- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT00552396
An Open-label, Dose-escalation Safety and Tolerability Trial Assessing Anti-KIR (1-7F9) in Subjects With Multiple Myeloma
An Open-label, Dose-escalation Safety and Tolerability Trial Assessing Multiple Dose Administrations of Anti-KIR (1-7F9) Human Monoclonal Antibody in Subjects With Multiple Myeloma
Studieöversikt
Detaljerad beskrivning
Trial Design:
The trial is an open-label, dose-escalation trial to determine the safety and tolerability of Anti-KIR (1-7F9) in subjects with relapsed or refractory multiple myeloma (RRMM). A 3+3 design will be employed for the first dosing cycle at each dose level. The 7 planned dose levels are 0.0003 mg/kg, 0.003 mg/kg, 0.015 mg/kg, 0.075 mg/kg, 0.3 mg/kg, 1.0 mg/kg and 3.0 mg/kg. The subjects will receive up to a total of 4 administrations of Anti-KIR (1-7F9) with a dosing interval between each administration of 4 weeks. Safety, toxicity, PK (pharmacokinetic) and PD (pharmacodynamic) obtained in the first 4 weeks after dosing per group will be the basis for dose-escalation decisions. There will be follow-up visits every week the one month after the first administration and every two weeks following the second, third and fourth administrations. After the last administration there will be follow-up visits every month until KIR occupancy is no longer detected.
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 1
Kontakter och platser
Studieorter
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Indiana
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Indianapolis, Indiana, Förenta staterna, 46202
- Indiana University Cancer Center
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New York
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New York City, New York, Förenta staterna, 10029
- Mont Sinai Medical Center
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Ohio
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Columbus, Ohio, Förenta staterna, 43210
- Ohio State University Medical Center
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Texas
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San Antonio, Texas, Förenta staterna, 78229-4427
- Cancer Therapy Research Center at UTHSCSA
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Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
Inclusion Criteria:
- Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject.)
- Bone marrow plasmacytosis > 10% (as determined by bone marrow aspirate) or plasmacytoma
- Relapse or progression after at least one prior systemic treatment regimen for Multiple Myeloma (MM) as evidenced by ≥ 25% increase in the M-protein as compared to the best response from the previous treatment regimen.
3a. One prior therapy for multiple myeloma, Measurable disease, as defined by persistent presence of serum and/or urine monoclonal protein or abnormal serum free light chain ratio following the prior treatment.
a. Only for the last seven patients enrolled into the cohort 7 or Maximal Tolerated Dose (MTD).
4. Full recovery from acute toxicities of prior anti-MM therapies. 5. Peripheral blood (Natural Killer) NK cells (Absolute CD16, 56)≥ 0.05 x 109/L (50/mm3) 6. Detectable binding of Anti-KIR (1-7F9) to subject NK cells 7. Age ≥ 18 years 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2 9. Clinical laboratory values at screening:
- serum creatinine < grade 2 toxicity i.e. 1.5x upper limit of institutional normal value
- total bilirubin < 1.5x upper limit of institutional normal value
- Aspartate aminotransferase (AST) < or = 3x upper limit of institutional normal value
- Absolute Neutrophil Count (ANC) >1.2 x109/L
- Platelets >70x109/L
Exclusion Criteria:
- Known or suspected allergy to trial product or related products
- Previous participation in this trial (dosed)
- Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (appropriate methods include abstinence and the following methods: diaphragm, condom (by the partner), intrauterine device, sponge, spermicide or oral contraceptives)
- Male subjects who are sexually active and have not been surgically sterilized must be informed that they must either use a condom during intercourse, ensure that their partners practices contraception, or they must refrain from sexual intercourse during the study and until 1 month after completion of the trial.
- Use of an investigational agent within 30 days of the first dose of study drug (or five half-lives of any antibody).
- Current treatment with any other anti-MM therapy excluding prophylactic bisphosphonates.
- Radiotherapy against bone lesions within 4 weeks or visceral lesions within 8 weeks of Screening.
- Thalidomide or bortezomib treatment within 14 days of Screening.
- Cytotoxic chemotherapy (excluding thalidomide or bortezomib) or corticosteroid treatment within 28 days of Screening.
- Subjects with non-secretory multiple myeloma
- Subjects on dialysis
- Use of myeloid growth factor within 28 days of screening
- G-CSF treatment within 28 days of screening
- Active autoimmune disease
- Active infectious disease (e.g. HIV, chronic hepatitis, etc.) as judged by the investigator.
- New York Heart Association (NYHA) class III-IV heart failure
- Severe neurological / psychiatric disorder as judged by the investigator
- Clinical evidence of an active second malignancy, with the exception of basal cell carcinoma or in situ carcinoma of cervix.
- Subjects with a history of allogenic transplantation.
- Subject who have undergone autologous transplantation within the last 3 months.
- Mental incapacity or inadequate understanding of English.
- Any serious medical condition that in the opinion of the investigator, disqualifies the subject for inclusion in the trial.
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: N/A
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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Maximum Tolerated Dose (MTD) of IPH2101 as Determined by Number of Participants With Dose-Limiting Toxicities (DLTs) Related to IPH2101 Treatment
Tidsram: From start of the treatment to end of study
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The maximum tolerated dose (MTD) is the highest dose level below the maximum administered dose (MAD) where none or 1 out of 6 subjects have a DLT.
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From start of the treatment to end of study
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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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Maximum Plasma Concentration (Cmax) of IPH2101 After Cycle 1 Administration
Tidsram: Anti-KIR (1-7F9) concentrations were measured prior to infusion at 0.167, 1, 3, 6, 12 and 24 hours and then on Days 7, 14 and 21 after the start of the first dose administration
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Cmax was obtained from the plasma concentration versus time data after IV administration of IPH2101.
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Anti-KIR (1-7F9) concentrations were measured prior to infusion at 0.167, 1, 3, 6, 12 and 24 hours and then on Days 7, 14 and 21 after the start of the first dose administration
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Area Under the Plasma-concentration-time Curve [AUC (INF)] of IPH2101 After Cycle 1 Administration
Tidsram: Anti-KIR (1-7F9) concentrations were measured prior to infusion at 0.167, 1, 3, 6, 12 and 24 hours and then on Days 7, 14 and 21 after the start of the first dose administration
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AUC(INF), area under the plasma concentration-time curve from zero to the last time of the last quantifiable concentration within the dosing interval was calculated for Cycle 1.
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Anti-KIR (1-7F9) concentrations were measured prior to infusion at 0.167, 1, 3, 6, 12 and 24 hours and then on Days 7, 14 and 21 after the start of the first dose administration
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Number of Evaluable Patients With Stable Disease. "Evaluable" is Defined as 2 Consecutive M Protein Assessments
Tidsram: From start of the treatment to end of study or disease progression
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Disease Response Assessment by Principal Investigator and Sponsor(Efficacy Population).Stable Disease was defined as not meeting criteria for complete response, very good partial response, partial response, or progressive disease
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From start of the treatment to end of study or disease progression
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Samarbetspartners och utredare
Sponsor
Utredare
- Huvudutredare: Sherif Farag, MD, PhD, Indiana University
- Huvudutredare: Don Benson, Jr., MD, PhD, Division of Haematology/Oncology - Ohio State University
- Huvudutredare: Swaminathan Padmanabhan, MD, CTRC Institute for Drug Development - University of Texas at San Antonio
- Huvudutredare: Sundar Jagannath, MD, Mount Sinai Hospital, New York
Publikationer och användbara länkar
Studieavstämningsdatum
Studera stora datum
Studiestart
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Uppskatta)
Uppdateringar av studier
Senaste uppdatering publicerad (Uppskatta)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
- Hjärt-kärlsjukdomar
- Kärlsjukdomar
- Immunsystemets sjukdomar
- Neoplasmer efter histologisk typ
- Neoplasmer
- Lymfoproliferativa störningar
- Immunproliferativa störningar
- Hematologiska sjukdomar
- Hemorragiska störningar
- Hemostatiska störningar
- Paraproteinemier
- Blodproteinstörningar
- Multipelt myelom
- Neoplasmer, Plasmacell
Andra studie-ID-nummer
- IPH2101-103
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