Trial Title:
PET Adapted Brentuximab Vedotin and Pembrolizumab in Combination With Doxorubicin and Dacarbazine in Classic Hodgkin Lymphoma
NCT ID:
NCT05922904
Condition:
Hodgkin Lymphoma
Conditions: Official terms:
Lymphoma
Hodgkin Disease
Pembrolizumab
Brentuximab Vedotin
Doxorubicin
Liposomal doxorubicin
Dacarbazine
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Brentuximab vedotin
Description:
Given by IV (vein)
Arm group label:
Part A: Pembrolizumab and Brentuximab +AD
Arm group label:
Part B: De-Escalation
Arm group label:
Part C: Standard Risk Arm
Intervention type:
Drug
Intervention name:
Doxorubicin Hydrochloride
Description:
Given by IV (vein)
Arm group label:
Part A: Pembrolizumab and Brentuximab +AD
Arm group label:
Part B: De-Escalation
Arm group label:
Part C: Standard Risk Arm
Other name:
Adriamycin PFS®
Other name:
Adriamycin RDF™
Other name:
Adriamycin®
Other name:
Rubex®
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
Given by IV (vein)
Arm group label:
Part A: Pembrolizumab and Brentuximab +AD
Arm group label:
Part B: De-Escalation
Arm group label:
Part C: Standard Risk Arm
Other name:
SGN-35
Other name:
Adcetris
Intervention type:
Drug
Intervention name:
Dacarbazine
Description:
Given by IV (vein)
Arm group label:
Part A: Pembrolizumab and Brentuximab +AD
Arm group label:
Part B: De-Escalation
Arm group label:
Part C: Standard Risk Arm
Other name:
DTIC-Dome®
Summary:
To learn about the effects of brentuximab vedotin and pembrolizumab in combination with
doxorubicin and dacarbazine when given to patients who have Stage II cHL with bulky
mediastinal disease or advanced cHL (Stage III or IV) and who have not received treatment
for the disease.
Detailed description:
Primary Objectives:
● To assess the complete response (CR) rate at the end of therapy (EOT) with Brentuximab
vedotin and pembrolizumab, doxorubicin and dacarbazine in subject with previously
untreated stage II bulky mediastinal disease or advanced stage cHL.
Secondary Objectives:
- To assess the safety of BvP+AD
- To assess the complete remission rate at interim PET (CR iPET)
- To assess the overall response rate (ORR)
- To assess the duration of response (DOR)
- To assess the duration of complete response (DOCR)
- To assess event-free survival (EFS)
- To assess progression free survival (PFS)
- To assess overall survival (OS)
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Treatment-naïve, HL subjects with Ann Arbor stage III, IV, or stage II with bulky
disease (>10 cm).
2. Histologically confirmed cHL according to the current World Health Organization
Classification (nodular sclerosis, mixed cellularity, lymphocyte rich, lymphocyte
depleted, classical HL, or not otherwise specified). a. Subjects enrolling must
submit a tumor block for analysis. Availability of tissue must be confirmed prior to
enrollment.
3. Bidimensional measurable disease as documented by PET/CT or CT imaging. Must have at
least one lesion >15 mm (1.5 cm) in the longest diameter on cross-sectional imaging,
measurable in 2 perpendicular dimensions on CT (or MRI), and FDG avid by PET.
4. Age 18 years or older.
5. An Eastern Cooperative Oncology Group (ECOG) performance status zero, or one.
6. Subjects of childbearing potential must have a negative serum or urine beta human
chorionic gonadotropin (β-hCG) pregnancy test result within 7 days prior to the
first dose of brentuximab vedotin. Subjects with false positive results and
documented verification that the subject is not pregnant are eligible for
participation. Subjects of non-childbearing potential are those who are
postmenopausal >1 year or who have had a bilateral oophorectomy or hysterectomy.
7. If sexually active in a way that could result in pregnancy, subjects of childbearing
potential must agree to use 2 effective contraception methods during the study and
for 7 months following the last dose of study drug. Subjects who can father children
and have partners of childbearing potential must agree to use 2 effective
contraception methods during the study and for 7 months following the last dose of
study drug. Subjects who can father children must also be willing to refrain from
sperm donation during this time.
8. The subject or the subject's legally acceptable representative must provide written
informed consent. Cognitive ability will be assessed according to policy CLN0547.
9. The following baseline laboratory data:
- absolute neutrophil count ≥1500/μL unless there is known HL marrow involvement
- platelet count ≥75,000/μL
- serum bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN for subjects
with Gilbert's disease
- estimated glomerular filtration rate (GFR) ≥30 mL/min/1.73 m2 using the
Modification of Diet in Renal Disease (MDRD) study equation as applicable
- alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x ULN or
≤5 x ULN if there is documented hepatic involvement of HL
- hemoglobin ≥8 g/dL
Exclusion Criteria:
1. Nodular lymphocyte predominant HL.
2. History of another malignancy within 3 years before the first dose of study drug or
any evidence of residual disease from a previously diagnosed malignancy. Exceptions
are malignancies with a negligible risk of metastasis or death (e.g., 5-year OS
≥90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin
carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine
cancer. Subjects with nonmelanoma skin cancer, localized prostate cancer, or
carcinoma in situ of any type are not excluded if they have undergone complete
resection.
3. Prior immunosuppressive chemotherapy, therapeutic radiation, or any immunotherapy
(e.g., immunoglobulin replacement, other monoclonal antibody therapies) within 4
weeks of first study drug dose, unless underlying disease has progressed on
treatment.
4. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody,
or any other antibody or drug specifically targeting T-cell co-stimulation or
checkpoint pathways.
5. Active cerebral/meningeal disease related to the underlying malignancy, including
signs or symptoms of progressive multifocal leukoencephalopathy (PML) or history of
PML. Subjects with a history of cerebral/meningeal disease related to the underlying
malignancy are allowed if prior CNS disease has been treated.
6. Any active Grade 3 or higher (per the National Cancer Institute's Common Terminology
Criteria for Adverse Events [NCI CTCAE] Version 4.03) viral, bacterial, or fungal
infection within 1 week prior to the first dose of study drug. Routine antimicrobial
prophylaxis is permitted.
7. Current therapy with other systemic anti-neoplastic or investigational agents.
8. Planned consolidative radiotherapy.
9. Active interstitial lung disease that is symptomatic or may interfere with the
detection or management of suspected drug-related pulmonary toxicity.
10. Grade 3 or higher pulmonary disease unrelated to underlying malignancy.
11. Idiopathic interstitial pneumonia or diffusing capacity of the lung for carbon
monoxide (adjusted for hemoglobin) <50% predicted.
12. Documented history of a cerebral vascular event (stroke or transient ischemic
attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with
New York Heart Association Class III-IV within 6 months prior to their first dose of
brentuximab vedotin. See Appendix E
13. Subjects with Child-Pugh class B or C hepatic impairment.
14. Other serious underlying medical condition that, in the opinion of the investigator,
would impair the subject's ability to receive or tolerate the planned treatment and
follow-up.
15. Symptomatic neurologic disease compromising normal activities of daily living or
requiring medications. See Appendix G
16. Grade 2 or higher peripheral sensory or motor neuropathy at baseline.
17. Left ventricular ejection fraction <45% or symptomatic cardiac disease (including
symptomatic ventricular dysfunction, symptomatic coronary artery disease, and
symptomatic arrhythmias), or previous treatment with complete cumulative doses of
doxorubicin or other anthracyclines.
18. Subjects with acute or chronic graft-versus-host-disease (GvHD) or receiving
immunosuppressive therapy as treatment for or prophylaxis agent against GvHD.
19. Previous treatment with brentuximab vedotin.
20. Known history of hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
detected) infection.
21. Known to be positive for human immunodeficiency virus (HIV).
22. Subjects who are pregnant or breastfeeding.
23. Known hypersensitivity to any excipient contained in the drug formulation of
brentuximab vedotin, any component of AD, pembrolizumab, doxorubicin, dacarbazine,
filgrastim, or pegfilgrastim.
24. Treatment with botanical preparations (e.g., herbal supplements, traditional Chinese
medicines) intended to treat the disease under study within 2 weeks prior to
treatment.
25. Subjects who have received a live or attenuated vaccine within 30 days prior to
treatment.
26. Subjects with an active autoimmune disease or any other condition requiring systemic
treatment with either corticosteroids within 7 days (>10 mg daily prednisone
equivalent) or other immunosuppressive medications within 30 days of starting
treatment. Inhaled or topical steroids, and adrenal replacement steroid doses >10 mg
daily prednisone equivalent, are permitted in the absence of active autoimmune
disease. a. Subjects with type I diabetes mellitus, hypothyroidism only requiring
hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not
requiring systemic treatment, or conditions not expected to recur in the absence of
an external trigger are permitted to enroll.
27. Subjects who received organ transplant or allogeneic stem cell transplantation.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
M D Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Hun Lee, MD
Phone:
713-794-1829
Email:
hunlee@mdanderson.org
Investigator:
Last name:
Hun Lee, MD
Email:
Principal Investigator
Start date:
December 14, 2023
Completion date:
October 30, 2025
Lead sponsor:
Agency:
M.D. Anderson Cancer Center
Agency class:
Other
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Collaborator:
Agency:
Seagen Inc.
Agency class:
Industry
Source:
M.D. Anderson Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05922904
http://www.mdanderson.org
