Busulfan, Melphalan, Escalating Carfilzomib Conditioning Auto Stem Cell Transplantation for Multiple Myeloma (MM) (BuMelCarAuto)
23. April 2021 aktualisiert von: 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.
Studienübersicht
Status
Rekrutierung
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
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.
Studientyp
Interventionell
Einschreibung (Voraussichtlich)
36
Phase
- Phase 2
- Phase 1
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienkontakt
- Name: Patrick Stiff, MD
- Telefonnummer: 708-327-3148
- E-Mail: mailto:pstiff@lumc.edu
Studieren Sie die Kontaktsicherung
- Name: Mary Lee, RN
- Telefonnummer: 708-327-2241
- E-Mail: mailto:mlee@luc.edu
Studienorte
-
-
Illinois
-
Maywood, Illinois, Vereinigte Staaten, 60153
- Rekrutierung
- Loyola University Medical Center
-
Kontakt:
- Mary Lee, RN
- Telefonnummer: 708-327-2241
- E-Mail: mlee@luc.edu
-
Kontakt:
- Patrick Stiff, MD
- Telefonnummer: 708-327-3148
- E-Mail: pstiff@lumc.edu
-
-
Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
18 Jahre und älter (Erwachsene, Älterer Erwachsener)
Akzeptiert gesunde Freiwillige
Nein
Studienberechtigte Geschlechter
Alle
Beschreibung
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.
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Nicht randomisiert
- Interventionsmodell: Sequenzielle Zuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
|
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.
|
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
Andere Namen:
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Andere Namen:
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Andere Namen:
|
|
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.
|
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
Andere Namen:
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Andere Namen:
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Andere Namen:
|
|
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.
|
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
Andere Namen:
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Andere Namen:
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Andere Namen:
|
|
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.
|
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
Andere Namen:
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Andere Namen:
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Andere Namen:
|
|
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.
|
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
Andere Namen:
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Andere Namen:
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Andere Namen:
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
36 participants evaluated for safety with treatment-related adverse events and grading by using CTCAE v4.0.
Zeitfenster: 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.
Zeitfenster: 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
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
36 participants evaluated for response to treatment by testing blood for multiple myeloma levels.
Zeitfenster: 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.
Zeitfenster: 3 years
|
Progression Free Survival
|
3 years
|
|
36 participants evaluated for overall survival by clinical visit or contact by phone.
Zeitfenster: 3 years
|
Overall Survival
|
3 years
|
|
36 participants evaluated for absolute neutrophil count by testing white blood cells levels.
Zeitfenster: 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.
Zeitfenster: 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.
Zeitfenster: 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.
Zeitfenster: 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.
Zeitfenster: 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.
Zeitfenster: 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.
Zeitfenster: 3 years
|
Progression Free Survival
|
3 years
|
Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Sponsor
Mitarbeiter
Ermittler
- Hauptermittler: Patrick Stiff, MD, Loyola University
Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn (Tatsächlich)
22. Mai 2019
Primärer Abschluss (Voraussichtlich)
1. November 2022
Studienabschluss (Voraussichtlich)
1. November 2023
Studienanmeldedaten
Zuerst eingereicht
17. Oktober 2018
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
3. Januar 2019
Zuerst gepostet (Tatsächlich)
8. Januar 2019
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
26. April 2021
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
23. April 2021
Zuletzt verifiziert
1. April 2021
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Herz-Kreislauf-Erkrankungen
- Gefäßerkrankungen
- Erkrankungen des Immunsystems
- Neubildungen nach histologischem Typ
- Neubildungen
- Lymphoproliferative Erkrankungen
- Immunproliferative Erkrankungen
- Hämatologische Erkrankungen
- Hämorrhagische Störungen
- Hämostasestörungen
- Paraproteinämien
- Bluteiweißstörungen
- Multiples Myelom
- Neubildungen, Plasmazelle
- Physiologische Wirkungen von Arzneimitteln
- Molekulare Mechanismen der pharmakologischen Wirkung
- Antineoplastische Mittel
- Immunsuppressive Mittel
- Immunologische Faktoren
- Antineoplastische Mittel, alkylierend
- Alkylierungsmittel
- Myeloablative Agonisten
- Melphalan
- Busulfan
Andere Studien-ID-Nummern
- 209274
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
NEIN
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Ja
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Nein
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