KITE-197 for Large B-cell Lymphoma

Recruiting at11 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Kite, A Gilead Company

Must not be taking: CD19 antibodies, Bendamustine, CAR therapy

Disqualifiers: Other malignancy, Richter's transformation, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new drug called KITE-197 for patients whose large B-cell lymphoma has returned or didn't respond to previous treatments. The study will first check if the drug is safe and find the best dose. Then, it will see if this dose can help eliminate the cancer completely. Another treatment for this type of lymphoma is available for those who have not responded to multiple previous treatments.

Do I need to stop my current medications for the KITE-197 trial?

The trial information does not specify whether you need to stop taking your current medications. However, certain prior treatments and conditions are listed as exclusion criteria, so it's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug KITE-197 for treating large B-cell lymphoma?

The research suggests that while current treatments for aggressive lymphomas like large B-cell lymphoma have limited long-term success, new approaches such as CAR T-cells, which are similar to KITE-197, show promise in treating relapsed cases due to their unique way of targeting cancer cells. ^{1 2 3 4 5}

Research Team

Kite Study Director

Principal Investigator

Kite, A Gilead Company

Eligibility Criteria

This trial is for individuals with relapsed or refractory Large B-cell Lymphoma who have at least one measurable lesion and proper organ and bone marrow function. It's not suitable for those who don't meet these health requirements.

Inclusion Criteria

My large B-cell lymphoma has returned or is not responding to treatment.

It looks like there might be a mistake or missing information in your request. Could you please provide more details or clarify the criterion you'd like to have rewritten in simpler language?

You have at least one lesion that can be measured.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1a (Dose Escalation)

Participants receive lymphodepleting chemotherapy followed by a single target starting dose of KITE-197. Additional participants are enrolled based on dose limiting toxicities observed.

Duration not specified

Phase 1b (Dose Expansion)

Participants receive lymphodepleting chemotherapy followed by a single dose of KITE-197 at a tolerable dose level.

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Long-term follow-up

Participants transition to a separate Kite long-term follow-up study for the remainder of the 15-year follow-up period.

Treatment Details

Interventions

• Cyclophosphamide (Alkylating agents)
• Fludarabine (Anti-metabolites)
• KITE-197 (CAR T-cell Therapy)

Trial Overview The study tests KITE-197, alongside Cyclophosphamide and Fludarabine, in two phases: Phase 1a focuses on safety, tolerability, and dosing; Phase 1b assesses the effectiveness of KITE-197 at the recommended dose by looking at remission rates.

Participant Groups

Group I: KITE-197 Experimental Treatment 3 Interventions

Phase 1a (Dose Escalation): Participants with r/r large B-cell lymphoma will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single target starting dose of KITE-197 chimeric antigen receptor (CAR) transduced autologous T cells. Based on dose limiting toxicities (DLTs) observed in the first cohort, additional participants will be enrolled and administered escalating dose of KITE-197. Phase 1b (Dose Expansion): After completion of dose escalation, additional participants with r/r B-cell lymphoma across different disease indications will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single dose of KITE-197 CAR-transduced autologous T cells at 1 or more dose-level deemed to be tolerable.

Who Is Running the Clinical Trial?

Kite, A Gilead Company

Lead Sponsor

Trials

45

Recruited

4,300+

Findings from Research

Recent advancements in treating diffuse large B cell lymphoma have led to improved patient outcomes, particularly through dose-dense chemotherapy regimens and the combination of rituximab with chemotherapy, resulting in higher response rates and longer survival.

While low-risk patients have seen significant improvements, high-risk patients still require more effective strategies, potentially through better understanding of genetic factors that contribute to treatment resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current strategies for the treatment of diffuse large B cell lymphoma. Coiffier, B.[2019]

Only 40% of patients with aggressive non-Hodgkin's lymphoma achieve long-term remission with standard CHOP chemotherapy, highlighting the need for improved treatment strategies.

Current research is focusing on personalized treatment approaches, including the use of prognostic factors to identify patients who may benefit from aggressive therapy, as well as integrating novel therapies like immunotherapy and radioimmunotherapy to enhance outcomes, especially for elderly patients who are more vulnerable to intensive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current treatment options in aggressive lymphoma. Marcus, R.[2019]

A Paediatric Strategy Forum highlighted the need for focused drug development for children with B-cell malignancies, particularly emphasizing the importance of creating effective treatments for relapsed and refractory cases, as current frontline therapies are successful but come with significant toxicity.

Clinicians agreed that therapies like CAR T-cells, T-cell engagers, and antibody drug conjugates show the most promise for treating relapsed B-cell malignancies, although the lengthy production time for CAR T-cells limits their immediate use in acute situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ACCELERATE and European Medicine Agency Paediatric Strategy Forum for medicinal product development for mature B-cell malignancies in children. Pearson, ADJ., Scobie, N., Norga, K., et al.[2020]

In a phase II trial involving 25 adults with newly diagnosed Burkitt's lymphoma, the combination of liposomal doxorubicin and rituximab achieved a remarkable overall response rate of 100%, with 92% of patients reaching complete remission.

At a median follow-up of 34 months, the 2-year progression-free survival rate was 80% and overall survival rate was 84%, particularly notable for high-risk, HIV-negative patients who had even better outcomes with 84% PFS and 89% OS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter phase II study incorporating high-dose rituximab and liposomal doxorubicin into the CODOX-M/IVAC regimen for untreated Burkitt's lymphoma. Evens, AM., Carson, KR., Kolesar, J., et al.[2022]

The BLK88 treatment protocol, which includes high doses of chemotherapy and CNS prophylaxis, showed promising results in treating pediatric B cell non-Hodgkin's lymphoma and acute lymphoblastic leukemia, with 4 out of 6 patients in advanced stages remaining in complete remission after treatment.

Despite some side effects like neutropenia and liver dysfunction, which were manageable, the BLK88 protocol proved to be more effective than historical controls, where all patients in advanced stages relapsed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemotherapy for B lymphoid malignancy in childhood--results in BLK88 protocol]. Hibi, S., Fujiwara, F., Hashida, T., et al.[2015]

References

1. United States pubmed.ncbi.nlm.nih.gov

Current strategies for the treatment of diffuse large B cell lymphoma. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Current treatment options in aggressive lymphoma. [2019]

3. England pubmed.ncbi.nlm.nih.gov

ACCELERATE and European Medicine Agency Paediatric Strategy Forum for medicinal product development for mature B-cell malignancies in children. [2020]

4. England pubmed.ncbi.nlm.nih.gov

A multicenter phase II study incorporating high-dose rituximab and liposomal doxorubicin into the CODOX-M/IVAC regimen for untreated Burkitt's lymphoma. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

[Chemotherapy for B lymphoid malignancy in childhood--results in BLK88 protocol]. [2015]