What side effects are associated with this type of intervention?

Common treatments for Richter Syndrome, including autologous cellular immunotherapy like Lisocabtagene Maraleucel, can have several side effects. These include severe infusion-related reactions, such as fever, chills, and respiratory issues, as well as cytokine release syndrome, which can cause high fever and low blood pressure. Other treatments, such as chemotherapy and monoclonal antibodies (e.g., rituximab), may lead to side effects like nausea, fatigue, leukopenia, and increased susceptibility to infections. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

Richter Syndrome, a transformation of chronic lymphocytic leukemia (CLL) into a more aggressive form of lymphoma, has limited FDA-approved treatments specifically targeting it. However, treatments similar to Lisocabtagene Maraleucel, such as CAR-T cell therapies, have been approved for other types of lymphomas. For instance, Yescarta (axicabtagene ciloleucel) and Kymriah (tisagenlecleucel) are FDA-approved CAR-T cell therapies for certain types of large B-cell lymphomas, which share some treatment principles with Richter Syndrome. These therapies involve modifying a patient's own T-cells to target and kill cancer cells, similar to the approach being studied with Lisocabtagene Maraleucel.

What other types of research exist?

Promising novel alternatives to Lisocabtagene Maraleucel for Richter Syndrome patients include: 1) Axicabtagene Ciloleucel (Yescarta), an FDA-approved CAR T-cell therapy for relapsed/refractory large B-cell lymphoma, which has shown favorable efficacy and safety profiles. 2) Venetoclax plus Obinutuzumab, which has demonstrated improved progression-free survival and acceptable tolerability in chronic lymphocytic leukemia, a related condition. These alternatives should be discussed with a healthcare provider to determine the best treatment plan.

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Kinase Inhibitor

Liso-cel + Nivolumab + Ibrutinib for Richter Syndrome

Phase 2

Recruiting

Led By Tanya Siddiqi

Research Sponsored by City of Hope Medical Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of three treatments for patients with a type of cancer called Richter's transformation. The treatments include a personalized cell therapy, an immune-boosting drug, and a drug that stops cancer cells from growing. The goal is to see if this combination can better fight the cancer. Richter transformation is a condition where chronic lymphocytic leukemia (CLL) transforms into a more aggressive form of lymphoma.

Who is the study for?

Adults (18+) with Richter's Transformation who've had at least two prior systemic therapies or relapsed within a year of first-line chemoimmunotherapy. They must have adequate organ function, not require oxygen supplementation, and agree to use effective birth control. Excluded are those with HIV, active hepatitis B/C, recent heart issues, autoimmune diseases (except mild conditions like controlled asthma), recent stem cell transplants, or on certain medications.

What is being tested?

The trial is testing the combination of lisocabtagene maraleucel (liso-cel), nivolumab, and ibrutinib for treating Richter's transformation. Liso-cel uses the patient's own immune cells to fight cancer; nivolumab helps slow cancer growth by aiding the immune system; and ibrutinib blocks proteins that tell cancer cells to multiply.

What are the potential side effects?

Potential side effects include immune system reactions causing inflammation in various organs, infusion-related reactions from liso-cel or nivolumab administration, fatigue from all three drugs being tested as well as possible liver enzyme changes due to ibrutinib.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Complete Response (CR)

Unacceptable Toxicity (UT)

Secondary study objectives

Best Complete Response (CR)

Duration of Response (DOR)

Minimal Residual Disease (MRD)

+4 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (nivolumab, ibrutinib, chemotherapy, liso-cel)Experimental Treatment11 Interventions

Patients receive ibrutinib PO, nivolumab IV, fludarabine IV, cyclophosphamide IV, and liso-cel IV on study. Patients also undergo apheresis, PET/CT, biospecimen collection, and bone marrow biopsy on study. Patients may receive low-moderate intensity chemotherapy in combination with the study induction therapy per treating physician discretion with approval of study principal investigator.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biospecimen Collection

2004

Completed Phase 3

~2030

Nivolumab

2015

Completed Phase 3

~4010

Bone Marrow Biopsy

2021

Completed Phase 3

~230

Computed Tomography

2017

Completed Phase 2

~2790

Cyclophosphamide

2010

Completed Phase 4

~2310

Fludarabine

2012

Completed Phase 4

~1860

Ibrutinib

2014

Completed Phase 4

~2060

Biopsy

2014

Completed Phase 4

~1150

Pheresis

2017

Completed Phase 2

~10

Positron Emission Tomography

2011

Completed Phase 2

~2200

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Richter Syndrome, a transformation of chronic lymphocytic leukemia into a more aggressive form of lymphoma, is treated with various advanced therapies. Lisocabtagene Maraleucel (Liso-cel) is an autologous cellular immunotherapy that uses the patient's own modified T-cells to target and kill cancer cells, enhancing the body's immune response against the malignancy. Nivolumab, a monoclonal antibody, works by inhibiting the PD-1 pathway, thereby boosting the immune system's ability to attack cancer cells. Ibrutinib, a kinase inhibitor, blocks the activity of Bruton's tyrosine kinase (BTK), which is essential for the growth and survival of cancer cells. These treatments are crucial for Richter Syndrome patients as they offer targeted and effective options that can potentially lead to better outcomes by directly attacking the cancer cells and supporting the immune system's role in combating the disease.

Successful low-dose chemotherapy for refractory Epstein-Barr virus-related post-transplant lymphoproliferative disorder following hematopoietic stem cell transplantation in a child with Wiskott-Aldrich syndrome.Serendipity in splendid isolation: rapamycin.Rituximab for the treatment of post-bone marrow transplantation refractory hemolytic anemia in a child with Omenn's syndrome.