O-ICE: Obinutuzumab and ICE Chemotherapy in Refractory/Recurrent CD20+ Mature NHL
Study Details
Study Description
Brief Summary
The purpose of this study is to determine the safety of administering obinutuzumab as a single agent alone and in combination with ifosfamide, carboplatin, and etoposide (ICE) chemotherapy and determine the response rate of this treatment for children, adolescents and young adults (CAYA) with relapsed CD20 positive B-cell Non-Hodgkin Lymphoma (B-NHL).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Central Nervous System (CNS) Negative All patients will receive 4 doses of obinutuzumab on days -14, -10, -6 and -2. Patients without CNS involvement will receive one dose of Liposomal cytarabine for CNS prophylaxis on day -13. Dexamethasone will be given for 5 days with each Liposomal cytarabine dose starting one day prior to the Liposomal cytarabine. Dexamethasone 0.15 mg/kg/dose (max 4mg) IV BID will be given days -14 to -10. Following completion of the Prephase (or at the first sign of progressive disease), all patients will proceed to cycle 1 of O-ICE. O-ICE chemotherapy is given in 21-day (3-week) cycles. Three weekly doses of obinutuzumab will be given days -2 (during the prephase), +6 and +13. Patients will receive ICE chemotherapy (ifosfamide-carboplatin-etoposide) administered on Days 0-2 of Cycle 1. |
Drug: Obinutuzumab
Drug will be given alone in a pre-phase and in combination with ICE chemotherapy.
Other Names:
Drug: Liposomal ARA-C
Will be given intrathecally for both prophylaxis and treatment of CNS disease.
Other Names:
Drug: Ifosfamide
Ifosfamide 3000 mg/m2/day as a 2 hour IV infusion daily x 3 days (Days 0,1,2) of Cycle 1 and 2.
Other Names:
Drug: Carboplatin
Carboplatin: 635 mg/m2 as 1 hour IV infusion on Day 0 only of Cycle 1 and 2.
Other Names:
Drug: Etoposide
Etoposide: 100 mg/m2/day as 1 hour IV infusion daily x 3 days (Days 0,1,2).
Other Names:
|
| Experimental: CNS Positive All patients will receive 4 doses of obinutuzumab on days -14, -10, -6 and -2. Patients with positive CSF prior to enrollment will receive treatment with two doses of Liposomal cytarabine during the prephase portion of therapy. Liposomal cytarabine will be given intrathecally on days -13 and -5. Dexamethasone will be given for 5 days with each Liposomal cytarabine dose starting the day prior to the Liposomal cytarabine. Dexamethasone will be given days -14 to -10 and days -6 through -2. Following completion of the Prephase (or at the first sign of progressive disease), all patients will proceed to cycle 1 of O-ICE. O-ICE chemotherapy is given in 21-day (3-week) cycles. Three weekly doses of obinutuzumab will be given days -2 (during the prephase), +6 and +13. Patients will receive ICE chemotherapy (ifosfamide-carboplatin-etoposide) administered on Days 0-2 of Cycle 1. |
Drug: Obinutuzumab
Drug will be given alone in a pre-phase and in combination with ICE chemotherapy.
Other Names:
Drug: Liposomal ARA-C
Will be given intrathecally for both prophylaxis and treatment of CNS disease.
Other Names:
Drug: Ifosfamide
Ifosfamide 3000 mg/m2/day as a 2 hour IV infusion daily x 3 days (Days 0,1,2) of Cycle 1 and 2.
Other Names:
Drug: Carboplatin
Carboplatin: 635 mg/m2 as 1 hour IV infusion on Day 0 only of Cycle 1 and 2.
Other Names:
Drug: Etoposide
Etoposide: 100 mg/m2/day as 1 hour IV infusion daily x 3 days (Days 0,1,2).
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Safety as assessed by adverse reactions and events [1 month]
Patients will be monitored for adverse reactions and events of drug when given alone and in combination with ICE chemotherapy.
- Response rate assessed following each treatment cycle for regression of tumor [3 months]
Patients will be assessed following each treatment cycle for regression of tumor.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients in first relapse or primary induction failure CD20 positive B-cell leukemia/lymphoma including:
-
Diffuse Large B-Cell Lymphoma
-
Burkitt Lymphoma
-
High Grade B-cell Lymphoma: Not Otherwise Specified (NOS)
-
Primary mediastinal B-cell lymphoma (PMBL)
-
CD20+ B-lymphoblastic lymphoma
-
Follicular lymphoma, Grade III
-
Karnofsky ≥ 60% for patients > 16 years of age and
-
Lansky ≥ 60 for patients ≤ 16 years of age.
-
Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry onto this study.
-
Patients may not have received prior therapy with obinutuzumab (GA101)
-
Radiation Therapy (XRT): Date of receiving prior XRT must be > 2 weeks for local palliative XRT (small port); > 6 months must have elapsed if prior craniospinal XRT or if > 50% radiation of pelvis; > 6 weeks must have elapsed if other substantial bone marrow radiation.
-
Steroids: Patients may have received prior steroid treatment, but not started greater than 7 days prior to initiation of protocol therapy.
-
Adequate organ function.
Exclusion Criteria:
-
Patients with newly diagnosed, previously untreated B-NHL.
-
Known congenital or acquired immune deficiency.
-
Prior solid organ transplantation.
-
Prior allogeneic stem cell transplant within 60 days or active acute Graft-vs-Host-Disease (GVHD) grade 3 or higher.
-
History of grade 4 anaphylactic reactions to humanized or murine monoclonal antibodies
-
Uncontrolled hepatitis B and/or C infection
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | New York Medical College | Valhalla | New York | United States | 10595 |
Sponsors and Collaborators
- New York Medical College
- Roswell Park Cancer Institute
Investigators
- Study Chair: Mitchell Cairo, MD, New York Medical College
- Principal Investigator: Matthew Barth, MD, Roswell Park Cancer Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- L-11,392