CLN-978 for B-Cell Lymphoma

Recruiting at 5 trial locations

Overseen By Maria Akhondzadeh

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Cullinan Oncology, LLC

Must not be taking: CD19 antibodies, CAR-T

Disqualifiers: CNS lymphoma, Cardiac disease, Autoimmune, Infections, others

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

Compensation: Varies

Number of Visits: Unknown

90 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, certain treatments like recent chemotherapy, monoclonal antibodies, or radiation therapy may need to be paused before starting the trial.

What safety data exists for CLN-978 or similar treatments for B-Cell Lymphoma?

The safety of treatments similar to CLN-978, such as Bruton tyrosine kinase inhibitors used in B-Cell Lymphoma, has been studied, showing common side effects like high blood pressure and low blood cell counts. These treatments are generally well-tolerated, but they can have serious side effects, so careful monitoring is important. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial is testing a new experimental drug called CLN-978 in patients with a type of cancer that has come back or not responded to other treatments. The drug aims to either attack the cancer cells directly or help the immune system fight the cancer.

Eligibility Criteria

This trial is for adults with B-cell Non-Hodgkin Lymphoma that has come back or didn't respond to treatment. They must have tried at least two prior therapies and be in fairly good physical shape (ECOG PS ≤ 2). People can't join if they've had certain recent treatments, like CAR-T therapy, organ transplants, or are pregnant. Also excluded are those with autoimmune diseases needing immune suppression, active infections including COVID-19, or significant heart disease.

Inclusion Criteria

Measurable disease defined as specific criteria on imaging

Laboratory parameters meeting specified ranges

I can take care of myself and perform daily activities.

Exclusion Criteria

I have a serious brain or spinal cord condition.

I have or had cancer types other than the one I'm seeking treatment for.

My lymphoma affects my brain or central nervous system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Patients with R/R B-NHL treated with CLN-978 in dose escalation cohorts

24 months

Dose Expansion

Patients with R/R DLBCL, R/R FL and other R/R B-NHL treated with CLN-978 at a dose selected from the Part A Dose Escalation arm

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• CLN-978

Trial Overview The study tests CLN-978 in patients whose B-NHL has relapsed or hasn't responded to other treatments. It's an early-phase trial where researchers first find the best dose of CLN-978 and then see how well it works on different types of this lymphoma.

Participant Groups

Group I: Part B Dose Expansion Experimental Treatment 1 Intervention

Patients with R/R DLBCL, R/R FL and other R/R B-NHL treated with CLN-978 at a dose selected from the Part A Dose Escalation arm.

Group II: Part A Dose Escalation Experimental Treatment 1 Intervention

Patients with R/R B-NHL treated with CLN-978 in dose escalation cohorts

Who Is Running the Clinical Trial?

Cullinan Oncology, LLC

Lead Sponsor

Trials

7

Recruited

990+

Cullinan Therapeutics Inc.

Lead Sponsor

Trials

9

Recruited

1,000+

Cullinan Oncology Inc.

Lead Sponsor

Trials

6

Recruited

710+

Findings from Research

New-generation Bruton tyrosine kinase inhibitors (BTKi) show a high overall response rate of 92% in treating chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), particularly benefiting younger patients and those receiving combination therapy.

While BTKi-based therapies are generally well-tolerated, they can lead to significant adverse events like cytopenia and hypertension, and zanubrutinib may offer better efficacy than acalabrutinib as a monotherapy for CLL/SLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of new-generation Bruton tyrosine kinase inhibitors in chronic lymphocytic leukemia/small lymphocytic lymphoma: a systematic review and meta-analysis. Yin, S., Zheng, X., Zhang, W., et al.[2023]

Acalabrutinib, a Bruton's tyrosine kinase inhibitor, has been shown to be effective and safe for treating chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), with significant improvements in efficacy observed in both monotherapy and combination treatments.

In clinical studies, acalabrutinib demonstrated a high rate of molecular remission when combined with venetoclax, while maintaining an acceptable safety profile, although some adverse events occurred in over 20% of patients, including myelosuppression and gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib and its use in the treatment of chronic lymphocytic leukemia. Egyed, M., Lueff, S., Borbely, J., et al.[2022]

The combination therapy of obinutuzumab and ibrutinib, following a debulking phase with bendamustine, resulted in a 100% overall response rate in 61 patients with chronic lymphocytic leukemia (CLL), demonstrating its high efficacy.

The treatment was generally safe, with the most common severe side effects being neutropenia (14.8%) and thrombocytopenia (13.1%), and only one reported fatality, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CLL2-BIG: sequential treatment with bendamustine, ibrutinib and obinutuzumab (GA101) in chronic lymphocytic leukemia. von Tresckow, J., Cramer, P., Bahlo, J., et al.[2022]

Recent advancements in chronic lymphocytic leukemia (CLL) treatment, particularly with small molecule inhibitors, have shown significant clinical efficacy in both untreated and relapsed patients, but they also come with increased risks of specific adverse events.

An individualized treatment approach is now possible with targeted therapies like B-cell receptor inhibitors and venetoclax, emphasizing the need for a thorough understanding of their mechanisms, efficacy, and side effects to optimize patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimizing and managing treatment-associated complications in patients with chronic lymphocytic leukemia. Iskierka-Jażdżewska, E., Robak, T.[2021]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of new-generation Bruton tyrosine kinase inhibitors in chronic lymphocytic leukemia/small lymphocytic lymphoma: a systematic review and meta-analysis. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Acalabrutinib and its use in the treatment of chronic lymphocytic leukemia. [2022]

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

CLL2-BIG: sequential treatment with bendamustine, ibrutinib and obinutuzumab (GA101) in chronic lymphocytic leukemia. [2022]

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

Minimizing and managing treatment-associated complications in patients with chronic lymphocytic leukemia. [2021]

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

Clinical roundtable monograph. New alternatives in CLL therapy: managing adverse events. [2011]