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

NCT01393717 | Completed Phase 2 Results DMC

• 2 other identifiers: 11051NCI-2011-01135
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 2

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.

Conditions

Recurrent Hodgkin Lymphoma; Refractory Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (4)

• Overall Response Rate Among Patients With Salvage Brentuximab Vedotin (BV)

  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.

  21 days after completion of last course of study treatment, up to 5 years

• Complete Response (CR) Rate Among Patients With Salvage Brentuximab Vedotin (BV)

  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

  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.

  21 days after completion of last course of study treatment, up to 5 years

• Complete Response (CR) Rate in Cohort #2

  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

Secondary Outcomes (3)

• Total CD34+ Cell Dose Among Patients Receiving Brentuximab Vedotin Followed by Autologous Hematopoietic Stem Cell Transplantation

  60 days after completion of last course of study treatment, up to conditioning regimens

• Progression Free Survival at Year Two Among AutoHCT Patients With BV

  Assessed for up to 5 years, at least half of the surviving participants followed 2+ years

• Overall Survival at Year Two Among AutoHCT Patients With BV

  Assessed for up to 5 years, at least half of the surviving participants followed 2+ years

Study Arms (1)

Treatment (brentuximab vedotin)

EXPERIMENTAL

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.

Drug: brentuximab vedotin

Interventions

brentuximab vedotin DRUG

Given IV

Also known as: anti-CD30 ADC SGN-35, anti-CD30 antibody-drug conjugate SGN-35, antibody-drug conjugate SGN-35, SGN-35, Adcetris

Treatment (brentuximab vedotin)

Eligibility Criteria

• Age: 11 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Weill Medical College, Cornell University

New York, New York, 10065, United States

Location

Related Publications (2)

• 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.

  PMID: 29272364 DERIVED

• 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.

  PMID: 26211987 DERIVED

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Brentuximab Vedotin

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Robert Chen
• Organization: City of Hope National Medical Center

RChen@coh.org

626-256-4673

Study Officials

• Robert Chen

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2011
• First Posted: July 13, 2011
• Study Start: October 20, 2011
• Primary Completion: February 1, 2017
• Study Completion: February 1, 2017
• Last Updated: April 26, 2018
• Results First Posted: April 26, 2018

Record last verified: 2018-03

Locations

US (2)