Busulfan, Melphalan, Escalating Carfilzomib Conditioning Auto Stem Cell Transplantation for Multiple Myeloma (MM) (BuMelCarAuto)
23 avril 2021 mis à jour par: 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.
Aperçu de l'étude
Statut
Recrutement
Les conditions
Intervention / Traitement
Description détaillée
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.
Type d'étude
Interventionnel
Inscription (Anticipé)
36
Phase
- Phase 2
- La phase 1
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Coordonnées de l'étude
- Nom: Patrick Stiff, MD
- Numéro de téléphone: 708-327-3148
- E-mail: mailto:pstiff@lumc.edu
Sauvegarde des contacts de l'étude
- Nom: Mary Lee, RN
- Numéro de téléphone: 708-327-2241
- E-mail: mailto:mlee@luc.edu
Lieux d'étude
-
-
Illinois
-
Maywood, Illinois, États-Unis, 60153
- Recrutement
- Loyola University Medical Center
-
Contact:
- Mary Lee, RN
- Numéro de téléphone: 708-327-2241
- E-mail: mlee@luc.edu
-
Contact:
- Patrick Stiff, MD
- Numéro de téléphone: 708-327-3148
- E-mail: pstiff@lumc.edu
-
-
Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
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.
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Non randomisé
- Modèle interventionnel: Affectation séquentielle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: 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.
Autres noms:
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Autres noms:
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Autres noms:
|
|
Expérimental: 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.
Autres noms:
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Autres noms:
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Autres noms:
|
|
Expérimental: 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.
Autres noms:
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Autres noms:
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Autres noms:
|
|
Expérimental: 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.
Autres noms:
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Autres noms:
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Autres noms:
|
|
Expérimental: 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.
Autres noms:
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Autres noms:
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
36 participants evaluated for safety with treatment-related adverse events and grading by using CTCAE v4.0.
Délai: 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.
Délai: 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
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
36 participants evaluated for response to treatment by testing blood for multiple myeloma levels.
Délai: 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.
Délai: 3 years
|
Progression Free Survival
|
3 years
|
|
36 participants evaluated for overall survival by clinical visit or contact by phone.
Délai: 3 years
|
Overall Survival
|
3 years
|
|
36 participants evaluated for absolute neutrophil count by testing white blood cells levels.
Délai: 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.
Délai: 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.
Délai: 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.
Délai: 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.
Délai: 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.
Délai: 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.
Délai: 3 years
|
Progression Free Survival
|
3 years
|
Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Patrick Stiff, MD, Loyola University
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Réel)
22 mai 2019
Achèvement primaire (Anticipé)
1 novembre 2022
Achèvement de l'étude (Anticipé)
1 novembre 2023
Dates d'inscription aux études
Première soumission
17 octobre 2018
Première soumission répondant aux critères de contrôle qualité
3 janvier 2019
Première publication (Réel)
8 janvier 2019
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
26 avril 2021
Dernière mise à jour soumise répondant aux critères de contrôle qualité
23 avril 2021
Dernière vérification
1 avril 2021
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Maladies cardiovasculaires
- Maladies vasculaires
- Maladies du système immunitaire
- Tumeurs par type histologique
- Tumeurs
- Troubles lymphoprolifératifs
- Troubles immunoprolifératifs
- Maladies hématologiques
- Troubles hémorragiques
- Troubles hémostatiques
- Paraprotéinémies
- Troubles des protéines sanguines
- Myélome multiple
- Tumeurs, plasmocyte
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents antinéoplasiques
- Agents immunosuppresseurs
- Facteurs immunologiques
- Agents antinéoplasiques, alkylants
- Agents d'alkylation
- Agonistes myéloablatifs
- Melphalan
- Busulfan
Autres numéros d'identification d'étude
- 209274
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
NON
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Oui
Étudie un produit d'appareil réglementé par la FDA américaine
Non
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .