Obinutuzumab + ICE for Non-Hodgkin's Lymphoma

(O-ICE Trial)

Overseen By Jessica C. Hochberg

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: New York Medical College

Disqualifiers: Immune deficiency, Organ transplant, GVHD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks per cycle

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for children, adolescents, and young adults with relapsed CD20 positive B-cell Non-Hodgkin's Lymphoma (B-NHL), a type of blood cancer. Researchers are testing the safety and effectiveness of a drug called obinutuzumab (Gazyva), both alone and combined with a chemotherapy regimen known as ICE. Treatment approaches vary depending on whether the cancer has spread to the central nervous system. This trial suits those who have experienced relapse or treatment failure with specific types of B-cell lymphomas and have not previously received obinutuzumab. Participants should also have adequate organ function and no recent intense chemotherapy or radiation. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer treatment.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, you must not have received myelosuppressive chemotherapy within 2 weeks before joining the study, and there are specific timing requirements for prior radiation therapy and steroid treatments.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining obinutuzumab with ICE chemotherapy has been studied for safety in treating relapsed B-cell Non-Hodgkin Lymphoma (B-NHL). Patients in past studies generally tolerated this treatment well, though, like many cancer treatments, it can have side effects.

Obinutuzumab is a therapy that aids the immune system in identifying and attacking cancer cells. Its use in other blood cancers suggests it is relatively safe. Common side effects may include low blood cell counts, fever, and tiredness, typical for many cancer treatments.

ICE consists of ifosfamide, carboplatin, and etoposide, chemotherapy drugs long used in cancer treatment. They can cause side effects such as nausea, hair loss, and changes in blood counts, which are expected and usually manageable.

Overall, evidence from past studies indicates that while side effects exist, the treatment is generally considered safe enough for further research. Prospective participants should discuss expectations with their doctor before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination treatment of Obinutuzumab with ICE (Ifosfamide, Carboplatin, Etoposide) for Non-Hodgkin's Lymphoma because it adds a novel twist to existing therapies. Unlike standard treatments, which often don't integrate targeted antibodies, Obinutuzumab is a monoclonal antibody that specifically targets CD20 on B-cells, potentially enhancing the body's immune response against the cancer. Additionally, the use of Liposomal cytarabine for central nervous system (CNS) involvement or prophylaxis is unique, offering targeted delivery to the CNS which is not typically addressed in standard regimens. This approach not only aims to improve efficacy but also seeks to reduce the risk of CNS relapse, a common challenge in treating this type of lymphoma.

What evidence suggests that this trial's treatments could be effective for Non-Hodgkin's Lymphoma?

Research has shown that the ICE chemotherapy treatment, which includes ifosfamide, carboplatin, and etoposide, has reduced cancer in 72% of patients with non-Hodgkin's lymphoma. Many patients experienced tumor shrinkage after treatment. In this trial, researchers are testing Obinutuzumab, a drug that acts like an antibody, in combination with ICE to determine if it enhances the treatment's effectiveness. This new combination aims to assist children and young adults with relapsed B-cell non-Hodgkin's lymphoma, a cancer affecting the immune system. Early results suggest that adding Obinutuzumab might improve the treatment, but further research is necessary to confirm this. Participants in this trial will be divided into two groups based on CNS involvement to receive the combination therapy. ^{1 5 6 7 8}

Who Is on the Research Team?

Mitchell Cairo, MD

Principal Investigator

New York Medical College

Are You a Good Fit for This Trial?

This trial is for children, adolescents, and young adults with certain types of B-cell Non-Hodgkin Lymphoma that have relapsed or didn't respond to initial treatment. Participants need good organ function and a performance status score (Karnofsky/Lansky) above 60%. They shouldn't have had recent chemotherapy, radiation therapy in specific time frames, prior obinutuzumab treatment, or uncontrolled hepatitis.

Inclusion Criteria

I haven't had chemotherapy that lowers my blood cell counts in the last 2 weeks.

I have never been treated with obinutuzumab.

My cancer is a type of B-cell leukemia/lymphoma and is in its first relapse or did not respond to initial treatment.

Exclusion Criteria

I have been newly diagnosed with B-cell Non-Hodgkin's Lymphoma and have not received any treatment.

Known congenital or acquired immune deficiency

History of grade 4 anaphylactic reactions to humanized or murine monoclonal antibodies

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Prephase

Participants receive obinutuzumab and Liposomal cytarabine (for CNS positive) or prophylactic Liposomal cytarabine (for CNS negative) with dexamethasone

2 weeks

Multiple visits for drug administration

Treatment

Participants receive O-ICE chemotherapy in 21-day cycles, including obinutuzumab and ICE chemotherapy

3 weeks per cycle

Weekly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Etoposide
• Ifosfamide
• Obinutuzumab

Trial Overview The study tests the safety and response rate of obinutuzumab alone and combined with ICE chemotherapy (ifosfamide, carboplatin, etoposide) in treating relapsed CD20 positive B-cell Non-Hodgkin Lymphoma. It aims to find out how well this combination works for these patients.

How Is the Trial Designed?

Group I: Central Nervous System (CNS) Negative Experimental Treatment 5 Interventions

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 II: CNS Positive Experimental Treatment 5 Interventions

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.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

New York Medical College

Lead Sponsor

Trials

73

Recruited

8,700+

Roswell Park Cancer Institute

Collaborator

Trials

427

Recruited

40,500+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02393157

NCT02393157 | Obinutuzumab and ICE Chemotherapy in ... The purpose of this study is to determine the safety of administering obinutuzumab as a single agent alone and in combination with ifosfamide, carboplatin, ...

2. trial.medpath.com trial.medpath.com/clinical-trial/890546041dbe1eee/nct02393157-chemoimmunotherapy-obinutuzumab-ifosfamide-carboplatin-etoposide-children-adolescents-young-adults-recurrent

Obinutuzumab and ICE Chemotherapy in Refractory ... The purpose of this study is to determine the safety of administering obinutuzumab as a single agent alone and in combination with ifosfamide, carboplatin, ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)47368-7/fulltext

Ifosfamide, carboplatin, etoposide (ICE)-based second-line ... In a series of prospective clinical trials, 222 patients were treated with the ICE regimen, with an overall response rate of 72%.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10949171/

Refractory Burkitt Lymphoma: Diagnosis and Interventional ... Refractory Burkitt lymphoma still remains a therapeutic challenge, with dismal outcome. The prognosis is very poor, ranging from less than 10% to 30–40%.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0923753419473699

Outpatient-based ifosfamide, carboplatin and etoposide ... We have treated 38 transplant-eligible patients with relapsed/refractory non-Hodgkin's lymphoma and Hodgkin's disease using an outpatient-based regimen of ...

6. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT02393157/

Clinical Trial: NCT02393157 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 ...

7. touroscholar.touro.edu touroscholar.touro.edu/nymc_fac_abstracts/708/

"Phase II Trial of Obinutuzumab and Ice Chemotherapy in ... Objectives: To investigate the safety and activity of obinutuzumab (O) in combination with ifosfamide, carboplatin, and etoposide (ICE) in children, adolescents ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27054024/

Obinutuzumab for relapsed or refractory indolent non- ... In rituximab-refractory indolent NHL, the recent randomized phase III GADOLIN study demonstrated an improved median progression-free survival for patients ...