Ipilimumab With or Without Nivolumab in Relapsed/Refractory cHL

NCT04938232 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 21-204
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 4

Brief Summary

This study is looking at the effects of Ipilimumab when it is given alone or in combination with Nivolumab to patients with relapsed or refractory classic Hodgkin's lymphoma (cHL). The names of the study drugs involved in this study are:

• Ipilimumab
• Nivolumab

Conditions

Hodgkin Lymphoma; Relapsed Hodgkin's Disease, Adult; Refractory Hodgkin Lymphoma

Keywords

Hodgkin lymphoma; Relapsed Hodgkin's Disease, Adult; Refractory Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Patients achieving a complete (CR) or partial response (PR), assessed by PET/CT (using Lugano)

  From enrollment to completion of 4 cycles (each cycle is 21 days) of treatment

Secondary Outcomes (11)

• Overall Response Rate (ORR) Ipilimumab Monotherapy, Lugano

  12 weeks

• Overall Response Rate (ORR) Ipilimumab Monotherapy, LYRIC

  12 weeks

• Complete Response Rate (CRR) Ipilimumab Monotherapy, Lugano

  12 weeks

• Complete Response Rate (CRR) Ipilimumab Monotherapy, LYRIC

  12 weeks

• Overall Response Rate (ORR) Ipilimumab and Nivolumab Combination Therapy, Lugano

  24 weeks

Study Arms (1)

Disease Progression after previous therapy

EXPERIMENTAL

Participants will receive Ipilimumab alone and depending on response will receive either a maintenance course of Ipilimumab or a course of Nivolumab and Ipilimumab in combination followed by a maintenance course of Ipilimumab. Patients who have progressive disease after fewer than 4 cycles of ipilimumab are also eligible to proceed to combination therapy with nivolumab and ipilimumab, if they are clinically stable. * Ipilimumab Monotherapy: Every 3 weeks for 4 study cycles * Complete Response/Partial Response: Maintenance Ipilimumab every 12 weeks for 8 cycles * Stable or Progressive Disease Response: Nivolumab and Ipilimumab every 3 weeks for 4 study cycles, followed by Maintenance Ipilimumab every 12 weeks for 7 cycles

Drug: Nivolumab; Drug: Ipilimumab

Interventions

Nivolumab DRUG

Intravenous infusion

Also known as: Opdivo

Disease Progression after previous therapy

Ipilimumab DRUG

Intravenous infusion

Also known as: Yervoy

Disease Progression after previous therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically determined classic Hodgkin lymphoma with pathologic review at the participating institution.
• Participants must have measurable disease, defined as a lymph node or tumor mass ≥1.5 cm in at least one dimension by CT, PET/CT, or MR. Imaging must have been completed no greater than 6 weeks prior to study enrollment. Measurable disease that has previously been irradiated is permissible only if there has been evidence of progression since the radiation.
• Patients must have progressed after two or more lines of systemic treatment, including autologous stem cell transplantation, if eligible.
• Progression of disease or relapse following treatment with nivolumab or pembrolizumab. Intervening treatments with between PD-1 mAb therapy and the trial are permitted.
• Patients may have had a prior autologous stem cell transplant and may have been treated with chimeric antigen receptor T-cells (CAR T-cells).
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (see Appendix A)
• Adequate hematologic and organ function as defined below:
• Absolute neutrophil count \> 1.0x109/L unless due to marrow involvement by lymphoma in which case ANC must be \>0.75x109/L. Growth factor support is allowed provided it is received at least 5 days prior to enrollment labs.
• Platelets \> 75 x109/L, unless due to marrow involvement by lymphoma, in which case platelets must be \>50 x109/L
• Estimated GFR (by Cockroft-Gault equation) \> 40ml/min
• Total bilirubin \< 1.5 X ULN
• AST/ALT \< 2.5 X ULN
• Ability to understand and the willingness to sign a written informed consent document.
• Willingness to provide pre-treatment tumor sample by core needle or excisional surgical biopsy. An archival sample is acceptable in the following situations: the sample was acquired within 90 days of initiation of PD-1 therapy AND the following provisions are met: 1) availability of a tumor-containing formalin fixed, paraffin embedded (FFPE) tissue block, 2) if the tumor containing FFPE tissue block cannot be provided in total, sections from this block should be provided that are freshly cut and mounted on positively charged glass slides (SuperFrost Plus are recommended). Preferably, 25 slides should be provided; if not possible, a minimum of 15 slides is required. Exceptions to this criterion may be made with approval of the Study Chair.

You may not qualify if:

• Patients currently receiving anticancer therapies or who have received anticancer therapies within 28 days of the start of study drug (including chemotherapy, radiation therapy, antibody-based therapy, etc.), or 56 days for radioimmunotherapy. Steroids for symptom palliation are allowed but must be either discontinued or on stable doses of \< 10mg daily of prednisone (or the equivalent) at the time of initiation of protocol therapy.
• Patients may not be receiving any other investigational agents or have received investigational agents within 4 weeks (or 3 half-lives, whichever is longer) of beginning treatment.
• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy unless in consultation with an allergy specialist they are deemed eligible for retreatment with desensitization.
• Patients who have undergone prior allogeneic stem cell transplantation
• Patients with a history of or active autoimmune disease (except controlled asthma, Hashimoto thyroiditis, atopic dermatitis, or vitiligo), or requiring systemic corticosteroids at a dose of 10mg prednisone equivalent daily. Patients with a history of autoimmune disease who never required corticosteroids and with no evidence of disease activity, and in whom the risk of reactivation is felt not to be serious, may be enrolled after discussion with the overall study chair. Exceptions to this are patients with a history of inflammatory bowel disease (ulcerative colitis and Crohn's disease). These patients are excluded regardless of whether their disease is active or inactive.
• Patients who experienced grade 4 immune-related adverse events (irAEs) during treatment with a PD-1 mAb.
• Patients with active pneumonitis or colitis, or patients with cirrhosis.
• Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia).
• Patients with known HIV infection or hepatitis B or C infection. Testing for HIV is optional. Testing for hepatitis B and C is mandatory. Patients with hepatitis B core Ab positivity but negative surface antigen and negative viral load may be enrolled if they can be treated with a prophylactic agent (eg, entecavir); patients with hepatitis C seropositivity who have a negative viral load can also be enrolled.
• Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
• Prior history of another malignancy (except for non-melanoma skin cancer or in situ cervical or breast cancer) unless disease free for at least 2 years. Patients with prostate cancer are allowed if PSA is less than 1.
• Patients should not have received immunization with attenuated live vaccine within one week of study entry or during study period.
• History of noncompliance to medical regimens.
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study.
• Patients with any one of the following currently on or in the previous 6 months will be excluded: myocardial infarction, congenital long QT syndrome, torsade de pointes, left anterior hemiblock, unstable angina, coronary/peripheral artery bypass graft, or cerebrovascular accident.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Bristol-Myers Squibb: collaborator

Study Sites (4)

University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Reid Merryman
• Organization: Dana-Farber Cancer Institute

reid_merryman@dfci.harvard.edu

6176326844

Study Officials

• Reid W Merryman, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: June 8, 2021
• First Posted: June 24, 2021
• Study Start: June 4, 2021
• Primary Completion: April 1, 2024
• Study Completion (Estimated): August 1, 2026
• Last Updated: February 5, 2026
• Results First Posted: April 3, 2025

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (4)