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

23 aprile 2021 aggiornato da: 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.

Panoramica dello studio

Stato

Reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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 di studio

Interventistico

Iscrizione (Anticipato)

36

Fase

  • Fase 2
  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Backup dei contatti dello studio

Luoghi di studio

  • Stati Uniti
    • Illinois
      • Maywood, Illinois, Stati Uniti, 60153
        • Reclutamento
        • Loyola University Medical Center
        • Contatto:
          • Mary Lee, RN
          • Numero di telefono: 708-327-2241
          • Email: mlee@luc.edu
        • Contatto:
          • Patrick Stiff, MD
          • Numero di telefono: 708-327-3148
          • Email: pstiff@lumc.edu

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Non randomizzato
  • Modello interventistico: Assegnazione sequenziale
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 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.
Droga: Carfilzomib
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
Altri nomi:
  • Kyprolis
Droga: Busulfan IV
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Altri nomi:
  • Busulfex
Droga: Melphalan IV
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Altri nomi:
  • Alkeran
Sperimentale: 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.
Droga: Carfilzomib
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
Altri nomi:
  • Kyprolis
Droga: Busulfan IV
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Altri nomi:
  • Busulfex
Droga: Melphalan IV
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Altri nomi:
  • Alkeran
Sperimentale: 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.
Droga: Carfilzomib
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
Altri nomi:
  • Kyprolis
Droga: Busulfan IV
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Altri nomi:
  • Busulfex
Droga: Melphalan IV
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Altri nomi:
  • Alkeran
Sperimentale: 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.
Droga: Carfilzomib
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
Altri nomi:
  • Kyprolis
Droga: Busulfan IV
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Altri nomi:
  • Busulfex
Droga: Melphalan IV
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Altri nomi:
  • Alkeran
Sperimentale: 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.
Droga: Carfilzomib
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
Altri nomi:
  • Kyprolis
Droga: Busulfan IV
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Altri nomi:
  • Busulfex
Droga: Melphalan IV
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Altri nomi:
  • Alkeran

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
36 participants evaluated for safety with treatment-related adverse events and grading by using CTCAE v4.0.
Lasso di tempo: 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.
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
36 participants evaluated for response to treatment by testing blood for multiple myeloma levels.
Lasso di tempo: 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.
Lasso di tempo: 3 years
Progression Free Survival
3 years
36 participants evaluated for overall survival by clinical visit or contact by phone.
Lasso di tempo: 3 years
Overall Survival
3 years
36 participants evaluated for absolute neutrophil count by testing white blood cells levels.
Lasso di tempo: 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.
Lasso di tempo: 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.
Lasso di tempo: 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.
Lasso di tempo: 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.
Lasso di tempo: 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.
Lasso di tempo: 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.
Lasso di tempo: 3 years
Progression Free Survival
3 years

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Loyola University

Collaboratori

Amgen

Investigatori

  • Investigatore principale: Patrick Stiff, MD, Loyola University

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

22 maggio 2019

Completamento primario (Anticipato)

1 novembre 2022

Completamento dello studio (Anticipato)

1 novembre 2023

Date di iscrizione allo studio

Primo inviato

17 ottobre 2018

Primo inviato che soddisfa i criteri di controllo qualità

3 gennaio 2019

Primo Inserito (Effettivo)

8 gennaio 2019

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

26 aprile 2021

Ultimo aggiornamento inviato che soddisfa i criteri QC

23 aprile 2021

Ultimo verificato

1 aprile 2021

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 209274

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Sì

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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