Combination Chemotherapy With or Without Bortezomib in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma
A Parallel Randomised Phase II Trial of CHOP Chemotherapy With or Without Bortezomib in Relapsed Mantle Cell Lymphoma
RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisolone, work in different ways to stop the growth of cancer cells, either by killing the cells or stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with bortezomib may kill more cancer cells. It is not yet known whether combination chemotherapy is more effective with or without bortezomib in treating mantle cell lymphoma.
PURPOSE: This randomized phase II trial is studying combination chemotherapy and bortezomib to see how well they work compared with combination chemotherapy alone in treating patients with relapsed or refractory mantle cell lymphoma. Combination chemotherapy alone (Arm I) has been discontinued April 2012 on recommendation of the DMC.
Aperçu de l'étude
Statut
Les conditions
Description détaillée
OBJECTIVES:
Primary
- To evaluate the rates of overall response (complete response [CR], CR unconfirmed [CRu], and partial response).
Secondary
- To evaluate the rates of CR and CRu.
- To determine the median time to progression.
- To determine the median overall survival.
- To evaluate the toxicity and tolerability.
- To compare the responses to these treatment regimens with those from first line therapy.
- To compare the quality of life.
OUTLINE: This is a randomized, open-label, parallel group, multicenter study. Patients are randomized to 1 of 2 treatment arms.
- Arm I (CHOP): Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV, and vincristine IV on day 1 and oral prednisolone on days 1-5. Arm I has been discontinued April 2012 on recommendation of the DMC.
- Arm II (CHOP with bortezomib): Patients receive bortezomib IV over 3-5 seconds on days 1 and 8; doxorubicin hydrochloride IV, cyclophosphamide IV, and vincristine IV on day 1; and oral prednisolone on days 1-5.
In both arms, treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Patients complete quality of life questionnaires at baseline, prior to each treatment course, and then at 30 days after completion of treatment.
After completion of study treatment, patients are followed at 30 days and then every 12 weeks thereafter.
Type d'étude
Inscription (Réel)
Phase
- Phase 2
Contacts et emplacements
Lieux d'étude
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England
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Basingstoke, England, Royaume-Uni, RG24 9NA
- Basingstoke and North Hampshire NHS Foundation Trust
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Birmingham, England, Royaume-Uni, B9 5SS
- Birmingham Heartlands Hospital
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Birmingham, England, Royaume-Uni, B75 7RR
- Good Hope Hospital
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Blackpool, England, Royaume-Uni, FY3 8NR
- Blackpool Victoria Hospital
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Cambridge, England, Royaume-Uni, CB2 2QQ
- Addenbrooke's Hospital
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Dartford, England, Royaume-Uni, DA2 8DA
- Darent Valley Hospital
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Harrogate, England, Royaume-Uni, HG2 7SX
- Harrogate District Hospital
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Leeds, England, Royaume-Uni, LS1 3EX
- Leeds General Infirmary
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Liverpool, England, Royaume-Uni, L7 8XP
- Royal Liverpool University Hospital
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London, England, Royaume-Uni, SE1 9RT
- Guy's Hospital
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Maidstone, England, Royaume-Uni, ME16 9QQ
- Mid Kent Oncology Centre at Maidstone Hospital
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Newcastle-Upon-Tyne, England, Royaume-Uni, NE1 4LP
- Royal Victoria Infirmary
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Norfolk, England, Royaume-Uni, NR31 6LA
- James Paget Hospital
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Norwich, England, Royaume-Uni, NR4 7UY
- Norfolk and Norwich University Hospital
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Plymouth, England, Royaume-Uni, PL6 8DH
- Derriford Hospital
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Prescot Merseyside, England, Royaume-Uni, L35 5DR
- Whiston Hospital
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Southampton, England, Royaume-Uni, SO16 6YD
- Southampton General Hospital
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Sunderland, England, Royaume-Uni, SR4 7TP
- Sunderland Royal Hospital
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Taunton, England, Royaume-Uni, TA1 5DA
- Musgrove Park Hospital
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Torquay, England, Royaume-Uni, TQ2 7AA
- Torbay Hospital
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Truro, Cornwall, England, Royaume-Uni, TR1 3LJ
- Royal Cornwall Hospital
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Scotland
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Aberdeen, Scotland, Royaume-Uni, AB25 2ZN
- Aberdeen Royal Infirmary
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Inverness, Scotland, Royaume-Uni, 1V2 3UJ
- Raigmore Hospital
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Wales
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Bangor, Wales, Royaume-Uni, LL57 2PW
- Ysbyty Gwynedd
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Llanelli, Wales, Royaume-Uni, SA14 8QF
- Prince Philip Hospital
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
DISEASE CHARACTERISTICS:
Diagnosis of mantle cell lymphoma (MCL)
- Expression of cyclin D1 or evidence of t(11;14) translocation by cytogenetics, FISH, or polymerase chain reaction
- Refractory to or relapsed or progressed after first line antineoplastic therapy
- Measurable disease
PATIENT CHARACTERISTICS:
Inclusion criteria:
- Karnofsky performance status (PS) 50-100% OR ECOG PS 0-2
- ANC ≥ 1,000/mm³ (not related to lymphoma)
- Platelet count ≥ 30,000/mm³
- AST and ALT ≤ 3 times upper limit of normal (ULN)
- Total bilirubin ≤ 2 times ULN
- Creatinine clearance ≥ 20 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
Exclusion criteria:
- Known serological positivity for HBV, HCV, or HIV
- History of allergic reaction attributable to compounds containing boron or mannitol
- Diagnosed or treated for a malignancy other than MCL within the past 5 years except for completely resected basal cell or squamous cell carcinoma of the skin or any in situ malignancy
- Active systemic infection requiring treatment
- Serious medical or psychiatric illness that would preclude study participation
PRIOR CONCURRENT THERAPY:
Inclusion criteria:
- Toxic effects of prior therapy or surgery must be resolved to ≤ grade 2
- Prior splenectomy or localized radiotherapy allowed
Any prior chemotherapy regimen allowed
- Chemotherapy may have been given in combination with rituximab
- Concurrent enrollment in a nontreatment study allowed, provided it does not interfere with participation in this study
Exclusion criteria:
- Prior bortezomib
- Antineoplastic therapy within the past 3 weeks
- Nitrosoureas within the past 6 weeks
- Rituximab, alemtuzumab (Campath®), or other unconjugated therapeutic antibody within the past 4 weeks
- Radiotherapy within the past 3 weeks
- Major surgery within the past 2 weeks
- Concurrent investigational agents
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: Bortezomib plus CHOP
Patients receive bortezomib IV over 3-5 seconds on days 1 and 8; doxorubicin hydrochloride IV, cyclophosphamide IV, and vincristine IV on day 1; and oral prednisolone on days 1-5. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients complete quality of life questionnaires at baseline, prior to each treatment course, and then at 30 days after completion of treatment. After completion of study treatment, patients are followed at 30 days and then every 12 weeks thereafter. |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Disease progression
Délai: 30 days and every 12 weeks
|
The follow-up visits will be at 30 days after last dose of study drug and after that every 12 weeks until: Progressive disease, initiation of further anti-neoplastic therapy, patient decision to withdraw from the study, patient death.
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30 days and every 12 weeks
|
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Unacceptable toxicity or tolerability as assessed by NCI CTCAE v3.0
Délai: continual after first drug dose
|
The follow-up visits will be at 30 days after last dose of study drug and after that every 12 weeks until: Progressive disease, initiation of further anti-neoplastic therapy, patient decision to withdraw from the study, patient death.
|
continual after first drug dose
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chaise d'étude: Simon Rule, MD, Derriford Hospital
Publications et liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Maladies du système immunitaire
- Tumeurs par type histologique
- Tumeurs
- Troubles lymphoprolifératifs
- Maladies lymphatiques
- Troubles immunoprolifératifs
- Lymphome non hodgkinien
- Lymphome
- Lymphome à cellules du manteau
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Inhibiteurs d'enzymes
- Agents anti-inflammatoires
- Agents antirhumatismaux
- Agents antinéoplasiques
- Agents immunosuppresseurs
- Facteurs immunologiques
- Modulateurs de tubuline
- Agents antimitotiques
- Modulateurs de mitose
- Glucocorticoïdes
- Les hormones
- Hormones, substituts hormonaux et antagonistes hormonaux
- Agents antinéoplasiques, hormonaux
- Agents antinéoplasiques, alkylants
- Agents d'alkylation
- Agonistes myéloablatifs
- Agents antinéoplasiques phytogéniques
- Inhibiteurs de la topoisomérase II
- Inhibiteurs de la topoisomérase
- Antibiotiques, Antinéoplasiques
- Prednisolone
- Cyclophosphamide
- Bortézomib
- Doxorubicine
- Doxorubicine liposomale
- Vincristine
Autres numéros d'identification d'étude
- CDR0000559820
- NCRN-Ply-26s
- EU-20747
- ISRCTN200600609024
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