|
| Overall Recruitment Status: Active, currently enrolling |
| |
| Official Title |
| A Phase III, Randomized Study of Nivolumab (Opdivo) Plus AVD or Brentuximab Vedotin (Adcetris) Plus AVD in Patients (Age >/= 12 Years) With Newly Diagnosed Advanced Stage Classical Hodgkin Lymphoma |
| |
| Region |
Sponsors |
| Colorado |
|
| |
| Acronym |
KP IRB No. |
|
1765616 |
| |
| Study Type |
Phase |
| Clinical Trial |
Phase III |
| |
| Study Population Description |
| (Child, Adult, Older Adult) with Ann Arbor Stage III Hodgkin Lymphoma
Ann Arbor Stage III Lymphocyte-Depleted Classic Hodgkin Lymphoma
Ann Arbor Stage III Mixed Cellularity Classic Hodgkin Lymphoma
Ann Arbor Stage III Nodular Sclerosis Classic Hodgkin Lymphoma
Ann Arbor Stage IIIA Hodgkin Lymphoma
Ann Arbor Stage IIIB Hodgkin Lymphoma
Ann Arbor Stage IV Hodgkin Lymphoma
Ann Arbor Stage IV Lymphocyte-Depleted Classic Hodgkin Lymphoma
Ann Arbor Stage IV Mixed Cellularity Classic Hodgkin Lymphoma
Ann Arbor Stage IV Nodular Sclerosis Classic Hodgkin Lymphoma
Ann Arbor Stage IVA Hodgkin Lymphoma
Ann Arbor Stage IVB Hodgkin Lymphoma
Classic Hodgkin Lymphoma
Lymphocyte-Rich Classic Hodgkin Lymphoma |
| |
| Purpose |
| This phase III trial compares immunotherapy drugs (nivolumab or brentuximab vedotin) when given with combination chemotherapy in treating patients with newly diagnosed stage III or IV classic Hodgkin lymphoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to cancer cells in a targeted way and delivers vedotin to kill them. Chemotherapy drugs, such as doxorubicin, vinblastine, and dacarbazine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. The addition of nivolumab or brentuximab vedotin to combination chemotherapy may shrink the cancer or extend the time without disease symptoms coming back. |
| |
| Detailed Description |
| PRIMARY OBJECTIVE:
I. To compare the progression-free survival (PFS) in patients with newly diagnosed advanced stage classical Hodgkin lymphoma randomized to N-AVD (nivolumab, doxorubicin hydrochloride [doxorubicin], vinblastine sulfate [vinblastine], dacarbazine) versus that obtained with BV-AVD (brentuximab vedotin, doxorubicin, vinblastine, dacarbazine).
SECONDARY OBJECTIVES:
I. To compare overall survival (OS) in patients randomized to N-AVD versus BV-AVD.
II. To compare event-free survival (EFS) in patients randomized to N-AVD versus BV-AVD.
III. To compare the metabolic complete response (CR) rate at the end of treatment in patients randomized to N-AVD versus BV-AVD.
IV. To compare the physician-reported treatment-related adverse event rates between arms stratified by age groups.
V. To compare patient-reported symptoms using selected Patient Reported Outcome Common Toxicity Criteria for Adverse Events (PRO-CTCAE) items between arms stratified by age groups.
VI. To compare the safety and tolerability of N-AVD versus that of BV-AVD.
QUALITY OF LIFE OBJECTIVE:
I. To compare between arms patient-reported fatigue, neuropathy and health-related quality of life over time (baseline, beginning of cycle 3, 4-8 weeks after the last dose of protocol therapy [following last dose of study drug or radiation therapy, whichever is later], and 1 and 3 years after randomization) using the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue, the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), and the PROMIS Global, respectively.
BANKING OBJECTIVES:
I. To bank specimens for future correlative studies. II. To bank positron emission tomography (PET)-computed tomography (CT) images for future correlative studies.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive doxorubicin hydrochloride intravenously (IV), vinblastine sulfate IV, dacarbazine IV, and nivolumab IV over 30 minutes on days 1 and 15. Patients may receive pegfilgrastim subcutaneously (SC) on days 2 and 16, or filgrastim SC or IV on days 6-10 and 21-25. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of cycle 6, patients may receive radiation therapy 5 days per week for approximately 4 weeks at the discretion of the treating physician.
ARM II: Patients receive doxorubicin hydrochloride IV, vinblastine sulfate IV, dacarbazine IV, and brentuximab vedotin IV over 30 minutes on days 1 and 15. Patients may receive pegfilgrastim SC on days 2 and 16, or filgrastim SC or IV on days 6-10 and 21-25. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of cycle 6, patients may receive radiation therapy 5 days per week for approximately 4 weeks at the discretion of the treating physician.
After completion of study treatment and prior to disease progression, patients are followed up every 3 months for the first year, every 6 months for years 2 and 3, then annually until 10 years after registration. Patients are followed up at the time of progression and then annually until 10 years after registration. Patients who receive radiation therapy are followed up at 8-12 weeks after completion of radiation therapy. |
| |
| Gender |
Age Limit |
| Male & Female |
12 years & older |
| |
- All patients must have histologically confirmed newly diagnosed, previously untreated stage III or IV classical Hodgkin lymphoma (nodular sclerosing, mixed cellularity, lymphocyte-rich, or lymphocyte-depleted, or not otherwise specified [NOS]). Nodular lymphocyte predominant Hodgkin lymphoma is not eligible
|
-
Patients must have bidimensionally measurable disease (at least one lesion with longest diameter >= 1.5 cm) documented on the Lymphoma Baseline Tumor Assessment Form in Rave
|
-
Patients must have a whole body or limited whole body PET-CT scan performed within 42 days prior to registration. (A contrast-enhanced [diagnostic] CT, MRI or MR-PET is acceptable in event that PET-CT is contra-indicated, however if it is later possible to administer a PET-CT, then PET-CT is strongly preferred for the interim scan (after cycle 2) (if performed) and the EOT assessment. Otherwise, if PET-CT is not subsequently possible, then the same modality as baseline must be used throughout the trial.) NOTE: All images from PET-CT, CT, MRI or MR-PET scans performed as standard of care to assess disease (within 42 days prior to registration) must be submitted and associated radiology reports must be submitted
|
-
Patients must not have received any prior chemotherapy, radiation, or antibody-based treatment for classical Hodgkin lymphoma. Steroid pre-treatment is permitted
|
-
Patients must not have had prior solid organ transplant
|
-
Patients must not have had prior allogeneic stem cell transplantation
|
-
Please contact study team for additional inclusion criteria
|
- Please contact study team for exclusion criteria
|
|
| |
-
Antibiotics, Antineoplastic
|
|
|
|
|
|
|
|
|
|
|
-
Antineoplastic Agents, Immunological
|
-
Lymphoproliferative Disorders
|
|
|
|
|
|
-
Neoplasms by Histologic Type
|
|
|
|
|
|
|
|
|
|
|
|
-
Physiological Effects of Drugs
|
|
|
|
|
|
-
Topoisomerase II Inhibitors
|
|
|
|
|
|
|
-
Immunoproliferative Disorders
|
|
|
| |
|