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

NCT ID: NCT01393717

Last Updated: 2018-04-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-20
• Study Completion Date: 2017-02-01

Brief Summary

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.

Detailed Description

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.

Conditions

Recurrent Hodgkin Lymphoma; Refractory Hodgkin Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

brentuximab vedotin

Intervention Type: DRUG

Given IV

Interventions

brentuximab vedotin

Given IV

Intervention Type: DRUG

Other Intervention Names

anti-CD30 ADC SGN-35; anti-CD30 antibody-drug conjugate SGN-35; antibody-drug conjugate SGN-35; SGN-35; Adcetris

Eligibility Criteria

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:

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.

• Minimum Eligible Age: 11 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Chen

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

City of Hope Medical Center

Duarte, California, United States

Weill Medical College, Cornell University

New York, New York, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 29272364 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26211987 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2011-01135

Identifier Type: REGISTRY

Identifier Source: secondary_id

11051

Identifier Type: -

Identifier Source: org_study_id