Busulfan, Melphalan, Escalating Carfilzomib Conditioning Auto Stem Cell Transplantation for Multiple Myeloma (MM) (BuMelCarAuto)
23 april 2021 bijgewerkt door: 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.
Studie Overzicht
Toestand
Werving
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
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.
Studietype
Ingrijpend
Inschrijving (Verwacht)
36
Fase
- Fase 2
- Fase 1
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studiecontact
- Naam: Patrick Stiff, MD
- Telefoonnummer: 708-327-3148
- E-mail: mailto:pstiff@lumc.edu
Studie Contact Back-up
- Naam: Mary Lee, RN
- Telefoonnummer: 708-327-2241
- E-mail: mailto:mlee@luc.edu
Studie Locaties
-
-
Illinois
-
Maywood, Illinois, Verenigde Staten, 60153
- Werving
- Loyola University Medical Center
-
Contact:
- Mary Lee, RN
- Telefoonnummer: 708-327-2241
- E-mail: mlee@luc.edu
-
Contact:
- Patrick Stiff, MD
- Telefoonnummer: 708-327-3148
- E-mail: pstiff@lumc.edu
-
-
Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
18 jaar en ouder (Volwassen, Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Beschrijving
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.
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Niet-gerandomiseerd
- Interventioneel model: Sequentiële toewijzing
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Experimenteel: 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:
|
|
Experimenteel: 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:
|
|
Experimenteel: 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:
|
|
Experimenteel: 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:
|
|
Experimenteel: 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:
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
36 participants evaluated for safety with treatment-related adverse events and grading by using CTCAE v4.0.
Tijdsspanne: 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.
Tijdsspanne: 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
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
36 participants evaluated for response to treatment by testing blood for multiple myeloma levels.
Tijdsspanne: 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.
Tijdsspanne: 3 years
|
Progression Free Survival
|
3 years
|
|
36 participants evaluated for overall survival by clinical visit or contact by phone.
Tijdsspanne: 3 years
|
Overall Survival
|
3 years
|
|
36 participants evaluated for absolute neutrophil count by testing white blood cells levels.
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: 3 years
|
Progression Free Survival
|
3 years
|
Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Sponsor
Medewerkers
Onderzoekers
- Hoofdonderzoeker: Patrick Stiff, MD, Loyola University
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start (Werkelijk)
22 mei 2019
Primaire voltooiing (Verwacht)
1 november 2022
Studie voltooiing (Verwacht)
1 november 2023
Studieregistratiedata
Eerst ingediend
17 oktober 2018
Eerst ingediend dat voldeed aan de QC-criteria
3 januari 2019
Eerst geplaatst (Werkelijk)
8 januari 2019
Updates van studierecords
Laatste update geplaatst (Werkelijk)
26 april 2021
Laatste update ingediend die voldeed aan QC-criteria
23 april 2021
Laatst geverifieerd
1 april 2021
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Hart-en vaatziekten
- Vaatziekten
- Ziekten van het immuunsysteem
- Neoplasmata per histologisch type
- Neoplasmata
- Lymfoproliferatieve aandoeningen
- Immunoproliferatieve aandoeningen
- Hematologische ziekten
- Hemorragische aandoeningen
- Hemostatische aandoeningen
- Paraproteïnemieën
- Bloed eiwit stoornissen
- Multipel myeloom
- Neoplasmata, plasmacel
- Fysiologische effecten van medicijnen
- Moleculaire mechanismen van farmacologische werking
- Antineoplastische middelen
- Immunosuppressieve middelen
- Immunologische factoren
- Antineoplastische middelen, alkylering
- Alkyleringsmiddelen
- Myeloablatieve agonisten
- Melfalan
- Busulfan
Andere studie-ID-nummers
- 209274
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
NEE
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Ja
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
Nee
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