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Brentuximab Vedotin Before Autologous Stem Cell Transplant in Treating Patients With Hodgkin Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by City of Hope Medical Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT01393717
First received: July 8, 2011
Last updated: October 30, 2014
Last verified: October 2014

July 8, 2011
October 30, 2014
October 2011
December 2015   (final data collection date for primary outcome measure)
  • Overall response rate of salvage brentuximab vedotin treatment for Hodgkin lymphoma before autologous hematopoietic stem cell transplantation [ Time Frame: 21 days after completion of last course of study treatment ] [ Designated as safety issue: No ]
    The study will utilize a Simon two-stage optimal design. Response rates will be calculated as the percent of evaluable patients that have confirmed complete response (CR) or partial response (PR) by radiographic response including CT and/or PET scans, and exact 95% confidence intervals will be calculated for this estimate. Time to response, duration of response, and survival will be estimated using the product-limit method of Kaplan and Meier.
  • CR rate (new cohort) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
Efficacy of this salvage brentuximab vedotin treatment for Hodgkin lymphoma before autologous hematopoietic stem cell transplantation [ Time Frame: 21 days after completion of last course of study treatment ] [ Designated as safety issue: No ]
Measured by the ORR. The study will utilize a Simon two-stage optimal design. Response rates will be calculated as the percent of evaluable patients that have confirmed complete response (CR) or partial response (PR) by radiographic response including CT and/or PET scans, and exact 95% confidence intervals will be calculated for this estimate. Time to response, duration of response, and survival will be estimated using the product-limit method of Kaplan and Meier.
Complete list of historical versions of study NCT01393717 on ClinicalTrials.gov Archive Site
  • Safety, toxicity, and tolerability of brentuximab vedotin as a salvage regimen as determined by incidence of adverse events and lab abnormalities [ Time Frame: Through 21 days after completion of study treatment ] [ Designated as safety issue: Yes ]
    Toxicity will be assessed using the National Institute of Health-National Cancer Institute (NIH-NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0. Toxicity information recorded will include the type, severity, and the probable association with the study regimen. Tables will be constructed to summarize the observed incidence by severity and type of toxicity.
  • Stem cell mobilization results of patients receiving brentuximab vedotin as salvage therapy for patients that are proceeding to autologous hematopoietic stem cell transplantation [ Time Frame: 60 days after completion of last course of study treatment ] [ Designated as safety issue: No ]
  • Potential changes in Hodgkin lymphoma biological markers of patients treated with brentuximab vedotin [ Time Frame: 21 days after completion of study treatment ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Assessed for up to 4 years ] [ Designated as safety issue: No ]
    Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formula.
  • OS defined as the time from first treatment day (post AHCT) until death [ Time Frame: Assessed for up to 4 years ] [ Designated as safety issue: No ]
    Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formula.
  • Safety, toxicity, and tolerability of brentuximab vedotin as a salvage regimen as determined by incidence of adverse events and lab abnormalities [ Time Frame: Through 21 days after completion of study treatment ] [ Designated as safety issue: Yes ]
  • Stem cell mobilization results of patients receiving brentuximab vedotin as salvage therapy for patients that are proceeding to autologous hematopoietic stem cell transplantation [ Time Frame: 60 days after completion of last course of study treatment ] [ Designated as safety issue: No ]
  • Potential changes in Hodgkin lymphoma biological markers of patients treated with brentuximab vedotin [ Time Frame: 21 days after completion of study treatment ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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

This phase II trial studies how well brentuximab vedotin before autologous (taken from an individual's own cells) stem cell transplant works in treating patients with Hodgkin lymphoma. Monoclonal antibody-drug conjugates, such as brentuximab vedotin, can block cancer growth in different ways by targeting certain cells.

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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Recurrent Adult Hodgkin Lymphoma
  • Recurrent/Refractory Childhood Hodgkin Lymphoma
  • Drug: brentuximab vedotin
    Given IV
    Other Names:
    • anti-CD30 ADC SGN-35
    • anti-CD30 antibody-drug conjugate SGN-35
    • antibody-drug conjugate SGN-35
    • SGN-35
    • Adcetris
  • Other: laboratory biomarker analysis
    Correlative studies
  • Genetic: protein expression analysis
    Correlative studies
Experimental: 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.
Interventions:
  • Drug: brentuximab vedotin
  • Other: laboratory biomarker analysis
  • Genetic: protein expression analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
57
Not Provided
December 2015   (final data collection date for primary outcome measure)

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)
  • Creatinine up to and including 2 mg/dL (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&apos;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.
Both
11 Years and older
No
United States
 
NCT01393717
11051, NCI-2011-01135
Yes
City of Hope Medical Center
City of Hope Medical Center
National Cancer Institute (NCI)
Principal Investigator: Robert Chen City of Hope Medical Center
City of Hope Medical Center
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP