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

This study is currently recruiting participants.
Verified April 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: April 9, 2014
Last verified: April 2014

January 16, 2013
April 9, 2014
March 2013
June 2018   (final data collection date for primary outcome measure)
  • 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 ]
Same as current
Complete list of historical versions of study NCT01771107 on ClinicalTrials.gov Archive Site
  • 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 AEs 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.
Same as current
Not Provided
Not Provided
 
Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With Stage II-IV HIV-Associated Hodgkin Lymphoma
A Pilot Trial of AVD and Brentuximab Vedotin (SGN-35) in the Treatment of Stage II-IV HIV-Associated Hodgkin Lymphoma

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.

PRIMARY OBJECTIVES I. To identify the maximum tolerated dose (MTD) of brentuximab vedotin when combined with the doxorubicin hydrochloride, vinblastine sulfate, and dacarbazine (AVD) chemotherapy regimen in the treatment of HIV-associated stage II-IV Hodgkin lymphoma. (Phase I) II. Establish an estimate of the two-year progression-free survival for patients with HIV-associated stage II-IV Hodgkin lymphoma when treated using brentuximab vedotin plus the AVD chemotherapy regimen. (Phase II)

SECONDARY OBJECTIVES:

I. To evaluate the toxicity of AVD and brentuximab vedotin with highly active antiretroviral therapy (HAART).

II. To estimate the partial response (PR) rate, complete response (CR) rate, overall survival (OS), and event free survival (EFS) at 2 and 5 years.

III. To evaluate the effect of AVD and brentuximab vedotin on CD4 and CD8 counts after cycle 1, 4, at the end of therapy, and every 3 months after treatment completion for one year.

IV. To investigate the prognostic value of fludeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) scans at baseline, after cycle 2, and at treatment completion, with respect to 2-year progression free survival.

V. To evaluate HAART status at baseline and to correlate this with tumor response to therapy and OS and progression-free survival (PFS).

VI. To characterize the histologic subtypes in HIV-Hodgkin lymphoma (HL) in the highly active antiretroviral therapy (HAART) era.

VII. To assess the neurotoxicity of HAART in combination with AVD and brentuximab vedotin.

VIII. To evaluate effect of AVD and brentuximab vedotin on viral load after cycle 1, 4, at the completion of therapy, and every 3 months after treatment completion for one year.

IX. To perform pharmacokinetic and immunogenicity studies to determine drug levels during therapy.

X. To perform micro ribonucleic acid (miRNA) profile analysis on the HIV-HL tumor specimens and to correlate miRNA expression with OS, PFS, tumor response to therapy, histologic subtype of HIV-HL, and HIV disease characteristics.

XI. To perform tissue microarray analysis on HIV-HL tumor specimens and to correlate the markers studied with OS, PFS, and tumor response to therapy.

XII. To identify Epstein-Barr virus (EBV)-associated tumor derived deoxyribonucleic acid (DNA) in the plasma of study patients and to correlate these levels during therapy with disease response and OS.(Phase II) XIII. To identify cytokines in the plasma of patients during therapy that can be used as tumor and prognostic markers.(Phase II) XIV. To assess latent and expressed HIV reservoirs before, during, and post chemotherapy. To understand how cytotoxic chemotherapeutic agents affect HIV expression.

OUTLINE:

Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on days 1 and 15. Patients also receive doxorubicin hydrochloride IV, vinblastine sulfate IV, and dacarbazine IV on days 1 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV Infection
  • HIV-associated Hodgkin Lymphoma
  • Stage II Adult Hodgkin Lymphoma
  • Stage III Adult Hodgkin Lymphoma
  • Stage IV Adult Hodgkin Lymphoma
  • 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
  • Drug: doxorubicin hydrochloride
    Given IV
    Other Names:
    • ADM
    • ADR
    • Adria
    • Adriamycin PFS
    • Adriamycin RDF
  • Drug: vinblastine
    Given IV
    Other Names:
    • Velban
    • Velsar
    • VLB
  • Drug: dacarbazine
    Given IV
    Other Names:
    • DIC
    • DTIC
    • DTIC-Dome
  • Other: pharmacological study
    Correlative studies
    Other Name: pharmacological studies
  • Other: laboratory biomarker analysis
    Correlative studies
Experimental: Treatment (brentuximab and combination chemotherapy)
Patients receive brentuximab vedotin IV over 30 minutes on days 1 and 15. Patients also receive doxorubicin hydrochloride IV, vinblastine sulfate IV, and dacarbazine IV on days 1 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Drug: brentuximab vedotin
  • Drug: doxorubicin hydrochloride
  • Drug: vinblastine
  • Drug: dacarbazine
  • Other: pharmacological study
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
51
Not Provided
June 2018   (final data collection date for primary outcome measure)

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 weeks 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, positron emission tomography (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 shows 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 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
Both
18 Years and older
No
Not Provided
United States
 
NCT01771107
NCI-2013-00046, NCI-2013-00046, AMC-085, AMC-085, U01CA121947
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Paul Rubinstein AIDS Associated Malignancies Clinical Trials Consortium
National Cancer Institute (NCI)
April 2014

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