CD70.CAR NK Cells for Non-Hodgkin's and Hodgkin's Lymphoma

Overseen By Yago Nieto, MD,PHD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Active infection, HIV, CNS involvement, 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: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new therapy using CD70.CAR NK cells, a type of immunotherapy, can manage certain types of lymphoma, specifically Non-Hodgkin's and Hodgkin's, when standard treatments have failed or the disease has recurred quickly. Participants will receive a combination of chemotherapy and CD70.CAR NK cells to assess if this approach can better control the cancer. Suitable candidates have either type of lymphoma that hasn't responded well or has returned within a year of initial treatment, and have a tumor that tests positive for CD70. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on systemic steroid therapy or immunosuppressive therapy. It's best to discuss your specific medications with the trial team.

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

Studies have shown that CD70.CAR NK cells are generally safe for humans. Research indicates that these cells can target cancer cells more precisely, potentially reducing the risk of harming healthy cells. This precision could lead to fewer side effects compared to some traditional cancer treatments.

In previous studies, CD70-targeted CAR-NK cells attacked cancer cells in several ways, making them potentially more effective without increasing risks. Importantly, they function without needing MHC, a molecule that helps the immune system recognize cells, which might lower the risk of severe immune reactions.

Although specific data from this trial phase is not available, their testing in a Phase 2 trial indicates they have already passed initial safety tests in earlier trials, suggesting they are well-tolerated in humans so far. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for non-Hodgkin's and Hodgkin's lymphoma, which typically involve chemotherapy and immunotherapy, CD70.CAR NK cells are a cutting-edge approach that utilizes genetically modified natural killer (NK) cells to target and destroy cancer cells. Researchers are excited about these treatments because they harness the body's own immune system with a new mechanism that specifically targets CD70, a protein found on the surface of some cancer cells. This targeted approach not only promises to be more effective in attacking the cancer cells but also potentially reduces the side effects associated with traditional therapies. Additionally, the combination with Rimiducid offers a unique strategy to enhance the activation and persistence of the therapeutic NK cells, making it a promising option for patients who have not responded well to existing treatments.

What evidence suggests that CD70.CAR NK cell therapy might be an effective treatment for lymphoma?

Studies have shown that CD70.CAR NK cells effectively target certain cancer cells. These cells outperform some other treatments in destroying lymphoma cells lacking CD19 markers. One study showed that treatments targeting CD70 had an 89% success rate in controlling other advanced cancers. Research indicates that these cells possess strong cancer-fighting abilities both in lab tests and in living organisms. This trial will evaluate CD70.CAR NK cell therapy as a promising option for treating hard-to-treat lymphomas like DLBCL and cHL, with participants receiving either a first or second dose of the treatment. ^{1 2 3 4 5}

Who Is on the Research Team?

Yago Nieto, MD,PHD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with early relapsed or primary refractory Diffuse Large B-Cell Lymphoma (DLBCL) and Hodgkin Lymphoma (cHL), who haven't responded well to initial treatments. Participants must have a tumor positive for CD70, measurable disease on PET/CT scan, be relatively fit (ECOG PS ≤ 2), and have adequate organ function.

Inclusion Criteria

1. 18-75 years of age.

* Primary refractory, defined as not having achieved a CR with frontline therapy or having relapsed within 3 months.

* Early relapsed (≤ 12 months) after achieving a CR to frontline therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Patients receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide from days -5 to -3

1 week

Treatment

Infusion of CD70.CAR NK cells on day 0, with Rimiducid, on an outpatient or inpatient basis as clinically indicated

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• CD70.CAR NK Cells

Trial Overview The study tests if CD70.CAR NK cell therapy can control DLBCL and cHL that hasn't responded to first-line treatments. It includes pre-treatment with Fludarabine and Cyclophosphamide, followed by the experimental NK cell therapy, with Rimiducid used as needed.

How Is the Trial Designed?

Group I: 2nd Dose: Treatment with Rimiducid + CD70.CAR NK Cells for Patients with DLBCL and HL Experimental Treatment 4 Interventions

Patients will receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide from days -5 to -3, prior to infusion of CD70.CAR NK cells on day 0, on an outpatient or inpatient as clinically indicated.

Group II: 1st Dose: Treatment with Rimiducid + CD70.CAR NK Cells for Patients with DLBCL and HL Experimental Treatment 4 Interventions

Patients will receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide from days -5 to -3, prior to infusion of CD70.CAR NK cells on day 0, on an outpatient or inpatient as clinically indicated.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Bellicum Pharmaceuticals

Industry Sponsor

Trials

28

Recruited

1,400+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07164469

NCT07164469 | Phase 2 Trial of CD70.CAR NK Cells for ... This clinical research study is to learn if CD70.CAR NK cell therapy can help to control early relapsed or primary refractory DLBCL and cHL.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12522704/

CD70-targeted CAR-T/NK therapy - PubMed Central - NIH B cell lymphomas​​ Pre-clinical work demonstrates that CD70 CAR-T cells eliminate CD19⁺/CD70⁺ Raji cells more effectively than CD19 CAR-T cells at low effector- ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666379124006608

CD70-targeted iPSC-derived CAR-NK cells display potent ... ALLO-316 (CD70 CAR-T) shows an 89% disease control rate in treating advanced or metastatic RCCs. In addition, natural killer (NK) cells ...

4. ashpublications.org ashpublications.org/bloodadvances/article/8/11/2635/515576/CD70-specific-CAR-NK-cells-expressing-IL-15-for

CD70-specific CAR NK cells expressing IL-15 for the ... CD70-CAR NK cells displayed superior cytotoxic activity in vitro and in vivo against CD19-negative B-cell lymphoma when compared with nontransduced NK cells ...

5. withpower.com withpower.com/trial/phase-2-hodgkin-disease-1-2026-efeba

CD70.CAR NK Cells for Non-Hodgkin's and ... This clinical research study is to learn if CD70.CAR NK cell therapy can help to control early relapsed or primary refractory DLBCL and cHL. Show more ...