PET-Directed Therapy With Pembrolizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Classical Hodgkin Lymphoma
Phase II Study of PET-Directed Frontline Therapy With Pembrolizumab and AVD for Patients With Classical Hodgkin Lymphoma
4 other identifiers
interventional
30
1 country
4
Brief Summary
The purpose of this research study is to evaluate a new drug pembrolizumab in combination with chemotherapy, for the treatment of newly diagnosed Hodgkin lymphoma. The chemotherapy regimen is called AVD and includes three drugs: adriamycin, vinblastin, dacarbazine. Pembrolizumab is currently FDA approved for the treatment of some patients with melanoma, lung cancer and head and neck cancer, but has not yet been approved for the treatment of Hodgkins Lymphoma. The AVD regimen of chemotherapy is currently FDA approved for the treatment of newly diagnosed Hodgkin lymphoma, but has not yet been investigated in combination with pembrolizumab for this disease. For patients who have a new diagnosis of Hodgkins Lymphoma, multi-agent chemotherapy is recommended. Also, for patients who do not have a complete response to chemotherapy (meaning there is still evidence of disease on PET scans performed at the end of treatment), radiation is sometimes recommended. Furthermore, the rare patient who relapses after chemotherapy requires treatment with high dose chemotherapy and a transplant.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Nov 2017
Longer than P75 for phase_2
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 19, 2017
CompletedFirst Posted
Study publicly available on registry
July 21, 2017
CompletedStudy Start
First participant enrolled
November 9, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 17, 2019
CompletedResults Posted
Study results publicly available
July 15, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2024
CompletedJune 2, 2023
May 1, 2023
1.5 years
July 19, 2017
May 14, 2020
May 31, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Complete Response (CR) With Pembrolizumab Treatment Alone
To assess the primary objective of response rate following PET #2 performed after 3 doses of pembrolizumab. PET response will be assessed using the Lugano Criteria (2014) which recommends the 5 point Deauville score for assessing response. The Deauville five-point scale is an internationally-recommended scale for routine clinical reporting and clinical trials using FDG PET-CT in the initial staging and assessment of treatment response in Hodgkin lymphoma (HL). Patients with a Deauville score of 1-3 will be considered a complete response. Deauville criteria is defined as follows: 1. No residual uptake 2. Slight uptake, but below blood pool (mediastinum) 3. Uptake above mediastinum, but below or equal to uptake in the liver 4. Uptake slightly to moderately higher than liver 5. Markedly increased uptake or any new lesions Patients will be evaluable for response assessment if they have received at least one dose of pembrolizumab.
After 3 cycles of pembrolizumab (1 cycle = 21 days)
Secondary Outcomes (6)
Incidence of Adverse Events
Up to 2 years
Progression Free Survival (PFS) for Patients <60
Up to 2 years
PFS for Elderly Patients
Up to 2 years
Overall Survival (OS) for Patients <60
Up to 2 years
OS for Elderly Patients
Up to 2 years
- +1 more secondary outcomes
Study Arms (1)
Treatment (FDG-PET/CT, pembrolizumab, chemotherapy)
EXPERIMENTALSee Detailed Description
Interventions
Undergo FDG-PET/CT
Given IV
Given IV
Undergo FDG-PET/CT
Correlative studies
Given IV
Undergo FDG-PET/CT
Given IV
Eligibility Criteria
You may qualify if:
- Patients must have a histologically confirmed diagnosis of classical Hodgkin lymphoma including nodular sclerosis, mixed cellularity, lymphocytic-rich, and lymphocyte depleted subtypes by the 4th edition of the World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues published in 2008 (nodular lymphocyte-predominant Hodgkin lymphoma \[NLPHL\] excluded)
- Patients must have measurable disease by the Lugano criteria
- Patients must have previously untreated disease (except for one week or less of corticosteroids)
- Patients must exhibit a/an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Patients may have any stage and any International Prognostic Score (IPS)
- Patients must have adequate organ and bone marrow function within 14 days prior to registration, as defined below:
- Leukocytes \>= 3,000/mcL
- Absolute neutrophil count \>= 1,500/mcL
- Platelets \>= 100,000/mcl
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X institutional upper limit of normal (ULN)
- Creatinine within normal institutional limits
- Platelet transfusions are acceptable prior to treatment to achieve the above numbers, however growth factors are not allowed within 14 days of registration
- Females of child-bearing potential (FOCBP) and males must agree to avoid becoming pregnant, or impregnating a partner, respectively, by complying with any of the approved contraception techniques prior to registration, for the duration of study participation, and for 120 days following completion of therapy; abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject; should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- +4 more criteria
You may not qualify if:
- Patients are not eligible who have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to registration or who have not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent
- NOTE: Subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study
- NOTE: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
- Patients who have a diagnosis of immunodeficiency or are receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to registration are not eligible
- Patients who have a known history of active TB (bacillus tuberculosis) are not eligible
- Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab
- Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Patients who have a known additional malignancy that is progressing or requires active treatment are not eligible
- NOTE: Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
- Patients who have known active central nervous system (CNS) metastases and/or carcinomatous meningitis are not eligible
- NOTE: Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to registration; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
- Patients who have active autoimmune disease that has required systemic treatment in the past 2 years are not eligible (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Northwestern Universitylead
- National Cancer Institute (NCI)collaborator
- Merck Sharp & Dohme LLCcollaborator
Study Sites (4)
Stanford Cancer Institute
Stanford, California, 94305, United States
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322, United States
Northwestern University
Chicago, Illinois, 60611, United States
Rutgers Cancer Institute
New Brunswick, New Jersey, 08903, United States
Related Publications (3)
Kreuzberger N, Goldkuhle M, von Tresckow B, Kobe C, Sickinger MT, Monsef I, Skoetz N. Positron emission tomography-adapted therapy for first-line treatment in adults with Hodgkin lymphoma. Cochrane Database Syst Rev. 2025 Mar 26;3(3):CD010533. doi: 10.1002/14651858.CD010533.pub3.
PMID: 40135712DERIVEDAllen PB, Lu X, Chen Q, O'Shea K, Chmiel JS, Slonim LB, Sukhanova M, Savas H, Evens AM, Advani R, Pro B, Karmali R, Palmer B, Bayer RA, Eisner RM, Mou E, Dillehay G, Gordon LI, Winter JN. Sequential pembrolizumab and AVD are highly effective at any PD-L1 expression level in untreated Hodgkin lymphoma. Blood Adv. 2023 Jun 27;7(12):2670-2676. doi: 10.1182/bloodadvances.2022008116.
PMID: 36083129DERIVEDAllen PB, Savas H, Evens AM, Advani RH, Palmer B, Pro B, Karmali R, Mou E, Bearden J, Dillehay G, Bayer RA, Eisner RM, Chmiel JS, O'Shea K, Gordon LI, Winter JN. Pembrolizumab followed by AVD in untreated early unfavorable and advanced-stage classical Hodgkin lymphoma. Blood. 2021 Mar 11;137(10):1318-1326. doi: 10.1182/blood.2020007400.
PMID: 32992341DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Jane N. Winter, M.D.
- Organization
- Northwestern University, Feinberg School of Medicine
Study Officials
- PRINCIPAL INVESTIGATOR
Jane Winter, M.D.
Northwestern University
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
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
July 19, 2017
First Posted
July 21, 2017
Study Start
November 9, 2017
Primary Completion
May 17, 2019
Study Completion
October 1, 2024
Last Updated
June 2, 2023
Results First Posted
July 15, 2020
Record last verified: 2023-05