Bryostatin 1 and High Dose Cytarabine in Treating Patients With Refractory or Relapsed Leukemia or Lymphoma
Phase I Study of Bryostatin 1 (NSC 339555) and High-Dose 1-Beta-D-Arabinofuranosylcytosine (HiDAC) in Patients With Refractory Leukemia
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.
PURPOSE: Phase I trial to study the effectiveness of bryostatin 1 and high dose cytarabine in treating patients with refractory or relapsed acute myelocytic or acute lymphocytic leukemia, chronic myelogenous leukemia or refractory or relapsed lymphoblastic lymphoma.
Panoramica dello studio
Stato
Intervento / Trattamento
Descrizione dettagliata
OBJECTIVES: I. Define the maximum tolerated dose (MTD) of bryostatin 1 administered before and after high dose cytarabine in patients with refractory or relapsed acute myelocytic leukemia or acute lymphocytic leukemia, chronic myelogenous leukemia, or refractory or relapsed lymphoblastic lymphoma. II. Describe the toxic effects of bryostatin 1 and high dose cytarabine in these patients. III. Describe the time course of bryostatin 1 induced modulation of leukemic blast total protein kinase C (PKC) activity. IV. Describe bryostatin 1 pharmacokinetics. V. Correlate bryostatin 1 induced modulation of leukemic cell PKC activity or leukemic cell maturation with high dose cytarabine mediated apoptosis.
OUTLINE: This is a dose escalation study. Patients receive bryostatin 1 by continuous infusion over 24 hours on day 1. One hour after completion of bryostatin 1, patients receive high dose cytarabine IV over 3 hours every 12 hours on days 2-4. Patients again receive cytarabine over 3 hours every 12 hours on days 9-11, followed 1 hour later by bryostatin 1 by continuous infusion over 24 hours beginning on day 11. Patients achieving complete remission may receive up to 4 courses of consolidation chemotherapy. Consolidation chemotherapy is the same as induction chemotherapy except patients receive only 2 doses of cytarabine after day 1 completion of bryostatin and only 2 doses of cytarabine prior to the day 11 dose of bryostatin. Patients achieving partial remission may receive a second course of induction chemotherapy. In the absence of dose limiting toxicity in the first 3 patients treated, subsequent cohorts of 6 patients receive escalating doses of bryostatin 1 on the same schedule. If dose limiting toxicity occurs in 2 of 6 patients at a given dose level, then dose escalation ceases and the current dose is defined as the maximum tolerated dose. Patients are followed every 6 months until death.
PROJECTED ACCRUAL: A total of 12-50 patients will be accrued for this study.
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 1
Contatti e Sedi
Luoghi di studio
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New York
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New York, New York, Stati Uniti, 10021
- New York Presbyterian Hospital - Cornell Campus
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Texas
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Houston, Texas, Stati Uniti, 77030
- University of Texas - MD Anderson Cancer Center
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Virginia
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Richmond, Virginia, Stati Uniti, 23298-0037
- Massey Cancer Center
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
DISEASE CHARACTERISTICS: Histologically confirmed primary refractory or relapsed acute myelocytic leukemia (AML) or acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML) in blast crisis, or refractory or relapsed lymphoblastic lymphoma Priority is given to patients previously treated with conventional high dose cytarabine regimen without bryostatin 1 Eligible if previously failed a conventional high dose cytarabine regimen or if underwent subsequent high dose therapy with bone marrow/stem cell transplantation with curative intent
PATIENT CHARACTERISTICS: Age: 18 and over (must be 60 or under if receiving higher dose of cytarabine) Performance status: Karnofsky 60-100% Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2.0 mg/dL (bilirubin no greater than 3.0 mg/dL and conjugated bilirubin no greater than 0.5 mg/dL if Gilbert's disease and predominantly unconjugated hyperbilirubinemia present) AST no greater than 2.5 times upper limit of normal (ULN) Alkaline phosphatase no greater than 2.5 times ULN Renal: Creatinine clearance at least 40 mL/min (at least 60 mL/min if receiving higher dose of cytarabine) Pulmonary: No clinically significant pulmonary disease Other: Not pregnant No patients who are poor medical risks because of nonmalignant systemic disease No serious, active, uncontrolled infection No prior or concurrent medical status that would make assessing cortical or cerebellar neurologic toxicity difficult
PRIOR CONCURRENT THERAPY: Recovery from the major toxic effects of prior therapy required Biologic therapy: See Disease Characteristics Chemotherapy: See Disease Characteristics At least 24 hours since prior chemotherapy with hydroxyurea At least 3 weeks since other prior systemic chemotherapy No prior clinically significant cerebellar toxicity due to cytarabine Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione fattoriale
- Mascheramento: Nessuno (etichetta aperta)
Collaboratori e investigatori
Sponsor
Collaboratori
Investigatori
- Cattedra di studio: Steven Grant, MD, Massey Cancer Center
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Malattie del sistema immunitario
- Neoplasie per tipo istologico
- Neoplasie
- Malattie linfoproliferative
- Malattie linfatiche
- Disturbi immunoproliferativi
- Linfoma
- Leucemia
- Effetti fisiologici delle droghe
- Meccanismi molecolari dell'azione farmacologica
- Agenti antinfettivi
- Agenti antivirali
- Antimetaboliti, Antineoplastici
- Antimetaboliti
- Agenti antineoplastici
- Agenti immunosoppressivi
- Fattori immunologici
- Adiuvanti, immunologici
- Citarabina
- Briostatina 1
Altri numeri di identificazione dello studio
- CDR0000065773
- P30CA016059 (Sovvenzione/contratto NIH degli Stati Uniti)
- MCV-MCC-9612-2E
- NCI-T97-0011
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
prodotto fabbricato ed esportato dagli Stati Uniti
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