Obinutuzumab and ICE Chemotherapy in Refractory/Recurrent CD20+ Mature NHL

NCT ID: NCT02393157

Last Updated: 2025-08-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-21
• Study Completion Date: 2027-12-31

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).

Conditions

Non-Hodgkin Lymphoma; Burkitt Lymphoma; Diffuse Large B-Cell Lymphoma; Primary Mediastinal B-cell Lymphoma; CD20+ Lymphoblastic Lymphoma; Follicular Lymphoma, Grade III

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Obinutuzumab

Intervention Type: DRUG

Drug will be given alone in a pre-phase and in combination with ICE chemotherapy.

Liposomal ARA-C

Intervention Type: DRUG

Will be given intrathecally for both prophylaxis and treatment of CNS disease.

Ifosfamide

Intervention Type: DRUG

Ifosfamide 3000 mg/m2/day as a 2 hour IV infusion daily x 3 days (Days 0,1,2) of Cycle 1 and 2.

Carboplatin

Intervention Type: DRUG

Carboplatin: 635 mg/m2 as 1 hour IV infusion on Day 0 only of Cycle 1 and 2.

Etoposide

Intervention Type: DRUG

Etoposide: 100 mg/m2/day as 1 hour IV infusion daily x 3 days (Days 0,1,2).

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.

Group Type: EXPERIMENTAL

Obinutuzumab

Intervention Type: DRUG

Drug will be given alone in a pre-phase and in combination with ICE chemotherapy.

Liposomal ARA-C

Intervention Type: DRUG

Will be given intrathecally for both prophylaxis and treatment of CNS disease.

Ifosfamide

Intervention Type: DRUG

Ifosfamide 3000 mg/m2/day as a 2 hour IV infusion daily x 3 days (Days 0,1,2) of Cycle 1 and 2.

Carboplatin

Intervention Type: DRUG

Carboplatin: 635 mg/m2 as 1 hour IV infusion on Day 0 only of Cycle 1 and 2.

Etoposide

Intervention Type: DRUG

Etoposide: 100 mg/m2/day as 1 hour IV infusion daily x 3 days (Days 0,1,2).

Interventions

Obinutuzumab

Drug will be given alone in a pre-phase and in combination with ICE chemotherapy.

Intervention Type: DRUG

Liposomal ARA-C

Will be given intrathecally for both prophylaxis and treatment of CNS disease.

Intervention Type: 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.

Intervention Type: DRUG

Carboplatin

Carboplatin: 635 mg/m2 as 1 hour IV infusion on Day 0 only of Cycle 1 and 2.

Intervention Type: DRUG

Etoposide

Etoposide: 100 mg/m2/day as 1 hour IV infusion daily x 3 days (Days 0,1,2).

Intervention Type: DRUG

Other Intervention Names

Gazyva; Depocyte; Ifex; Paraplatin; VP-16

Eligibility 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

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 31 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Roswell Park Cancer Institute

OTHER

Sponsor Role: collaborator

New York Medical College

OTHER

Sponsor Role: lead

Responsible Party

Mitchell Cairo

Vice Chair

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mitchell Cairo, MD

Role: STUDY_CHAIR

New York Medical College

Locations

New York Medical College

Valhalla, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Mitchell Cairo, MD

Role: CONTACT

Mitchell_Cairo@nymc.edu

914-594-2150

Jessica Hochberg, MD

Role: CONTACT

jessica_hochberg@nymc.edu

914-594-2150

Facility Contacts

Jessica Hochberg, MD

Role: primary

jessica_hochberg@nymc.edu

914-594-2150

Mitchell Cairo, MD

Role: backup

mitchell_cairo@nymc.edu

914-594-2150

Other Identifiers

L-11,392

Identifier Type: -

Identifier Source: org_study_id