Flavopiridol in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia or Lymphocytic Lymphoma
2 juin 2017 mis à jour par: National Cancer Institute (NCI)
A Dose-Escalation Study of Flavopiridol (NSC 649890) Administered as a 30 Minute Loading Dose Followed by a 4-Hour Infusion in Patients With Previously Treated B-Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
This phase I/II trial studies the side effects and best dose of flavopiridol in treating patients with previously treated chronic lymphocytic leukemia or lymphocytic lymphoma.
Drugs used in chemotherapy such as flavopiridol work in different ways to stop cancer cells from dividing so they stop growing or die.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Description détaillée
PRIMARY OBJECTIVES:
I. To determine the toxicity profile, dose-limiting toxicity, and maximum tolerated dose of flavopiridol administered as a 30 minute loading dose followed by a 4-hour infusion once weekly for 4 consecutive weeks every 6 weeks.
II. To determine the safety and feasibility of performing dose escalation to 80 mg/m2 (30 mg/m2 30-minute IV bolus followed by 50 mg/m2 4-hour IV infusion) beginning dose 2 in patients who do not experience severe tumor lysis requiring hemodialysis during dose 1.
III. To determine the pharmacokinetics and cellular pharmacodynamics of flavopiridol administered in this schedule.
SECONDARY OBJECTIVES:
I. To determine the complete response (CR) and overall response rate (CR + PR) of flavopiridol in patients with previously-treated CLL administered as a 30 minute loading dose followed by a 4 hour infusion once weekly for 4 consecutive weeks every 6 weeks.
OUTLINE: This is a dose-escalation study.
Patients receive a loading dose of flavopiridol IV over 30 minutes followed by a 4-hour infusion on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of unacceptable toxicity or disease progression.
Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. After the MTD is determined, 12 additional patients are accrued and treated as above at the recommended phase II dose.
After completion of study treatment, patients are followed at 2 months and then every 3 months for 2 years.
Type d'étude
Interventionnel
Inscription (Réel)
52
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.
Lieux d'étude
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Ohio
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Columbus, Ohio, États-Unis, 43210
- Ohio State University Medical Center
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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:
Diagnosis of B-cell chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma, including Waldenstrom's macroglobulinemia, as indicated by the following:
- Massive or progressive splenomegaly and/or lymphadenopathy
- Anemia (hemoglobin less than 11 g/dL) or thrombocytopenia (platelet count less than 100,000/mm^3)
- Weight loss of more than 10% within the past 6 months
- Grade 2 or 3 fatigue
- Fevers greater than 100.5º C or night sweats for more than 2 weeks with no evidence of infection
- Progressive lymphocytosis with an increase of more than 50% over a 2-month period or anticipated doubling time of less than 6 months
- Received at least 1 prior therapy for CLL
- Performance status - ECOG (Eastern Cooperative Oncology Group) 0-2
- See Disease Characteristics
- WBC (white blood count) less than 200,000/mm^3
- Bilirubin no greater than 1.5 times normal (unless due to Gilbert's disease or any of the conditions stated below)*
- AST (aspartate aminotransferase) no greater than 2 times normal*
- Creatinine no greater than 2.0 mg/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No other malignancy that would limit survival to less than 2 years
- No history of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis) unless inactive for more than 2 years
- No psychiatric condition that would preclude compliance with treatment or giving informed consent
- No other concurrent chemotherapy
- No concurrent chronic corticosteroids
- No concurrent hormonal therapy except steroids for new adrenal failure or hormonal agents for nondisease-related conditions (e.g., insulin for diabetes)
- No concurrent dexamethasone or other corticosteroid-based antiemetics
- No concurrent radiotherapy
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: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: Arm I
Patients receive a loading dose of flavopiridol IV over 30 minutes followed by a 4-hour infusion on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of unacceptable toxicity or disease progression.
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Étant donné IV
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Number of Patients With Dose Limiting Toxicities (DLTs)
Délai: up to 7 weeks
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DLTs were defined as non-hematologic toxicity of grade 3 or greater severity (excluding transient liver function abnormalities, transient electrolyte abnormalities that are not life threatening, fatigue, or diarrhea that resolve within 4 days), or in some case grade 2 toxicity (i.e.
irreversible renal, chronic pulmonary, neurologic, or cardiac toxicity).
Hematologic toxicity were evaluated by the modified NCI criteria and followed closely.
Dose limiting only if grade 4 thrombocytopenia or neutropenia persists for 7 days or greater.
Inability to continue with cycle 2 by 7 weeks for reasons other than progression of disease will also be considered a DLT.The National Cancer Institute Common Toxicity Criteria will be used to characterize toxicity.
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up to 7 weeks
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Recommended Dose Level of Flavopiridol
Délai: Up to 6 weeks
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Recommended dose determined by number of DLTs [non-hematologic toxicity grade 3 or greater (excluding not life-threatening transient liver function or transient electrolyte abnormalities, fatigue, or diarrhea resolving within 4 days), some grade 2 toxicity (i.e.
irreversible renal, chronic pulmonary, neurologic, or cardiac toxicity), hematologic toxicity of grade 4 thrombocytopenia/neutropenia persisting for 7 days or greater, or inability to continue cycle 2 by 7 weeks for reasons other than disease progression] and consideration of number of patients with severe tumor lysis requiring hemodialysis with dose 1.
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Up to 6 weeks
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Overall Response Rate (CR + PR) of Flavopiridol in Patients Evaluated Utilizing the Revised National Cancer Institute-sponsored Working Group Guidelines
Délai: Up to 2 years
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Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
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Up to 2 years
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Publications générales
- Lin TS, Ruppert AS, Johnson AJ, Fischer B, Heerema NA, Andritsos LA, Blum KA, Flynn JM, Jones JA, Hu W, Moran ME, Mitchell SM, Smith LL, Wagner AJ, Raymond CA, Schaaf LJ, Phelps MA, Villalona-Calero MA, Grever MR, Byrd JC. Phase II study of flavopiridol in relapsed chronic lymphocytic leukemia demonstrating high response rates in genetically high-risk disease. J Clin Oncol. 2009 Dec 10;27(35):6012-8. doi: 10.1200/JCO.2009.22.6944. Epub 2009 Oct 13.
- Pierceall WE, Warner SL, Lena RJ, Doykan C, Blake N, Elashoff M, Hoff DV, Bearss DJ, Cardone MH, Andritsos L, Byrd JC, Lanasa MC, Grever MR, Johnson AJ. Mitochondrial priming of chronic lymphocytic leukemia patients associates Bcl-xL dependence with alvocidib response. Leukemia. 2014 Nov;28(11):2251-4. doi: 10.1038/leu.2014.206. Epub 2014 Jul 3. No abstract available.
- Woyach JA, Lozanski G, Ruppert AS, Lozanski A, Blum KA, Jones JA, Flynn JM, Johnson AJ, Grever MR, Heerema NA, Byrd JC. Outcome of patients with relapsed or refractory chronic lymphocytic leukemia treated with flavopiridol: impact of genetic features. Leukemia. 2012 Jun;26(6):1442-4. doi: 10.1038/leu.2011.375. Epub 2012 Jan 13. No abstract available.
- Ni W, Ji J, Dai Z, Papp A, Johnson AJ, Ahn S, Farley KL, Lin TS, Dalton JT, Li X, Jarjoura D, Byrd JC, Sadee W, Grever MR, Phelps MA. Flavopiridol pharmacogenetics: clinical and functional evidence for the role of SLCO1B1/OATP1B1 in flavopiridol disposition. PLoS One. 2010 Nov 1;5(11):e13792. doi: 10.1371/journal.pone.0013792.
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)
1 avril 2003
Achèvement primaire (Réel)
1 février 2009
Achèvement de l'étude (Réel)
1 février 2009
Dates d'inscription aux études
Première soumission
7 avril 2003
Première soumission répondant aux critères de contrôle qualité
8 avril 2003
Première publication (Estimation)
9 avril 2003
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
2 juillet 2017
Dernière mise à jour soumise répondant aux critères de contrôle qualité
2 juin 2017
Dernière vérification
1 juin 2017
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Maladies cardiovasculaires
- Maladies vasculaires
- Maladies du système immunitaire
- Tumeurs par type histologique
- Tumeurs
- Troubles lymphoprolifératifs
- Maladies lymphatiques
- Troubles immunoprolifératifs
- Maladies hématologiques
- Troubles hémorragiques
- Troubles hémostatiques
- Paraprotéinémies
- Troubles des protéines sanguines
- Tumeurs, plasmocyte
- Leucémie, cellule B
- Lymphome
- Leucémie
- Macroglobulinémie de Waldenström
- Leucémie lymphocytaire chronique à cellules B
- Leucémie, Lymphoïde
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Inhibiteurs d'enzymes
- Agents antinéoplasiques
- Substances de croissance
- Inhibiteurs de croissance
- Inhibiteurs de protéine kinase
- Alvocidib
Autres numéros d'identification d'étude
- NCI-2012-01435 (Identificateur de registre: CTRP (Clinical Trial Reporting Program))
- P30CA016058 (Subvention/contrat des NIH des États-Unis)
- U01CA076576 (Subvention/contrat des NIH des États-Unis)
- CDR0000287197
- NCI-5746
- OSU-0055
- OSU 0055 (Autre identifiant: Ohio State University Medical Center)
- 5746 (Autre identifiant: CTEP)
- R21CA112947 (Subvention/contrat des NIH des États-Unis)
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 .