- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03226249
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
Study Overview
Status
Conditions
Detailed Description
PRIMARY OBJECTIVES:
I. Assess the percent of patients who achieve a complete response (CR) to single-agent pembrolizumab induction, among patients with classical Hodgkin lymphoma (cHL) using Lugano 2014 criteria., as measured at PET #2.
SECONDARY OBJECTIVES:
I. Assess the safety and tolerability of pembrolizumab in combination with chemotherapy in the frontline setting.
II. Determine the three-year progression free survival (PFS) and overall survival (OS) for patients < 60 with early non-bulky disease, and elderly patients (all stages) treated with pembrolizumab with doxorubicin hydrochloride (Adriamycin), (bleomycin), vinblastine sulfate, dacarbazine (A[B]VD) in the frontline treatment of patients with cHL.
III. Determine the extent of fludeoxyglucose F-18 (FDG) uptake, using a semi-quantitative approach (e.g., Deauville score), after pembrolizumab induction, and after subsequent chemotherapy.
TERTIARY OBJECTIVES:
I. To characterize PD-1 pathway specific expression and correlate with response.
II. To characterize serum biomarkers of immune and inflammatory response during treatment.
III. To characterize levels of soluble PD-L1 related to treatment with pembrolizumab.
IV. To characterize T-lymphocyte subset changes to treatment with pembrolizumab.
V. To investigate the prevalence and clinical correlation of chromosome 9p24.1 alterations for this population.
OUTLINE:
INITIATION: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo FDG-PET/computed tomography (CT) scans before the start of pembrolizumab and after 3 courses.
AVD: Within 21 days after final dose of pembrolizumab, patients receive doxorubicin hydrochloride IV, vinblastine sulfate IV, and dacarbazine IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo a final FDG-PET/CT scan on day 117-120 or 26-29 of course 2. Patients with stage I/II disease with a CR continue treatment for up to 2 courses. Patients with stage III/IV disease with a CR or age >= 60 with stage III/IV disease with any response continue treatment for up to 4 courses.
CONSOLIDATION: Patients age >= 60 with stage III/IV disease who received < 6 courses of AVD or patients age >= 60 with DV 4-5 on FDG-PECT/CT scan receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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California
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Stanford, California, United States, 94305
- Stanford Cancer Institute
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Georgia
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Atlanta, Georgia, United States, 30322
- Winship Cancer Institute of Emory University
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Illinois
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Chicago, Illinois, United States, 60611
- Northwestern University
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New Jersey
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New Brunswick, New Jersey, United States, 08903
- Rutgers Cancer Institute
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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:
- Has not undergone a hysterectomy or bilateral oophorectomy
Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)
- FOCBP must have a negative pregnancy test within 7 days prior to registration on study; NOTE: a negative pregnancy test is also required within 3 days prior to first dose of pembrolizumab and therefore may need to be repeated if screening test is more than 3 days prior to first dose
- Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study
Exclusion Criteria:
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)
- NOTE: Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Patients who have known history of, or any evidence of active, non-infectious pneumonitis are not eligible
- Patients who have an active infection requiring systemic therapy are not eligible, except for uncomplicated urinary tract infections
- Patients are not eligible who have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject?s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
- Patients who have known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial are not eligible
- Patients may not be pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, from registration through 120 days after the last dose of trial treatment
- Patients who have received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent are not eligible
- Patients who have a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) are not eligible
- Patients who have active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis c virus [HCV] ribonucleic acid [RNA] [qualitative] is detected) are not eligible
Patients who received a live vaccine within 30 days of planned start of study therapy are not eligible; examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, bacillus Calmette-Guerin (BCG), and typhoid vaccine
- NOTE: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (FDG-PET/CT, pembrolizumab, chemotherapy)
See Detailed Description
|
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Undergo FDG-PET/CT
Other Names:
Undergo FDG-PET/CT
Other Names:
Undergo FDG-PET/CT
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Complete Response (CR) With Pembrolizumab Treatment Alone
Time Frame: After 3 cycles of pembrolizumab (1 cycle = 21 days)
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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:
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)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Adverse Events
Time Frame: Up to 2 years
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To assess safety and tolerability, all adverse events will be summarized in terms of type, grade, timing and attribution to treatment and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI-CTCAE version 4.03).
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Up to 2 years
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Progression Free Survival (PFS) for Patients <60
Time Frame: Up to 2 years
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PFS for patients <60 will be measured.
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Up to 2 years
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PFS for Elderly Patients
Time Frame: Up to 2 years
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PFS for elderly patients will be measured.
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Up to 2 years
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Overall Survival (OS) for Patients <60
Time Frame: Up to 2 years
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OS for patients <60 will be evaluated.
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Up to 2 years
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OS for Elderly Patients
Time Frame: Up to 2 years
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OS for elderly patients will be evaluated.
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Up to 2 years
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FDG Uptake
Time Frame: Up to 4 weeks after last dose of chemotherapy
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Evaluate the extent of FDG uptake by assessing PET scans to determine a Deauville score.
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Up to 4 weeks after last dose of chemotherapy
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Jane Winter, M.D., Northwestern University
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma
- Hodgkin Disease
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antineoplastic Agents, Immunological
- Radiopharmaceuticals
- Antibiotics, Antineoplastic
- Immune Checkpoint Inhibitors
- Fluorodeoxyglucose F18
- Pembrolizumab
- Doxorubicin
- Liposomal doxorubicin
- Dacarbazine
- Vinblastine
- Imidazole
- Deoxyglucose
Other Study ID Numbers
- NU 16H08 (Other Identifier: Northwestern University)
- P30CA060553 (U.S. NIH Grant/Contract)
- NCI-2017-00457 (Other Identifier: CTRP (Clinical Trial Reporting Program))
- STU00203707 (Other Identifier: Northwestern University IRB#)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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