Esta página foi traduzida automaticamente e a precisão da tradução não é garantida. Por favor, consulte o versão em inglês para um texto fonte.

Busulfan, Melphalan, Escalating Carfilzomib Conditioning Auto Stem Cell Transplantation for Multiple Myeloma (MM) (BuMelCarAuto)

23 de abril de 2021 atualizado por: Patrick Stiff, Loyola University

Phase I/II Study Utilizing High Dose Busulfan and Melphalan With Escalating Carfilzomib as Conditioning in Autologous Peripheral Blood Stem Cell Transplantation for Patients With Multiple Myeloma

In this protocol, the investigators hypothesize that the combination of intravenous busulfan and melphalan with carfilzomib will be an effective preparative regimen with acceptable toxicity for participants with multiple myeloma who are candidates for autologous stem cell transplantation. To test this hypothesis, the investigators designed a phase I/II trial combining IV busulfan 130 mg/m2 plus melphalan 140 mg combined with escalating doses of carfilzomib ranging from 20 mg/m2 to 45 mg/m2. These results will be compared with the center's historical controls of participants treated with melphalan, busulfan and bortezomib.

Visão geral do estudo

Status

Recrutamento

Condições

Intervenção / Tratamento

Descrição detalhada

Participants enrolled in this study protocol will receive daily intravenous (IV) infusions of carfilzomib for a total of 4 days (Day-9, -8 and Days -2, -1). The first two daily infusions will be given at a fixed dose of 20 mg/m2 and the final two doses will be escalated from the standard dose of 27 mg/m2 to 56 mg/m2 in a Phase I design, based on toxicity. The busulfan will be administered for 2 days over 3 hours from D-7, -6, at 130 mg/m2 . This dose was found to be safe and equivalent to the standard daily dose of 3.2 mg/kg. The 3rd and 4th daily doses of IV Busulfan will be adjusted in order to yield a systemic plasma drug exposure represented by a daily area under the plasma concentration versus time curve (AUC) of approximately 5,000 millimoles-minute per dose (mM-min). These targeted plasma concentration of IV busulfan will be based on pharmacokinetics studies performed during the first day of IV busulfan. Melphalan will be given at a dose of 140 mg/m2 on Day -3. Each cohort will start with a goal of accruing three patients to determine the dose limiting toxicity.

Tipo de estudo

Intervencional

Inscrição (Antecipado)

36

Estágio

  • Fase 2
  • Fase 1

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Estude backup de contato

Locais de estudo

  • Estados Unidos
    • Illinois
      • Maywood, Illinois, Estados Unidos, 60153
        • Recrutamento
        • Loyola University Medical Center
        • Contato:
          • Mary Lee, RN
          • Número de telefone: 708-327-2241
          • E-mail: mlee@luc.edu
        • Contato:
          • Patrick Stiff, MD
          • Número de telefone: 708-327-3148
          • E-mail: pstiff@lumc.edu

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos e mais velhos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

Inclusion Criteria:

  • Participants must be greater than or equal to 18 years of age.
  • Participants must have been diagnosed with multiple myeloma in a first or subsequent remission and have undergone a successful pre-transplant work up and are otherwise eligible for an autotransplant with a busulfan/melphalan preparative regimen at Loyola University Medical Center.
  • Participants may receive this preparative regimen if in first or subsequent remission. Participants may enter if they have received a prior autologous stem cell transplant and this therapy produced a remission that lasted greater than 18 months before progression of disease. Participants who have undergone prior allogeneic transplantation are excluded.
  • All participants must have responsive disease as defined by a Partial Response or greater to most recent conventional regimen.
  • Participants receiving prior carfilzomib will be eligible for inclusion provided they demonstrated responsive disease to this agent and either had a remission that lasted greater than 6 months after its discontinuance, or if in remission after a carfilzomib containing regimen administered to qualify for transplant.
  • Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) less than or equal to 2.
  • Acceptable heart function test.

Exclusion Criteria:

  • Participants must not have below normal kidney function.
  • Participants must not have below normal liver function.
  • Participants must not have active bacterial, fungal, or viral infection.
  • Participants must not have severe lung function.
  • Participants must not have Grade 2 or greater peripheral neuropathy.
  • Participants must not have uncontrolled hypertension.

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Não randomizado
  • Modelo Intervencional: Atribuição sequencial
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: Carfilzomib IV at dose: 20 mg/m2
The participants will receive Carfilzomib IV at dose: 20 mg/m2 on days -9 and -8 over 30 minutes. The participant will receive Busulfan IV over 3 hours every 24 hours for a total of 4 doses from Day -6 to Day -3 and Melphalan IV over 15-30 minutes for one dose on day -3.The participants will receive stem cell infusion on Day 0 and Granulocyte-Colony stimulating factor (G-CSF) given daily until engraftment occurs.
Medicamento: Carfilzomib
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
Outros nomes:
  • Kyprolis
Medicamento: Busulfan IV
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Outros nomes:
  • Bussulfex
Medicamento: Melphalan IV
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Outros nomes:
  • Alkeran
Experimental: Carfilzomib IV at dose: 27 mg/m2
The participants will receive Carfilzomib IV at dose: 27 mg/m2 on days -9 and -8 over 30 minutes. The participant will receive Busulfan IV over 3 hours every 24 hours for a total of 4 doses from Day -6 to Day -3 and Melphalan IV over 15-30 minutes for one dose on day -3.The participants will receive stem cell infusion on Day 0 and G-CSF given daily until engraftment occurs.
Medicamento: Carfilzomib
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
Outros nomes:
  • Kyprolis
Medicamento: Busulfan IV
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Outros nomes:
  • Bussulfex
Medicamento: Melphalan IV
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Outros nomes:
  • Alkeran
Experimental: Carfilzomib IV at dose: 36 mg/m2
The participants will receive Carfilzomib IV at dose: 36 mg/m2 on days -9 and -8 over 30 minutes. The participant will receive Busulfan IV over 3 hours every 24 hours for a total of 4 doses from Day -6 to Day -3 and Melphalan IV over 15-30 minutes for one dose on day -3.The participants will receive stem cell infusion on Day 0 and G-CSF given daily until engraftment occurs.
Medicamento: Carfilzomib
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
Outros nomes:
  • Kyprolis
Medicamento: Busulfan IV
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Outros nomes:
  • Bussulfex
Medicamento: Melphalan IV
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Outros nomes:
  • Alkeran
Experimental: Carfilzomib IV at dose: 45 mg/m2
The participants will receive Carfilzomib IV at dose: 45 mg/m2 on days -9 and -8 over 30 minutes. The participant will receive Busulfan IV over 3 hours every 24 hours for a total of 4 doses from Day -6 to Day -3 and Melphalan IV over 15-30 minutes for one dose on day -3.The participants will receive stem cell infusion on Day 0 and G-CSF given daily until engraftment occurs.
Medicamento: Carfilzomib
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
Outros nomes:
  • Kyprolis
Medicamento: Busulfan IV
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Outros nomes:
  • Bussulfex
Medicamento: Melphalan IV
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Outros nomes:
  • Alkeran
Experimental: Carfilzomib IV at dose: 56 mg/m2
The participants will receive Carfilzomib IV at dose: 56 mg/m2 on days -9 and -8 over 30 minutes. The participant will receive Busulfan IV over 3 hours every 24 hours for a total of 4 doses from Day -6 to Day -3 and Melphalan IV over 15-30 minutes for one dose on day -3.The participants will receive stem cell infusion on Day 0 and G-CSF given daily until engraftment occurs.
Medicamento: Carfilzomib
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
Outros nomes:
  • Kyprolis
Medicamento: Busulfan IV
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Outros nomes:
  • Bussulfex
Medicamento: Melphalan IV
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Outros nomes:
  • Alkeran

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
36 participants evaluated for safety with treatment-related adverse events and grading by using CTCAE v4.0.
Prazo: 3 years
To determine the maximal tolerated dose of carfilzomib when added to busulfan and melphalan as a preparative regimen for high dose therapy with autologous hematopoietic transplantation for patients with multiply myeloma.
3 years
36 participants evaluated for tolerability with treatment-related adverse events and grading by using CTCAE v4.0.
Prazo: 3 years
To determine the maximal tolerated dose of carfilzomib when added to busulfan and melphalan as a preparative regimen for high dose therapy with autologous hematopoietic transplantation for patients with multiply myeloma.
3 years

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
36 participants evaluated for response to treatment by testing blood for multiple myeloma levels.
Prazo: 100 days
To evaluate complete, very good partial, partial and stable disease response rate for both clinical and biologic endpoints.
100 days
36 participants evaluated for progression by testing blood for multiple myeloma levels.
Prazo: 3 years
Progression Free Survival
3 years
36 participants evaluated for overall survival by clinical visit or contact by phone.
Prazo: 3 years
Overall Survival
3 years
36 participants evaluated for absolute neutrophil count by testing white blood cells levels.
Prazo: 100 days
Days to neutrophil engraftment: Absolute neutrophil count > 500/microliter
100 days
36 participants evaluated for platelet engraftment by testing platelet count in blood cells.
Prazo: 100 days
Days to platelet engraftment: platelet count > 20,000/microliter untransfused
100 days
36 participants evaluated by oral exam to assess mucositis events and grading levels by using CTCAE v4.0.
Prazo: 100 days
Mucositis: CTCAE v 4.0 grade and severity
100 days
36 participants evaluated by the liver to assess Veno-occlusive disease and grading levels by using CTCAE v4.0.
Prazo: 100 days
Veno-occlusive disease
100 days
36 participants evaluated by a physical exam to assess peripheral neuropathy and grading by using CTCAE v4.0.
Prazo: 3 years
Peripheral neuropathy greater than or equal to CTCAE V 4.0 Grade 3
3 years
36 participants evaluated for response to treatment by testing urine for multiple myeloma levels.
Prazo: 100 days
To evaluate complete, very good partial, partial no stable disease response rate for both clinical and biologic endpoints
100 days
36 participants evaluated for progression by testing urine for multiple myeloma levels.
Prazo: 3 years
Progression Free Survival
3 years

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Loyola University

Colaboradores

Amgen

Investigadores

  • Investigador principal: Patrick Stiff, MD, Loyola University

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

22 de maio de 2019

Conclusão Primária (Antecipado)

1 de novembro de 2022

Conclusão do estudo (Antecipado)

1 de novembro de 2023

Datas de inscrição no estudo

Enviado pela primeira vez

17 de outubro de 2018

Enviado pela primeira vez que atendeu aos critérios de CQ

3 de janeiro de 2019

Primeira postagem (Real)

8 de janeiro de 2019

Atualizações de registro de estudo

Última Atualização Postada (Real)

26 de abril de 2021

Última atualização enviada que atendeu aos critérios de controle de qualidade

23 de abril de 2021

Última verificação

1 de abril de 2021

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • 209274

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

NÃO

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Sim

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

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 .

Se inscrever