A Phase II Trial of Ipilimumab With and Without Nivolumab in Patients With Relapsed/Refractory Classic Hodgkin Lymphoma
Overview
- Phase
- Phase 2
- Intervention
- Nivolumab
- Conditions
- Hodgkin Lymphoma
- Sponsor
- Dana-Farber Cancer Institute
- Enrollment
- 13
- Locations
- 4
- Primary Endpoint
- Overall Response Rate (ORR)
- Status
- Active, not recruiting
- Last Updated
- 2 months ago
Overview
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
Detailed Description
This is an open-label, multi-center, phase II study of ipilimumab with or without nivolumab for patients with relapsed or refractory (R/R) classic Hodgkin lymphoma (cHL). Nivolumab is a drug which is approved by the United States Food and Drug Administration (FDA) for the treatment of adult patients experiencing relapsed Hodgkin lymphoma (cHL) who have received at least two prior systemic therapies. Ipilimumab has been approved by the FDA for the treatment of metastatic melanoma (a type of skin cancer), and specific types of previously treated advanced kidney cancers. The study drugs have not been approved in combination for cHL by the Food and Drug Administration (FDA). This study is for participants who previously had progressive disease when receiving a PD-1 mAb. Participants will receive 4 cycles of ipilimumab monotherapy and then undergo restaging imaging. Patients who achieved an objective response will continue treatment with ipilimumab maintenance. Other patients will receive 4 cycles of nivolumab and ipilimumab followed by ipilimumab maintenance treatment. Patients who have progressive disease after fewer than 4 cycles of ipilimumab are eligible to proceed to combination therapy with nivolumab and ipilimumab if they are clinically stable. Participants will receive up to \~ 24 months of study treatment. After completion of therapy, participants will be followed every 3 months for 2 years and then every 6 months for the next 5 years. It is expected that about 13 people will participate in this research study. Bristol Myers Squibb (BMS) is supporting this research study by providing the study drugs and funding for the study.
Investigators
Reid Merryman, MD
Principal Investigator
Dana-Farber Cancer Institute
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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).
Arms & Interventions
Disease Progression after previous therapy
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
Intervention: Nivolumab
Disease Progression after previous therapy
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
Intervention: Ipilimumab
Outcomes
Primary Outcomes
Overall Response Rate (ORR)
Time Frame: From enrollment to completion of 4 cycles (each cycle is 21 days) of treatment
Patients achieving a complete (CR) or partial response (PR), assessed by PET/CT (using Lugano)
Secondary Outcomes
- 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)
- Overall Response Rate (ORR) Ipilimumab and Nivolumab Combination Therapy, LYRIC(24 weeks)
- Progression-free Survival, LYRIC(2 years)
- Duration of Response(2 years)
- Progression-free Survival, Lugano(2 years)
- Overall Survival(2 years)
- Percent of Patients With Grade 3+ Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0(2 years)