- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico 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
Visão geral do estudo
Descrição detalhada
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.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 1
Contactos e Locais
Locais de estudo
-
-
Indiana
-
Indianapolis, Indiana, Estados Unidos, 46202
- Indiana University Cancer Center
-
-
New York
-
New York City, New York, Estados Unidos, 10029
- Mont Sinai Medical Center
-
-
Ohio
-
Columbus, Ohio, Estados Unidos, 43210
- Ohio State University Medical Center
-
-
Texas
-
San Antonio, Texas, Estados Unidos, 78229-4427
- Cancer Therapy Research Center at UTHSCSA
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
---|---|---|
Maximum Tolerated Dose (MTD) of IPH2101 as Determined by Number of Participants With Dose-Limiting Toxicities (DLTs) Related to IPH2101 Treatment
Prazo: From start of the treatment to end of study
|
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.
|
From start of the treatment to end of study
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
---|---|---|
Maximum Plasma Concentration (Cmax) of IPH2101 After Cycle 1 Administration
Prazo: 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
|
Cmax was obtained from the plasma concentration versus time data after IV administration of IPH2101.
|
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
|
Area Under the Plasma-concentration-time Curve [AUC (INF)] of IPH2101 After Cycle 1 Administration
Prazo: 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
|
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.
|
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
|
Number of Evaluable Patients With Stable Disease. "Evaluable" is Defined as 2 Consecutive M Protein Assessments
Prazo: From start of the treatment to end of study or disease progression
|
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
|
From start of the treatment to end of study or disease progression
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Sherif Farag, MD, PhD, Indiana University
- Investigador principal: Don Benson, Jr., MD, PhD, Division of Haematology/Oncology - Ohio State University
- Investigador principal: Swaminathan Padmanabhan, MD, CTRC Institute for Drug Development - University of Texas at San Antonio
- Investigador principal: Sundar Jagannath, MD, Mount Sinai Hospital, New York
Publicações e links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças cardiovasculares
- Doenças Vasculares
- Doenças do sistema imunológico
- Neoplasias por Tipo Histológico
- Neoplasias
- Distúrbios Linfoproliferativos
- Distúrbios imunoproliferativos
- Doenças Hematológicas
- Distúrbios hemorrágicos
- Distúrbios hemostáticos
- Paraproteinemias
- Distúrbios das Proteínas Sanguíneas
- Mieloma múltiplo
- Neoplasias de Células Plasmáticas
Outros números de identificação do estudo
- IPH2101-103
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .
Ensaios clínicos em Anti-KIR (1-7F9)
-
Innate PharmaConcluído
-
Innate PharmaConcluídoMieloma múltiplo latenteEstados Unidos
-
National Cancer Institute (NCI)RescindidoMieloma múltiplo | Mieloma múltiplo latente | MielomaEstados Unidos
-
Boston CollegeConcluídoBeber álcool | Violência na AdolescênciaEstados Unidos
-
Assistance Publique - Hôpitaux de ParisConcluídoDermatite | Síndrome de Sezary | Dermatite Esfoliativa | Fungicidas para MicoseFrança
-
Asociacion para el Estudio de las Enfermedades...Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon...ConcluídoSíndrome de liberação de citocinas | Doença viral | TLRsEspanha
-
Bristol-Myers SquibbConcluído
-
Bristol-Myers SquibbConcluídoCÂNCER, NÃOFrança, Canadá, Estados Unidos, Suíça, Espanha, Itália
-
OncoC4, Inc.Avance Clinical; OncoC4 AU Pty LtdRecrutamentoMelanoma | Carcinoma de Células Renais | Câncer cervical | Carcinoma hepatocelular | Câncer de intestino | Câncer colorretal | Câncer de esôfago | Câncer de Trompa de Falópio | Câncer de Pulmão de Células Não Pequenas | Cancro do ducto biliar | Câncer de bexiga | Câncer do endométrio | Carcinoma Espinocelular de... e outras condiçõesAustrália
-
Shanghai Junshi Bioscience Co., Ltd.Ativo, não recrutandoCarcinoma nasofaringeal | Adenocarcinoma Gástrico | Carcinoma Espinocelular de Cabeça e Pescoço | Carcinoma Espinocelular de EsôfagoChina