ClinicalTrials.gov
ClinicalTrials.gov Menu

A(B)VD Followed by Nivolumab as Frontline Therapy for Higher Risk Patients With Classical Hodgkin Lymphoma (HL)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03033914
Recruitment Status : Recruiting
First Posted : January 27, 2017
Last Update Posted : April 24, 2018
Sponsor:
Collaborators:
Bristol-Myers Squibb
M.D. Anderson Cancer Center
City of Hope Medical Center
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:
The aim of this study is to improve the chance of cure for people with higher risk Hodgkin lymphoma. The purpose of the Phase I study is to test any good and bad effects of the study drug called Nivolumab when combined with ABVD for the front-line treatment of HL.The purpose of this Phase II study is to test whether including nivolumab in treatment for untreated Hodgkin lymphoma can improve the chance of cure for patients with abnormal PET scans after 2 cycles of ABVD.

Condition or disease Intervention/treatment Phase
Hodgkin Lymphoma Drug: doxorubicin Drug: Bleomycin Drug: vinblastine Drug: dacarbazine Drug: Nivolumab Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 26 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Cohort A will include patients less than 60 years of age with advanced stage (Stage III or IV) classical Hodgkin lymphoma (HL) who are at higer risk for relapse due to baseline international prognostic score (IPS) of 3-7 or positive PET scan after 2 cycles of ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) ("PET-2 positive").
Masking: None (Open Label)
Masking Description: Cohort B will include patients 60 years of age and older with HL (any stage). AVD (adriamycin,vinblastine, dacarbazine)
Primary Purpose: Treatment
Official Title: Phase I/II of Nivolumab and A(B)VD in the Front-line Setting for High Risk Hodgkin Lymphoma
Actual Study Start Date : January 25, 2017
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: < 60 years of age with advanced stage (HL) untreated
The study will employ a 3+3 design and include 3 treatment cohorts. In each cohort, patients will receive 6 cycles of A(B)VD and 8 doses of nivolumab. In dose level 1, patients will receive nivolumab in combination with AVD during cycle 6 only followed by 6 additional doses of nivolumab. In subsequent dose levels, nivolumab will be combined with increasing numbers of cycles of AVD. Based upon safety data from another study with Nivolumab, we will no longer need to evaluate dose level 2. If we determine that dose level 1 is safe, the next group of patients will enroll onto dose level 3. A PET scan will be performed after 2 cycles of ABVD and those with a PET-negative response (defined by Deauville 1, 2 or 3) will proceed with 4 additional cycles of ABVD or AVD (per treating physician preference).
Drug: doxorubicin
Doxorubicin: 25 mg/m^2 will be administered by IV infusion on Days 1 and 15 of each 28-day cycle

Drug: Bleomycin
Bleomycin: 10 units/m^2 will be administered by IV infusion on Days 1 and 15 of each 28-day cycle

Drug: vinblastine
Vinblastine: 6 mg/m^2 will be administered by IV infusion on Days 1 and 15 of each 28-day cycle

Drug: dacarbazine
Dacarbazine (DTIC): 375 mg/m^2 will be administered by IV infusion on Days 1 and 15 of each 28-day cycle.

Drug: Nivolumab
nivolumab 240mg q14 days

Experimental: 60 years of age and older with HL (any stage) untreated
The study will employ a 3+3 design and include 3 treatment cohorts. In each cohort, patients will receive 6 cycles of AVD and 12 doses of nivolumab. In this cohort, patients will receive nivolumab in combination with AVD during cycles 5 and 6 only, followed by 8 additional doses of nivolumab. In subsequent cohorts, nivolumab will be combined with increasing numbers of cycles of AVD. Based upon safety data from another study with Nivolumab, we will no longer need to evaluate dose level 2. If we determine that dose level 1 is safe, the next group of patients will enroll onto dose level 3.
Drug: doxorubicin
Doxorubicin: 25 mg/m^2 will be administered by IV infusion on Days 1 and 15 of each 28-day cycle

Drug: vinblastine
Vinblastine: 6 mg/m^2 will be administered by IV infusion on Days 1 and 15 of each 28-day cycle

Drug: dacarbazine
Dacarbazine (DTIC): 375 mg/m^2 will be administered by IV infusion on Days 1 and 15 of each 28-day cycle.

Drug: Nivolumab
nivolumab 240mg q14 days




Primary Outcome Measures :
  1. number of patients who have dose limiting toxicity [ Time Frame: 2 years ]
    For this objective, the standard 3+3 scheme will be used. Initially, 3 patients will enroll onto dose level 1. If no patients experience DLT, enrollment will proceed to the next dose level. If 1 DLT is observed, 3 additional patients will enroll onto dose level 1. If 1 or fewer patients out of 6 experience DLT, enrollment will proceed to the next dose level. If 2 or more DLTs are observed at a given dose level, the previous dose will be declared the MTD. Adverse events will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. If CTCAE grading does not exist for an adverse event, the severity of mild, moderate, severe, and life-threatening, corresponding to Grades 1 - 4, will be used.

  2. Phase II- progression free survival [ Time Frame: 2 year ]
    The updated response criteria entitled "The Lugano Classification" system will be applied to define complete response, partial response, and progression of disease in this study.



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.


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

Inclusion Criteria:

  • Cohort A overview: Patients age less than 60 with untreated stage III or IV classical Hodgkin lymphoma will be eligible for cohort A. In phase I, patients could enroll onto cohort A if they had have a baseline IPS ≥3 OR if their PET scan after 2 cycles of ABVD is positive (Deauville 4 or 5). Enrollment onto phase I has now ceased and enrollment will begin for phase II. In phase II, patients less than 60 years of age with stage III or IV HL are eligible. Patients may enroll anytime within the first 2 cycles of ABVD or after PET-2.
  • Cohort B overview: Patients 60 or older with untreated classical Hodgkin lymphoma (regardless of stage) will be eligible for cohort B.

The following eligibility criteria applies to both cohort A and B except when stated otherwise:

  • Histologic diagnosis of classical Hodgkin lymphoma

    • FDG-avid disease by FDG-PET/CT
    • Ann Arbor Stage III or IV disease (Cohort A only)
    • WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug. Women who undergo fertility preservation within 2 weeks of beginning chemotherapy are expected to have false-positive pregnancy tests and therefore testing may be waived for these patients.
    • WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug. Women who undergo fertility preservation within 2 weeks of beginning chemotherapy are expected to have false-positive pregnancy tests and therefore testing may be waived for these patients.
    • Women must not be breastfeeding
  • Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug plus 5 half-lives of study drug plus 90 days (duration of sperm turnover) for a total of 31 weeks posttreatment completion
  • Age ≥ 18
  • Serum creatinine ≤ 1.5 x Upper limit of normal (ULN) or creatinine clearance (CrCl) ≥ 40 mL/min (measured using the Cockcroft-Gault formula
  • AST/ALT ≤ 3 x ULN (5x ULN for those with lymphoma involvement of the liver)
  • Total bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)

Exclusion Criteria:

  • Subjects with active brain metastases or leptomeningeal metastases.
  • Subjects with nodular lymphocyte-predominant HL
  • Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
  • Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
  • Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • Subjects with a condition requiring systemic treatment with systemic corticosteroids (equivalent of >10mg/day of prednisone). Patients may receive steroid therapy up to 10 days prior to starting ABVD to control lymphoma-related symptoms.
  • Any of the following cardiovascular conditions or values within 6 months before the first dose of study drug:

    • A left-ventricular ejection fraction < 50%
    • Myocardial infarction within 2 years of randomization
    • New York Heart Association (NYHA) Class III or IV heart failure
  • Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • Any positive test for hepatitis B virus or hepatitis C virus indicating acute infection.
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • History of severe hypersensitivity reaction to any monoclonal antibody.
  • Adjusted DLCO <60%

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): NCT03033914


Contacts
Contact: Alison Moskowitz, MD 212-639-4839 moskowia@mskcc.org
Contact: Anas Younes, MD 212-639-5059

Locations
United States, New Jersey
Memorial Sloan Kettering Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Alison Moskowitz, MD    212-639-4839      
Memorial Sloan Kettering Monmouth Recruiting
Middletown, New Jersey, United States, 07748
Contact: Allison Moskowitz, MD    212-639-4839      
United States, New York
Memorial Sloan Kettering Commack Recruiting
Commack, New York, United States, 11725
Contact: Alison Moskowitz, MD    212-639-4839      
Memorial Sloan Kettering Westchester Recruiting
Harrison, New York, United States, 10604
Contact: Alison Moskowitz, MD    212-639-4839      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Alison Moskowitz, MD    212-639-4839      
Contact: Anas Younes, MD    212-639-5059      
Principal Investigator: Alison Moskowitz, MD         
Memorial Sloan Kettering Rockville Centre Recruiting
Rockville Centre, New York, United States, 11570
Contact: Alison Moskowtiz, MD    212-639-4839      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Bristol-Myers Squibb
M.D. Anderson Cancer Center
City of Hope Medical Center
Investigators
Principal Investigator: Alison Moskowitz, MD Memorial Sloan Kettering Cancer Center

Additional Information:
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03033914     History of Changes
Other Study ID Numbers: 16-1536
CA209-447 ( Other Identifier: BMS )
First Posted: January 27, 2017    Key Record Dates
Last Update Posted: April 24, 2018
Last Verified: April 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Memorial Sloan Kettering Cancer Center:
Nivolumab
adriamycin
bleomycin
vinblastine
dacarbazine
16-1536

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Doxorubicin
Liposomal doxorubicin
Bleomycin
Nivolumab
Vinblastine
Antibodies, Monoclonal
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators