Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With Stage II-IV HIV-Associated Hodgkin Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01771107
First received: January 16, 2013
Last updated: September 16, 2014
Last verified: June 2014
  Purpose

This pilot phase I/II trial studies the side effects and the best dose of brentuximab vedotin and combination chemotherapy work in treating patients with stage II-IV human immunodeficiency virus (HIV)-associated Hodgkin lymphoma. Monoclonal antibodies, such as brentuximab vedotin, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as doxorubicin hydrochloride, vinblastine sulfate, and dacarbazine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving brentuximab vedotin together with combination chemotherapy may kill more cancer cells.


Condition Intervention Phase
HIV Infection
HIV-associated Hodgkin Lymphoma
Stage II Adult Hodgkin Lymphoma
Stage III Adult Hodgkin Lymphoma
Stage IV Adult Hodgkin Lymphoma
Drug: doxorubicin hydrochloride
Drug: vinblastine
Drug: dacarbazine
Drug: brentuximab vedotin
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Trial of AVD and Brentuximab Vedotin (SGN-35) in the Treatment of Stage II-IV HIV-Associated Hodgkin Lymphoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximal tolerated doses of brentuximab vedotin when combined with the AVD chemotherapy regimen in HIV patients with advanced stage Hodgkin lymphoma (Phase I) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Progression-free survival for patients using brentuximab vedotin plus AVD regimen with HIV-associated advanced stage Hodgkin lymphoma (Phase II) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Will be done using Kaplan-Meier estimates and corresponding 95% confidence intervals based on standard errors using Greenwood's formula.


Secondary Outcome Measures:
  • Frequency and severity of adverse events of AVD and brentuximab vedotin with HAART [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    The frequency of adverse events and their severity will be tabulated to evaluate tolerance of AVD and brentuximab vedotin with HAART.

  • Partial response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Binomial probabilities and their 95% confidence intervals will be used to estimate the response rates.

  • Partial response rate [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Binomial probabilities and their 95% confidence intervals will be used to estimate the response rates.

  • Complete response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Binomial probabilities and their 95% confidence intervals will be used to estimate the response rates.

  • Complete response rate [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Binomial probabilities and their 95% confidence intervals will be used to estimate the response rates.

  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Event-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Binomial probabilities and their 95% confidence intervals will be used to estimate the response rates (i.e., partial response rate, complete response rate, overall response rate) and event free survival at 2 and 5 years of AVD and brentuximab vedotin for a treatment of patients with stage III/IV HIV-associated Hodgkin Lymphoma.

  • Event-free survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Binomial probabilities and their 95% confidence intervals will be used to estimate the response rates (i.e., partial response rate, complete response rate, overall response rate) and event free survival at 2 and 5 years of AVD and brentuximab vedotin for a treatment of patients with stage III/IV HIV-associated Hodgkin Lymphoma.

  • Prognostic value of FDG-PET in patient with HIV and HL with respect to 2 year progression free survival [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Log-rank analysis will be used to investigate the prognostic value of FDG-PET scans at baseline, after 2 cycles and post-therapy in patients with HIV and HL with respect to progression free survival.

  • Prognostic value of FDG-PET in patient with HIV and HL with respect to 2 year progression free survival [ Time Frame: 8 weeks (after 2 courses) ] [ Designated as safety issue: No ]
    Log-rank analysis will be used to investigate the prognostic value of FDG-PET scans at baseline, after 2 cycles and post-therapy in patients with HIV and HL with respect to progression free survival.

  • Prognostic value of FDG-PET in patient with HIV and HL with respect to 2 year progression free survival [ Time Frame: 24 weeks (end of treatment) ] [ Designated as safety issue: No ]
    Log-rank analysis will be used to investigate the prognostic value of FDG-PET scans at baseline, after 2 cycles and post-therapy in patients with HIV and HL with respect to progression free survival.

  • HAART status [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Log-rank analysis will be used to evaluate HAART status at baseline for difference in outcome in terms of overall survival and progression free survival. The frequency and proportion of different histologic subtypes will be calculated.

  • Characterization of histologic subtypes in HIV-HL in the HAART era [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Incidence of neurotoxicity in combination with HAART and AVD and brentuximab vedotin [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Will be tabulated. A binomial test of proportions will be used to test the difference in additional toxicity between those patients taking AVD and brentuximab vedotin on HAART vs. those patients not on HAART.

  • Effect of AVD and brentuximab vedotin on viral load [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Repeated measures analysis of variance (ANOVA) models will be used to evaluate the effect of AVD and brentuximab vedotin on CD4 counts, CD8 counts and viral load after 1, 4, and 6 cycles, and every 3 months after treatment completion for one year.


Estimated Enrollment: 69
Study Start Date: March 2013
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (brentuximab and combination chemotherapy)
Patients receive doxorubicin hydrochloride IV, vinblastine sulfate IV, and dacarbazine IV on days 1 and 15. Patients also receive brentuximab vedotin IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
Drug: vinblastine
Given IV
Other Names:
  • Velban
  • Velsar
  • VLB
Drug: dacarbazine
Given IV
Other Names:
  • DIC
  • DTIC
  • DTIC-Dome
Drug: brentuximab vedotin
Given IV
Other Names:
  • Adcetris
  • anti-CD30 ADC SGN-35
  • anti-CD30 antibody-drug conjugate SGN-35
  • antibody-drug conjugate SGN-35
  • SGN-35
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infection, as documented by any federally approved, licensed HIV rapid test performed in conjunction with screening (or enzyme-linked immunosorbent assay [ELISA] test kit and confirmed by Western blot or other approved test); a measurable HIV viral load alone is not sufficient for documentation of the diagnosis of HIV; alternatively, this documentation may include a record that another physician has documented that the participant has HIV infection based on prior ELISA and western blot, or other approved diagnostic tests
  • Histologic diagnosis of CD30-positive classical HL as defined by the 2008 World Health Organization (WHO) Classification of Hematological diseases; nodular lymphocyte predominant Hodgkin Lymphoma is not eligible
  • Stage II, III or IV disease as defined by the Ann Arbor Staging System
  • Participants must have previously untreated HIV-classical HL (cHL), with the exception of up to 14 consecutive days of steroids or 1 prior cycle of cyclophosphamide to reduce tumor burden and improve hyperbilirubinemia in the setting of lymphoma related liver involvement
  • Normal baseline cardiac ejection fraction >= 50%
  • Serum creatinine of =< 1.5 mg/dL; if creatinine > 1.5 mg/dL, creatinine clearance must be >= 60 mL/minute
  • Absolute neutrophil count (ANC) >= 1000/uL
  • Platelets >= 75,000/uL unless related to bone marrow involvement by HIV-cHL
  • A direct bilirubin level of =< 2.0 mg/dL; if, however, the elevated bilirubin is felt to be secondary to antiretroviral therapy, the total bilirubin must be =< 3.5 mg/dL, provided that the direct bilirubin is normal and the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x the upper limit of normal; also, if the elevated bilirubin is thought to be secondary to cHL the patients should not be excluded from study participation
  • Female subjects must have a negative pregnancy test within 1 week of enrollment and all subjects must agree to use two reliable methods of contraception simultaneously if conception is possible during the study; should a woman subject become pregnant or suspect she is pregnant while the subject is participating in this study, she should inform her treating physician immediately; the patient will then be removed from protocol therapy; subjects who father a child while participating in the study will be permitted to continue with the protocol; the subject, however, is required to notify the investigator if he fathers a child
  • Ability to understand and the willingness to sign a written informed consent document
  • Karnofsky performance status > 30% (given the aggressiveness of this disease and the often severely debilitated nature of the patients at initial presentation)
  • Measurable or non-measurable (evaluable) tumor parameter(s); non-measurable tumor parameters will be defined as not having bi-dimensional measurements (i.e., gastric or marrow involvement) but can be followed for response by other diagnostic tests such as gallium, PET imaging and/or bone marrow biopsy
  • Patients already receiving erythropoietin or granulocyte colony stimulating factor (GCSF) for treatment of HIV-related cytopenia are eligible
  • CD4 count >= 50 cells/ul
  • Subjects are required to be on antiretroviral regimens that are in accordance with the current International acquired immune deficiency syndrome (AIDS) Society guidelines concurrently with chemotherapy; the specific agents are at the discretion of the Investigator and the use of investigational agents currently available on an expanded access basis is allowed; use of experimental antiretroviral agents or those containing zidovudine (including Combivir and Trizivir) or ritonavir (including Kaletra), cobicistat or similar potent cytochrome P450 (CYP)3 inhibitors are prohibited; in order to be eligible, patients taking zidovudine or ritonavir, or cobicistat or other CYP3 inhibitors must change to a different regimen 7 days prior to therapy initiation; changes to HAART during the study may be made if medically necessary (toxicity, failure of regimen, etc.); subjects must be on HAART at least 7 days prior to therapy
  • Patients will be required to obtain a pulmonary function test, despite the exclusion of bleomycin from protocol regimen; the subject's diffusing capacity of the lung for carbon monoxide (DLCO) adjusted for hemoglobin must be greater than 70% predicted to enter the study and to continue with brentuximab vedotin
  • Negative for hepatitis B, or infected with hepatitis B, receiving anti-hepatitis B therapy; all subjects will be required to be screened for hepatitis B; per Infectious Disease Society of America (IDSA) and American Association for the Study of Liver Diseases (AASLD) guidelines, those subjects that show no immunity, defined by the lack of hepatitis B surface antigen antibody, and show evidence of chronic infection (i.e. hepatitis B surface antigen [HBsAg]+, HBcore+, HBsAB-) will be required to be on anti-hepatitis B therapy, during the study, in order to be eligible; patients will be permitted to enroll in the study provided normal liver function tests and no evidence of cirrhosis; the exact hepatitis B therapy will be at the discretion of the infection disease specialist or investigator; however all patients who present with acute hepatitis B or show normal transaminases and are HBsAg+ and immunoglobulin M (IgM)+ for hepatitis core antigen will not be eligible for trial enrollment
  • Patients diagnosed with hepatitis C who are hepatitis C antibody positive, whether hepatitis C RNA level is measurable or not, must have no evidence of cirrhosis

Exclusion Criteria:

  • Patients with prior anthracycline therapy will be excluded
  • Female subjects who are pregnant or breast-feeding; confirmation that the subject is not pregnant must be established by a negative serum beta (b)-human chorionic gonadotropin (b-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women
  • Medical illness unrelated to HL, which in the opinion of the study physician will preclude administration of chemotherapy safely; this includes patients with uncontrolled infection (including opportunistic), chronic renal failure, myocardial infarction (MI) within the past 6 months, unstable angina, or cardiac arrhythmias other than chronic atrial fibrillation
  • Prior malignancy within 5 years of enrollment other than curatively treated cutaneous basal cell or squamous cell carcinoma, carcinoma in situ of the cervix, anal intraepithelial neoplasia, or cutaneous Kaposi's sarcoma (KS)
  • Grade 2 or greater peripheral neuropathy
  • Evidence of progressive multifocal leukoencephalopathy (PML) identified on the pretreatment magnetic resonance imaging (MRI)
  • Central nervous system disease
  • Patients with history of John Cunningham (JC) Virus identified in the cerebrospinal fluid (CSF) or previous history of PML will be excluded from the study
  • Cirrhosis secondary to any cause will be excluded
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01771107

Locations
United States, Georgia
Emory University/Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Mary Jo Lechowicz    404-778-3908    mlechow@emory.edu   
Principal Investigator: Mary Jo Lechowicz         
United States, Illinois
John H Stroger Jr Hospital of Cook County Recruiting
Chicago, Illinois, United States, 60612-3785
Contact: Paul G. Rubinstein    312-864-7277    prubinstein@cookcountyhhs.org   
Principal Investigator: Paul G. Rubinstein         
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Ariela Noy    212-639-7423    noya@mskcc.org   
Principal Investigator: Ariela Noy         
Sponsors and Collaborators
Investigators
Principal Investigator: Paul Rubinstein AIDS Associated Malignancies Clinical Trials Consortium
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01771107     History of Changes
Other Study ID Numbers: NCI-2013-00046, NCI-2013-00046, AMC-085, AMC-085, U01CA121947
Study First Received: January 16, 2013
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Hodgkin Disease
Lymphoma
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Antibodies
Antibodies, Monoclonal
Immunoconjugates
Doxorubicin
Liposomal doxorubicin
Vinblastine
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 16, 2014