National Cancer Institute (NCI)
This phase III trial compares chemotherapy versus an immune checkpoint inhibitor drug called pembrolizumab plus chemotherapy in treating patients with classical Hodgkin lymphoma that has come back (relapsed) or that does not respond to treatment (refractory). The usual approach for patients with classical Hodgkin lymphoma is treatment with standard chemotherapy, including drugs that are Food and Drug Administration (FDA)-approved. If this treatment puts a patient into remission, high dose chemotherapy and stem cell transplant may be used to increase the likelihood of a cure. Hodgkin lymphoma is capable of inhibiting the immune system from killing it. Pembrolizumab is a checkpoint inhibitor that may be able to stop this inhibition, allowing the immune system to attack the lymphoma.
Recurrent Classic Hodgkin Lymphoma
Refractory Classic Hodgkin Lymphoma
Autologous Hematopoietic Stem Cell Transplantation
Bendamustine
Brentuximab Vedotin
Carboplatin
Computed Tomography
Etoposide
Gemcitabine
Ifosfamide
Pegylated Liposomal Doxorubicin Hydrochloride
Pembrolizumab
Positron Emission Tomography
Radiation Therapy
Transplant Conditioning
Vinorelbine
Phase 3
PRIMARY OBJECTIVE: I. To assess the 2-year event free survival (EFS) of patients treated with pembrolizumab added to chemotherapy versus chemotherapy alone, in patients with relapsed/refractory (R/R) classical Hodgkin's lymphoma (cHL) who are intended to receive salvage therapy followed by high dose chemotherapy and autologous stem cell transplant (HDT-ASCT). PRIMARY IMAGING OBJECTIVE: I. To assess the diagnostic performance of baseline total metabolic tumor volume (TMTV) in predicting response (complete remission [CR] + partial remission [PR] versus [vs] no response) at pre-transplant/post-salvage for each arm separately and overall. SECONDARY OBJECTIVES: I. To assess the 2-year progression free survival (PFS) and overall survival (OS) in the transplanted population. II. To assess the complete remission (CR) rate to salvage therapy. III. To assess the CR rate post HDT-ASCT. IV. To assess the post HDT-ASCT partial remission (PR) to CR conversion rate. SECONDARY IMAGING OBJECTIVES: I. To assess the % change in TMTV (delta TMTV) from baseline to pre-transplant/post-salvage in predicting response (CR+PR vs no response) at pre-transplant/post-salvage for each arm separately and overall. II. To assess baseline TMTV and delta TMTV in predicting EFS/OS for each arm separately and overall. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: SALVAGE THERAPY: Patients receive 1 of 3 chemotherapy regimens as clinically indicated: 1) ifosfamide intravenously (IV), carboplatin IV, and etoposide IV; 2) gemcitabine IV, vinorelbine IV, and pegylated liposomal doxorubicin IV; or 3) brentuximab vedotin IV and bendamustine IV. Patients then undergo a positron emission tomography (PET)/computed tomography (CT) scan. Patients who achieve a CR or PR proceed to HDT-ASCT. Patients who achieve stable disease (SD) or progressive disease (PD) come off study treatment. HDT-ASCT: Patients undergo ASCT. Patients may also receive a standard preparative chemotherapy regimen as clinically indicated. Patients who achieve PR prior to ASCT may also undergo radiation therapy (RT) as clinically indicated. Patients who went into ASCT with PR also undergo a PET/CT scan 30 days post-transplant. MAINTENANCE THERAPY: Patients may receive brentuximab vedotin IV as clinically indicated. ARM B: SALVAGE THERAPY: Patients receive pembrolizumab IV plus 1 of 3 chemotherapy regimens specified in Arm A as clinically indicated. Patients then undergo a PET scan. Patients who achieve a CR or PR proceed to HDT-ASCT. Patients who achieve SD or PD come off study treatment. HDT-ASCT: Patients undergo ASCT. Patients may also receive a standard preparative chemotherapy regimen as clinically indicated. Patients who achieve PR prior to ASCT may also undergo RT as clinically indicated. Patients who went into ASCT with PR also undergo a PET/CT scan 30 days post-transplant. MAINTENANCE THERAPY: Patients may receive brentuximab vedotin IV as clinically indicated. All patients undergo CT scans during follow-up.
Study Type : | Interventional |
Estimated Enrollment : | 0 participants |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Randomized Phase III Trial of Chemotherapy vs. Pembrolizumab Plus Chemotherapy for Relapsed/Refractory Classical Hodgkin Lymphoma |
Actual Study Start Date : | August 10, 2023 |
Estimated Primary Completion Date : | June 30, 2028 |
Estimated Study Completion Date : | June 30, 2028 |
Arm | Intervention/treatment |
---|---|
Active Comparator: Arm A (chemotherapy regimen, HDT-ASCT) SALVAGE THERAPY: Patients receive 1 of 3 chemotherapy regimens as clinically indicated: 1) ifosfamide IV, carboplatin IV, and etoposide IV; 2) gemcitabine IV, vinorelbine IV, and pegylated liposomal doxorubicin IV; or 3) brentuximab vedotin IV and bendamustine IV. Patients then undergo a PET/CT scan. Patients who achieve a CR or PR proceed to HDT-ASCT. Patients who achieve SD or PD come off study treatment. HDT-ASCT: Patients undergo ASCT. Patients may also receive a standard preparative chemotherapy regimen as clinically indicated. Patients who achieve PR prior to ASCT may also undergo RT as clinically indicated. Patients who went into ASCT with PR also undergo a PET/CT scan 30 days post-transplant. MAINTENANCE THERAPY: Patients may receive brentuximab vedotin IV as clinically indicated. |
Procedure: Autologous Hematopoietic Stem Cell Transplantation Drug: Bendamustine Drug: Brentuximab Vedotin Drug: Carboplatin Procedure: Computed Tomography Drug: Etoposide Drug: Gemcitabine Drug: Ifosfamide Drug: Pegylated Liposomal Doxorubicin Hydrochloride Procedure: Positron Emission Tomography Radiation: Radiation Therapy Other: Transplant Conditioning Drug: Vinorelbine |
Experimental: Arm B (chemotherapy regimens+pembrolizumab, HD-ASCT) SALVAGE THERAPY: Patients receive pembrolizumab IV plus 1 of 3 chemotherapy regimens specified in Arm A as clinically indicated. Patients then undergo a PET scan. Patients who achieve a CR or PR proceed to HDT-ASCT. Patients who achieve SD or PD come off study treatment. HDT-ASCT: Patients undergo ASCT. Patients may also receive a standard preparative chemotherapy regimen as clinically indicated. Patients who achieve PR prior to ASCT may also undergo RT as clinically indicated. Patients who went into ASCT with PR also undergo a PET/CT scan 30 days post-transplant. MAINTENANCE THERAPY: Patients may receive brentuximab vedotin IV as clinically indicated. |
Procedure: Autologous Hematopoietic Stem Cell Transplantation Drug: Bendamustine Drug: Brentuximab Vedotin Drug: Carboplatin Procedure: Computed Tomography Drug: Etoposide Drug: Gemcitabine Drug: Ifosfamide Drug: Pegylated Liposomal Doxorubicin Hydrochloride Biological: Pembrolizumab Procedure: Positron Emission Tomography Radiation: Radiation Therapy Other: Transplant Conditioning |
Ages Eligible for Study: | 5 Years to 75 Years |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.