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Classical Hodgkin LymphomaPhase 2NCT03226249

PET-Directed Therapy With Pembrolizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Classical Hodgkin Lymphoma

A Phase 2 study testing Computed Tomography, Dacarbazine and Doxorubicin Hydrochloride in people with Classical Hodgkin Lymphoma and Lymphocyte-Depleted Classical Hodgkin Lymphoma, run by Northwestern University at 4 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Computed Tomography, Dacarbazine and Doxorubicin Hydrochloride
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
4 sitesUnited States
Study dates
9 Nov 2017to Oct 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Winship Cancer Institute of Emory University

    Atlanta, Georgia, 30322

  • Northwestern University

    Chicago, Illinois, 60611

  • Rutgers Cancer Institute

    New Brunswick, New Jersey, 08903

  • Stanford Cancer Institute

    Stanford, California, 94305

Other trials in United States

About this study

Official title: Phase II Study of PET-Directed Frontline Therapy With Pembrolizumab and AVD for Patients With Classical Hodgkin Lymphoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

  1. 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.

Being tested
Computed Tomography, Dacarbazine, Doxorubicin Hydrochloride, Fludeoxyglucose F-18, Laboratory Biomarker Analysis
Medical subject headings
Hodgkin Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computerized Axial Tomography, computerized tomography

    Undergo FDG-PET/CT

  • DacarbazineDrug

    Also called 4-(Dimethyltriazeno)imidazole-5-carboxamide, 5-(Dimethyltriazeno)imidazole-4-carboxamide, Asercit, Biocarbazine

    Given IV

  • Doxorubicin HydrochlorideDrug

    Also called 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin

    Given IV

  • Fludeoxyglucose F-18Radiation

    Also called 18FDG, FDG, fludeoxyglucose F 18, Fludeoxyglucose F18

    Undergo FDG-PET/CT

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan

    Undergo FDG-PET/CT

  • Vinblastine SulfateDrug

    Also called 29060 LE, 29060-LE, Exal, Velban

    Given IV

Study groups in NCT03226249
Study groupRoleWhat they receive
Treatment (FDG-PET/CT, pembrolizumab, chemotherapy)ExperimentalSee Detailed Description
Receives: Procedure: Computed Tomography; Drug: Dacarbazine; Drug: Doxorubicin Hydrochloride; Radiation: Fludeoxyglucose F-18; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Procedure: Positron Emission Tomography; Drug: Vinblastine Sulfate

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: After 3 cycles of pembrolizumab (1 cycle = 21 days)

Secondary outcomes (6)

  1. Incidence of Adverse Events

    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).

    Measured: Up to 2 years

  2. Progression Free Survival (PFS) for Patients <60

    PFS for patients <60 will be measured.

    Measured: Up to 2 years

  3. PFS for Elderly Patients

    PFS for elderly patients will be measured.

    Measured: Up to 2 years

  4. Overall Survival (OS) for Patients <60

    OS for patients <60 will be evaluated.

    Measured: Up to 2 years

  5. OS for Elderly Patients

    OS for elderly patients will be evaluated.

    Measured: Up to 2 years

  6. FDG Uptake

    Evaluate the extent of FDG uptake by assessing PET scans to determine a Deauville score.

    Measured: Up to 4 weeks after last dose of chemotherapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jul 2017
  2. Study start9 Nov 2017
  3. Primary completion17 May 2019
  4. Study completionOct 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03226249
Sponsor's protocol ID
NU 16H08
Other IDs
NU 16H08, P30CA060553, NCI-2017-00457, STU00203707
Status last verified
May 2023
First submitted
19 Jul 2017
Last updated
2 Jun 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 40135712

  • Allen 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.

    PubMed 36083129

  • Allen 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.

    PubMed 32992341

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Computed Tomography, Dacarbazine and Doxorubicin Hydrochloride in people with Classical Hodgkin Lymphoma and Lymphocyte-Depleted Classical Hodgkin Lymphoma, run by Northwestern University at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 2 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete Response (CR) With Pembrolizumab Treatment Alone (time frame: After 3 cycles of pembrolizumab (1 cycle = 21 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03226249, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2023.

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