A Pilot Trial of AVD and Brentuximab Vedotin (SGN-35) in the Treatment of Stage III-IV HIV-associated Hodgkin Lymphoma

• Register: ClinicalTrials.gov
• Last refreshed on: 3 October 2023
• Main ID: NCT02298257
• Date of registration: 13/11/2014
• Prospective Registration: Yes
• Primary sponsor: The Lymphoma Academic Research Organisation
• Public title: A Pilot Trial of AVD and Brentuximab Vedotin (SGN-35) in the Treatment of Stage III-IV HIV-associated Hodgkin Lymphoma AMC-085
• Scientific title: A Pilot Trial of AVD and Brentuximab Vedotin (SGN-35) in the Treatment of Stage III-IV HIV-associated Hodgkin Lymphoma
• Date of first enrolment: June 2015
• Target sample size: 9
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02298257
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

France

Contacts

• Name: Caroline Besson, MD
• Affiliation: Lymphoma Study Association

• Name: Nicolas Mounier, Pr
• Affiliation: Lymphoma Study Association

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Age = 18 years. Because no dosing or adverse event data are currently available on the
use of brentuximab vedotin in combination with AVD in patients <18 years of age,
children are excluded from this study

2. HIV-1 infection, as documented by licensed HIV rapid test performed in conjunction
with screening (or 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

3. Histologic diagnosis of CD30-positive classical HL as defined by the 2008 WHO
Classification of Hematological diseases. Nodular lymphocyte predominant Hodgkin
Lymphoma is not eligible

4. Stage III or IV disease as defined by the Ann Arbor Staging System

5. Participants must have previously untreated HIV-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

6. Normal baseline cardiac ejection fraction = 50%

7. Serum creatinine of = 1.5 mg/dL. If creatinine >1.5 mg/dL (132 micromol/L), creatinine
clearance must be = 60 mL/minute according to MDRD/Cockroft-Gault formula

8. ANC = 1000/µL and platelets = 75,000/µL unless related to bone marrow involvement by
HIV-cHL

9. A direct bilirubin level of = 2.0 mg/dL (34 µmol/L). If, however, the elevated
bilirubin is felt to be secondary to antiretroviral therapy, the total bilirubin must
be = 3.5 mg/dL (59 µmol/L), provided that the direct bilirubin is normal and the AST
and 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

10. 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

11. Ability to understand and the willingness to sign a written informed consent document

12. Karnofsky performance status > 30% (given the aggressiveness of this disease and the
often severely debilitated nature of the patients at initial presentation). See
Appendix 20.519.5

13. 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

14. Patients already receiving erythropoietin or GCSF for treatment of HIV-related
cytopenia are eligible

15. CD4 count = 100 cells/µl and serum HIV viral load <50copies/ml

16. Subjects are required to be on antiretroviral regimens that are in accordance with the
current International AIDS Society guidelines concurrently with chemotherapy. Use of
experimental antiretroviral agents or those containing zidovudine or ritonavir,
cobicistat or similar potent CYP3 inhibitors are prohibited, as explained in Section
5.7. 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. Subjects must be on HAART for at least 12 weeks prior to therapy. See
section 10.3

17. 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

18. Negative for Hepatitis B, or if infected with Hepatitis B, receiving anti-Hepatitis B
therapy. All subjects will be required to be screened for Hepatitis B. Per IDSA and
AASD guidelines, those subjects that show no immunity, defined by the lack of
Hepatitis B surface antibody, and show evidence of chronic infection (i.e., 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 (see Section 9.3) 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 IgM+ for Hepatitis core antigen will not be eligible
for trial enrollment

19. 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 and
have liver function tests that conform to Section 9.3

Exclusion Criteria:

1. Patients with prior anthracycline therapy will be excluded

2. 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

3. 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

4. Prior malignancy within 5 years of enrolment 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)

5. Grade 2 or greater peripheral neuropathy

6. E


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

HIV-associated Hodgkin Lymphoma

Stage III Adult Hodgkin Lymphoma

HIV Infection

Stage IV Adult Hodgkin Lymphoma

Intervention(s)

Drug: Vinblastine

Drug: brentuximab vedotin

Drug: Doxorubicin Hydrochloride

Drug: Dacarbazine

Primary Outcome(s)

Progression-free survival for patients using brentuximab vedotin plus AVD regimen with HIV-associated advanced stage Hodgkin lymphoma (Phase II) [Time Frame: 2 years]

Secondary Outcome(s)

Overall survival [Time Frame: 2 years]

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]

CD8 counts [Time Frame: Up to 1 year]

Partial response rate [Time Frame: 2 years]

Incidence of neurotoxicity in combination with HAART and AVD and brentuximab vedotin [Time Frame: Up to 5 years]

Complete response rate [Time Frame: 2 years]

Complete response rate [Time Frame: 5 years]

Incidence of adverse events of AVD and brentuximab vedotin with HAART [Time Frame: Up to 5 years]

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]

Overall survival [Time Frame: 5 years]

Partial response rate [Time Frame: 5 years]

Prognostic value of FDG-PET in patient with HIV and HL with respect to 2 year progression free survival [Time Frame: baseline]

CD4 counts [Time Frame: Up to 1 year]

Event-free survival [Time Frame: 2 years]

Event-free survival [Time Frame: 5 years]

HAART status [Time Frame: Baseline]

Viral load [Time Frame: Up to 1 year]

Secondary ID(s)

AMC-085

Source(s) of Monetary Support

Please refer to primary and secondary sponsors