maximum observed effect (Emax), equal to time (hours) to Emax.
Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
Overall Best Response
Časové okno: Baseline up to Cycle 45
Overall best response is the best response observed for a participant during the study based on International Working Group (IWG) Response Criteria for malignant lymphoma. Complete response (CR) as per IWG is complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. Partial response (PR) is a minimum of 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses and no increase in the size of other nodes. Stable disease (SD) is when a participant fails to attain the criteria needed for a CR or PR, but does not fulfill those for PD. PD is any new lesion or increase by >50% of previously involved sites from nadir.
Baseline up to Cycle 45

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Millennium Pharmaceuticals, Inc.

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia

1. srpna 2009

Primární dokončení (Aktuální)

1. října 2014

Dokončení studie (Aktuální)

1. října 2014

Termíny zápisu do studia

První předloženo

4. května 2009

První předloženo, které splnilo kritéria kontroly kvality

5. května 2009

První zveřejněno (Odhad)

6. května 2009

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Odhad)

11. listopadu 2015

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

12. října 2015

Naposledy ověřeno

1. října 2015

Více informací

Termíny související s touto studií

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • C16002
  • U1111-1166-8981 (Identifikátor registru: WHO (UTN))

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