Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03226249
Recruitment Status : Active, not recruiting
First Posted : July 21, 2017
Last Update Posted : March 14, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Northwestern University

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 Hodgkin 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 Hodgkn?s 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.

Condition or disease Intervention/treatment Phase
Classical Hodgkin Lymphoma Lymphocyte-Depleted Classical Hodgkin Lymphoma Lymphocyte-Rich Classical Hodgkin Lymphoma Mixed Cellularity Classical Hodgkin Lymphoma Nodular Sclerosis Classical Hodgkin Lymphoma 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 Phase 2

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of PET-Directed Frontline Therapy With Pembrolizumab and AVD for Patients With Classical Hodgkin Lymphoma
Actual Study Start Date : September 6, 2017
Estimated Primary Completion Date : August 1, 2020
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment (FDG-PET/CT, pembrolizumab, chemotherapy)
See Detailed Description
Procedure: Computed Tomography
Undergo FDG-PET/CT
Other Names:
  • CAT
  • CAT Scan
  • Computerized Axial Tomography
  • computerized tomography
  • CT
  • CT SCAN
  • tomography

Drug: Dacarbazine
Given IV
Other Names:
  • 4-(Dimethyltriazeno)imidazole-5-carboxamide
  • 5-(Dimethyltriazeno)imidazole-4-carboxamide
  • Asercit
  • Biocarbazine
  • Dacarbazina
  • Dacarbazina Almirall
  • Dacarbazine - DTIC
  • Dacatic
  • Dakarbazin
  • Deticene
  • Detimedac
  • DIC
  • Dimethyl (triazeno) imidazolecarboxamide
  • Dimethyl Triazeno Imidazol Carboxamide
  • Dimethyl Triazeno Imidazole Carboxamide
  • dimethyl-triazeno-imidazole carboxamide
  • Dimethyl-triazeno-imidazole-carboximide
  • DTIC
  • DTIC-Dome
  • Fauldetic
  • Imidazole Carboxamide
  • Imidazole Carboxamide Dimethyltriazeno
  • WR-139007

Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • 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
  • Adriamycin Hydrochloride
  • Adriamycin PFS
  • Adriamycin RDF
  • ADRIAMYCIN, HYDROCHLORIDE
  • Adriamycine
  • Adriblastina
  • Adriblastine
  • Adrimedac
  • Chloridrato de Doxorrubicina
  • DOX
  • DOXO-CELL
  • Doxolem
  • Doxorubicin.HCl
  • Doxorubin
  • Farmiblastina
  • FI 106
  • FI-106
  • hydroxydaunorubicin
  • Rubex

Radiation: Fludeoxyglucose F-18
Undergo FDG-PET/CT
Other Names:
  • 18FDG
  • FDG
  • fludeoxyglucose F 18
  • Fludeoxyglucose F18
  • Fluorine-18 2-Fluoro-2-deoxy-D-Glucose
  • Fluorodeoxyglucose F18

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475

Procedure: Positron Emission Tomography
Undergo FDG-PET/CT
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging

Drug: Vinblastine Sulfate
Given IV
Other Names:
  • 29060 LE
  • 29060-LE
  • Exal
  • Velban
  • Velbe
  • Velsar
  • VINCALEUKOBLASTINE




Primary Outcome Measures :
  1. Complete Response (CR) with pembrolizumab treatment alone [ Time Frame: At 10 weeks ]
    Assess the percent of patients who achieve a CR to single-agent pembrolizumab induction using Lugano 2014 criteria, as measured at PET#2.


Secondary Outcome Measures :
  1. Incidence of Adverse Events [ Time Frame: Up to 2 years ]
    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).

  2. Progression Free Survival (PFS) for patients <60 [ Time Frame: Up to 2 years ]
    PFS for patients <60 will be measured.

  3. PFS for elderly patients [ Time Frame: Up to 2 years ]
    PFS for elderly patients will be measured.

  4. Overall Survival (OS) for patients <60 [ Time Frame: Up to 2 years ]
    OS for patients <60 will be evaluated.

  5. OS for elderly patients [ Time Frame: Up to 2 years ]
    OS for elderly patients will be evaluated.

  6. FDG uptake [ Time Frame: Up to 4 weeks after last dose of chemotherapy ]
    Evaluate the extent of FDG uptake by assessing PET scans to determine a Deauville score.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03226249


Locations
Layout table for location information
United States, California
Stanford Cancer Institute
Stanford, California, United States, 94305
United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, New Jersey
Rutgers Cancer Institute
New Brunswick, New Jersey, United States, 08903
Sponsors and Collaborators
Northwestern University
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Jane Winter, M.D. Northwestern University

Layout table for additonal information
Responsible Party: Northwestern University
ClinicalTrials.gov Identifier: NCT03226249     History of Changes
Other Study ID Numbers: NU 16H08
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# )
First Posted: July 21, 2017    Key Record Dates
Last Update Posted: March 14, 2019
Last Verified: March 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Doxorubicin
Liposomal doxorubicin
Pembrolizumab
Vinblastine
Dacarbazine
Imidazole
Fluorodeoxyglucose F18
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Radiopharmaceuticals
Antineoplastic Agents, Alkylating
Alkylating Agents