- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT01393717
Brentuximab Vedotin Before Autologous Stem Cell Transplant in Treating Patients With Hodgkin Lymphoma
A Phase II Study of Brentuximab Vedotin as Salvage Therapy for Hodgkin Lymphoma Prior to Autologous Hematopoietic Stem Cell Transplantation
Přehled studie
Postavení
Intervence / Léčba
Detailní popis
PRIMARY OBJECTIVES:
I. The primary objective of this study is to determine the activity of salvage brentuximab vedotin in Hodgkin lymphoma prior to autologous hematopoietic stem cell transplantation, as measured by overall response rate (ORR).
SECONDARY OBJECTIVES:
I. To describe the safety, toxicity, and tolerability of brentuximab vedotin as a salvage regimen.
II. To summarize the stem cell mobilization results of patients receiving brentuximab vedotin as salvage therapy (e.g., total cluster of differentiation (CD)34+ cell yield, number of apheresis days, proportion of patients who achieve >= 3 x 10^6 CD34+ cells/kg).
III. To evaluate potential changes in Hodgkin lymphoma biological markers of patients treated with brentuximab vedotin as first line salvage therapy.
IV. To examine and characterize the outcomes of patients who receive brentuximab vedotin as first line salvage followed by autologous hematopoietic stem cell transplantation (AHCT) (e.g., toxicity, 2-year progression free survival [PFS], overall survival [OS], relapse-progression incidence and non-relapse mortality rate [NRM])
OUTLINE:
Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 courses.
Patients in the new cohort receive regular study dose of brentuximab vedotin for courses 1 and 2. Patients not achieving complete remission (CR) after 2 courses receive higher-dose brentuximab vedotin IV over 60 minutes on day 1 for 2 additional courses.
After completion of study treatment, patients are followed up at 21 days.
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 2
Kontakty a umístění
Studijní místa
-
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California
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Duarte, California, Spojené státy, 91010
- City of Hope Medical Center
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New York
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New York, New York, Spojené státy, 10065
- Weill Medical College, Cornell University
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- Patients must have histologically documented or cytologically confirmed Hodgkin lymphoma with CD 30 expression
- Patients must have absolute neutrophil count (ANC) >= 1000/uL; neupogen (filgrastim) can be given prior to start of SGN-35 (brentuximab vedotin) and during SGN-35 treatment to achieve target ANC >= 1000/uL
- Patients must have platelets (Plts) >= 50,000/uL; platelet transfusion can be given prior to the start of SGN-35 and during SGN-35 treatment to achieve a target plt >= 50,000/uL
- Patients must have measurable disease > 1.5 cm evidenced by computed tomography (CT) scan of the neck/chest/abdomen(abd)/pelvis or CT/positron emission tomography (PET) scans
- Patient must be either primary refractory to one frontline induction therapy or relapsed after one frontline induction therapy; patients who do not achieve complete remission after induction therapy are also eligible
- Patients cannot have had a second line salvage treatment (chemotherapy, biologic agents, investigational drugs, or radiation) or have had an autologous or allogeneic hematopoietic stem cell transplantation; patients can have had mixed frontline therapy such as 2-4 cycles of ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) followed by 2-4 cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) as long as the induction chemotherapy is not more than 8 cycles in total length
- Radiation use as part of induction regimen or consolidation (within 90 days after completion of induction chemotherapy) is allowed
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
- Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study
- Male subject agrees to use an acceptable method of contraception for the duration of the study
- Life expectancy of greater than 3 months
- Karnofsky performance status of > 60%
- ANC >= 1000/uL
- Plts >= 50,000/uL
- Total bilirubin within 1.5 x of the upper limit of normal (ULN) institutional limits, patients with elevation of unconjugated bilirubin alone, as in Gilbert's disease, are eligible
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 X institutional ULN (unless demonstrated Hodgkin lymphoma involvement of the liver)
- Calculated creatinine clearance >30 ml/min (unless demonstrated Hodgkin lymphoma involvement of the kidney)
ELIGIBILITY FOR 2.4 MG/KG DOSING IN THE NEW COHORT:
- In addition to the inclusion/exclusion criteria outlined, to be eligible for treatment with the higher 2.4 mg/kg dose of brentuximab vedotin in the new cohort of 20 additional patients, best response after 2 cycles of brentuximab vedotin administered at the 1.8 mg/kg dose, must be partial remission (PR) or stable disease (SD) as determined by radiographic imaging
Exclusion Criteria:
- Patient has > 1.5 x ULN total bilirubin, unless history of Gilbert's syndrome
- Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
- Patient has hypersensitivity to brentuximab vedotin
- Female subject is pregnant or breast-feeding; confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women
- Patient has received other investigational drugs within 14 days before treatment of treatment with brentuximab vedotin
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study
- Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy
- Patients with other active malignancies (no evidence of other cancer or life expectancy greater than 5 years) are ineligible for this study
- Patients with active central nervous system (CNS) disease or history of brain metastases (mets) are excluded from study
- Patients may be on steroids prior to initiation of treatment as long as by cycle 1 day 1 steroids use was tapered down less than or equal to 20 mg of prednisone.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: Treatment (brentuximab vedotin)
Patients receive brentuximab vedotin IV over 30 minutes on day 1.
Treatment repeats every 21 days for up to 4 courses.
Patients in the new cohort receive regular study dose of brentuximab vedotin for courses 1 and 2. Patients not achieving CR after 2 courses receive higher-dose brentuximab vedotin IV over 60 minutes on day 1 for 2 additional courses.
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Vzhledem k tomu, IV
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Overall Response Rate Among Patients With Salvage Brentuximab Vedotin (BV)
Časové okno: 21 days after completion of last course of study treatment, up to 5 years
|
The overall response rate is calculated as the percent of evaluable patients that have confirmed CR or PR by radiographic imaging, and the exact 95% confidence interval is calculated for this estimate.
Per Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007) for target lesions and assessed by CT/PET scans: Complete Response (CR), complete disappearance of all detectable clinical and radiographic evidence of disease; Partial Response (PR), ≥50% decrease in the sum of the product of the diameters of up to six of the largest dominant nodes or nodal masses.
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21 days after completion of last course of study treatment, up to 5 years
|
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Complete Response (CR) Rate Among Patients With Salvage Brentuximab Vedotin (BV)
Časové okno: 21 days after completion of last course of study treatment, up to 5 years
|
The CR rate is calculated as the percent of evaluable patients that have confirmed CR by radiographic imaging, and the exact 95% confidence interval is calculated for this estimate.
Per Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007) for target lesions and assessed by CT/PET scans: Complete Response (CR), complete disappearance of all detectable clinical and radiographic evidence of disease.
|
21 days after completion of last course of study treatment, up to 5 years
|
|
Overall Response Rate in Cohort #2
Časové okno: 21 days after completion of last course of study treatment, up to 5 years
|
The overall response rate is calculated as the percent of evaluable patients that have confirmed CR or PR by radiographic imaging, and the exact 95% confidence interval is calculated for this estimate.
Per Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007) for target lesions and assessed by CT/PET scans: Complete Response (CR), complete disappearance of all detectable clinical and radiographic evidence of disease; Partial Response (PR), ≥50% decrease in the sum of the product of the diameters of up to six of the largest dominant nodes or nodal masses.
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21 days after completion of last course of study treatment, up to 5 years
|
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Complete Response (CR) Rate in Cohort #2
Časové okno: 21 days after completion of last course of study treatment, up to 5 years
|
The CR rate is calculated as the percent of evaluable patients that have confirmed CR by radiographic imaging, and the exact 95% confidence interval is calculated for this estimate.
Per Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007) for target lesions and assessed by CT/PET scans: Complete Response (CR), complete disappearance of all detectable clinical and radiographic evidence of disease.
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21 days after completion of last course of study treatment, up to 5 years
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Total CD34+ Cell Dose Among Patients Receiving Brentuximab Vedotin Followed by Autologous Hematopoietic Stem Cell Transplantation
Časové okno: 60 days after completion of last course of study treatment, up to conditioning regimens
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Among the patients receiving salvage Brentuximab Vedotin (BV) followed by Autologous Hematopoietic Stem Cell Transplantation (AutoHCT), their total CD34+ cell yield by stem cell mobilization.
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60 days after completion of last course of study treatment, up to conditioning regimens
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Progression Free Survival at Year Two Among AutoHCT Patients With BV
Časové okno: Assessed for up to 5 years, at least half of the surviving participants followed 2+ years
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Progression Free Survival (PFS) defined as the time from first treatment day (post AHCT) until objective or symptomatic relapse or death as a result of lymphoma or acute toxicity of treatment.
Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formula.
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Assessed for up to 5 years, at least half of the surviving participants followed 2+ years
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Overall Survival at Year Two Among AutoHCT Patients With BV
Časové okno: Assessed for up to 5 years, at least half of the surviving participants followed 2+ years
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Overall Survival (OS) defined as the time from first treatment day (post AHCT) until death.
Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formula.
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Assessed for up to 5 years, at least half of the surviving participants followed 2+ years
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Spolupracovníci a vyšetřovatelé
Sponzor
Spolupracovníci
Vyšetřovatelé
- Vrchní vyšetřovatel: Robert Chen, City of Hope Medical Center
Publikace a užitečné odkazy
Obecné publikace
- Herrera AF, Palmer J, Martin P, Armenian S, Tsai NC, Kennedy N, Sahebi F, Cao T, Budde LE, Mei M, Siddiqi T, Popplewell L, Rosen ST, Kwak LW, Nademanee A, Forman SJ, Chen R. Autologous stem-cell transplantation after second-line brentuximab vedotin in relapsed or refractory Hodgkin lymphoma. Ann Oncol. 2018 Mar 1;29(3):724-730. doi: 10.1093/annonc/mdx791.
- Chen R, Palmer JM, Martin P, Tsai N, Kim Y, Chen BT, Popplewell L, Siddiqi T, Thomas SH, Mott M, Sahebi F, Armenian S, Leonard J, Nademanee A, Forman SJ. Results of a Multicenter Phase II Trial of Brentuximab Vedotin as Second-Line Therapy before Autologous Transplantation in Relapsed/Refractory Hodgkin Lymphoma. Biol Blood Marrow Transplant. 2015 Dec;21(12):2136-2140. doi: 10.1016/j.bbmt.2015.07.018. Epub 2015 Jul 26.
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
- Onemocnění imunitního systému
- Novotvary podle histologického typu
- Novotvary
- Lymfoproliferativní poruchy
- Lymfatická onemocnění
- Imunoproliferativní poruchy
- Lymfom
- Hodgkinova nemoc
- Fyziologické účinky léků
- Antineoplastická činidla
- Imunologické faktory
- Antineoplastická činidla, Imunologická
- Protilátky
- Imunoglobuliny
- Monoklonální protilátky
- Brentuximab vedotin
- Imunokonjugáty
Další identifikační čísla studie
- 11051
- NCI-2011-01135 (Identifikátor registru: CTRP (Clinical Trial Reporting Program))
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