- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT00538187
Obatoclax and Bortezomib in Treating Patients With Aggressive Relapsed or Recurrent Non-Hodgkin Lymphoma
Phase I Study of GX15-070 (NSC # 729280) and Bortezomib in Aggressive Relapsed/Recurrent Non-Hodgkin's Lymphoma
Studieoversigt
Status
Betingelser
- Tilbagevendende voksent diffust storcellet lymfom
- Tilbagevendende grad 1 follikulært lymfom
- Tilbagevendende grad 2 follikulært lymfom
- Tilbagevendende grad 3 follikulært lymfom
- Tilbagevendende kappecellelymfom
- Tilbagevendende marginalzone lymfom
- Tilbagevendende lille lymfocytisk lymfom
- Voksen non-Hodgkin lymfom
Intervention / Behandling
Detaljeret beskrivelse
PRIMARY OBJECTIVES:
I. To establish the maximum tolerated dose of obatoclax mesylate when administered with bortezomib in patients with aggressive relapsed or recurrent non-Hodgkin lymphoma.
II. To describe the toxicities of this regimen at each dose studied in these patients.
III. To characterize the pharmacokinetic behavior of this regimen in these patients.
IV. To obtain preliminary information regarding the effect of obatoclax mesylate on several apoptotic regulatory pathways.
V. To document all clinical responses in these patients to this regimen.
OUTLINE: This is a multicenter study.
PHASE I: Patients receive obatoclax mesylate IV over 3 hours followed by bortezomib IV on days 1, 8, 15, and 22.
Treatment repeats every 35 days in the absence of disease progression or unacceptable toxicity. Pharmacokinetic evaluations of obatoclax mesylate are conducted in all patients during the first course.
PHASE II: Patients receive obatoclax mesylate IV over 3 hours followed by bortezomib IV on days 1, 8, 15, and 22 at the maximum tolerated dose determined in phase I.
Treatment repeats every 35 days for up to 1 year in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed for 26 weeks.
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 1
Kontakter og lokationer
Studiesteder
-
-
California
-
Duarte, California, Forenede Stater, 91010
- City of Hope Medical Center
-
-
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
Histologically or cytologically confirmed relapsed or refractory non-Hodgkin lymphoma for which standard curative or palliative measures do not exist or are no longer effective, including any of the following subtypes:
- Follicular grade I, II, or III lymphoma
- Marginal zone lymphoma
- Mantle cell lymphoma
- Diffuse large B cell lymphoma
- Small lymphocytic lymphoma
Must have had at least one prior chemotherapeutic regimen:
- Steroids or rituximab alone or local radiotherapy do not count as regimens
- Tositumomab or ibritumomab tiuxetan allowed as regimens
- Clear evidence of disease progression or lack of response after the most recent therapy, including rituximab or local radiotherapy, is required
- At least 3 months since prior autologous stem cell transplantation and relapsed (>= 1 year since prior allogeneic transplantation and relapsed) and no active related infections (i.e., fungal or viral)
- In the case of allogeneic transplantation relapse, there should be no active acute graft-versus-host disease (GVHD) of any grade and no chronic GVHD other than mild skin, oral, or ocular GVHD not requiring systemic immunosuppression
- No known active brain metastases, other neurological disorders/dysfunction or history of seizure disorder, or other neurological dysfunction
- Karnofsky performance status 60-100%
- Life expectancy > 3 months
- Total bilirubin normal
- AST and ALT =< 2.5 times upper limit of normal
- Creatinine normal or creatinine clearance >= 60 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective double-barrier contraception during and for 3 months after the last dose of obatoclax mesylate
- At least 4 weeks since prior radiotherapy
- More than 2 days since prior steroids
- More than 2 weeks since prior low-dose chlorambucil
- WBC >= 3,000/mm^3
- ANC >= 1,500/mm^3
- Platelet count >= 100,000/mm^3
- At least 2 weeks since prior valproic acid
Exclusion Criteria:
Uncontrolled concurrent medical condition or illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia including QTc > 450 msec
- Patients who are intolerant or refractory to prior treatment with bortezomib (refractory is defined as no response to prior treatment with bortezomib)
- Chemotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C)
- Rituximab within the past 3 months (unless there is evidence of progression)
- Patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Other concurrent investigational agents
- Combination antiretroviral therapy for HIV-positive patients
- No history of allergic reactions attributed to bortezomib, polyethylene glycol (PEG 300), or polysorbate 20
- No psychiatric illness or social situation that would limit compliance with study requirements
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
---|---|
Eksperimentel: Treatment (obatoclax mesylate, bortezomib)
Patients will receive a 3-hour infusion of obatoclax and an infusion of bortezomib once a week for 4 weeks
|
Givet IV
Andre navne:
korrelativ undersøgelse
Andre navne:
korrelativ undersøgelse
Givet IV
Andre navne:
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Maximum tolerated dose of obatoclax mesylate when administered with bortezomib
Tidsramme: 35 days
|
Defined as the highest dose tested in which fewer than 33% of patients experienced DLT attributable to the study drug(s), when at least six patients were treated at that dose and are evaluable for toxicity.
Graded according to the NCI CTCAE, Version 3.0.
|
35 days
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Toxicity as assessed by NCI CTCAE version 3.0
Tidsramme: Up to 26 weeks after completion of study treatment
|
Summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity and nadir or maximum values for the laboratory measures, time of onset (i.e.
course number), duration, and reversibility or outcome.
Tables will be created to summarize these toxicities and side effects by dose and by course.
|
Up to 26 weeks after completion of study treatment
|
Pharmacokinetics of obatoclax mesylate when administered with bortezomib
Tidsramme: Dose 1 of course 1, pre-infusion, 1 and 2 hours into the infusion, immediately prior to the end of the infusion, then at 0.25, 0.5, 1, 2, 4, 8, 24, 48, 72, and 168 hours
|
Dose 1 of course 1, pre-infusion, 1 and 2 hours into the infusion, immediately prior to the end of the infusion, then at 0.25, 0.5, 1, 2, 4, 8, 24, 48, 72, and 168 hours
|
Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Ledende efterforsker: Joseph Tuscano, City of Hope Medical Center
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Patologiske processer
- Sygdomme i immunsystemet
- Neoplasmer efter histologisk type
- Neoplasmer
- Lymfoproliferative lidelser
- Lymfesygdomme
- Immunproliferative lidelser
- Sygdomsegenskaber
- Leukæmi, lymfoid
- Leukæmi
- Leukæmi, B-celle
- Lymfom, B-celle
- Lymfom
- Lymfom, follikulært
- Lymfom, stor B-celle, diffus
- Tilbagevenden
- Lymfom, Non-Hodgkin
- Lymfom, kappecelle
- Leukæmi, lymfatisk, kronisk, B-celle
- Molekylære mekanismer for farmakologisk virkning
- Enzymhæmmere
- Antineoplastiske midler
- Bortezomib
- Obatoclax
Andre undersøgelses-id-numre
- NCI-2009-00253
- U01CA062505 (U.S. NIH-bevilling/kontrakt)
- PHI-58
- CDR0000566357
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .
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