IL-21 Expanded Natural Killer Cells for Leukemia

Not currently recruiting at 1 trial location

Overseen By Nicole Szuminski

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sumithira Vasu

Must not be taking: Chemotherapy, Targeted therapy

Disqualifiers: Uncontrolled infection, Cardiac disease, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new immunotherapy using special immune cells called natural killer (NK) cells to treat acute myeloid leukemia (AML) that has returned or not responded to other treatments. The goal is to determine if these modified NK cells can stop the cancer from growing and spreading. Participants will receive a conditioning regimen followed by doses of membrane-bound Interleukin-21-expanded haploidentical NK cells. Suitable candidates for this trial are those with AML that has relapsed or not responded to previous treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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, you cannot be on any concurrent therapy like chemotherapy, targeted therapy, radiation therapy, or immunotherapy for your leukemia while participating in this trial.

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

Research has shown that using natural killer (NK) cells, a type of immune cell, is generally safe for treating certain leukemias, such as acute myeloid leukemia (AML). Studies have found that these NK cells, especially when enhanced with interleukin-21 (IL-21), are well-tolerated by patients with AML who have a poor prognosis, meaning most do not experience severe side effects.

Previous patients who received similar NK cell treatments did not encounter significant negative effects, suggesting these treatments can be safe. However, since this is an early study, the main goal is to identify any side effects to ensure the treatment's safety for humans.

While early results are promising, the trial is still in its initial stages to fully understand safety. For those considering participation, it is reassuring that the treatment has shown potential without major safety concerns in early experiences. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for leukemia, which often involve chemotherapy or stem cell transplants, membrane-bound Interleukin-21-expanded natural killer (NK) cells offer a novel approach by leveraging the body's own immune system. These NK cells are enhanced with Interleukin-21, a protein that boosts their cancer-fighting abilities, potentially improving their effectiveness against leukemia cells. Researchers are excited because this method could lead to more targeted and efficient destruction of cancer cells, with potentially fewer side effects than traditional therapies.

What evidence suggests that this treatment might be an effective treatment for leukemia?

Research shows that a special type of immune cell, called natural killer (NK) cells, can help fight acute myeloid leukemia (AML), especially when the disease returns or doesn't respond to treatment. These NK cells attack cancer cells, and when expanded using a substance called IL-21, they may become even more effective. In this trial, participants will receive IL-21-expanded NK cells as part of the induction treatment arm. Studies have found that these enhanced NK cells are safe for patients with AML who have a poor outlook. Additionally, these modified NK cells have shown effectiveness in lab tests on leukemia and other cancers. Early results suggest that this treatment could lower the chances of leukemia returning. ^{1 2 4 6 7}

Who Is on the Research Team?

Sumithira Vasu, MBBS

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with recurrent or treatment-resistant acute myeloid leukemia (AML) who weigh at least 42 kg, have a decent heart function and performance status, controlled seizures if present, acceptable liver and kidney functions, no active graft-versus-host disease or uncontrolled infections. They must not be on high-dose steroids or have had recent investigational therapies.

Inclusion Criteria

Patient weight ≥ 42 kg

Patients on hydrocortisone for adrenal insufficiency or on inhaled or topical steroids are eligible

Primary Relapsed AML including Relapsed AML after allogeneic stem cells

Exclusion Criteria

Any comorbidities that in the opinion of the investigator will preclude receiving fludarabine or cytarabine

Active GVHD

Prednisone dose is > 20 mg/day or >0.25mg/kg, whichever is higher will be excluded

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive fludarabine and cytarabine, followed by six doses of NK cells

3 weeks

Multiple visits for infusions

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Regular monitoring visits

What Are the Treatments Tested in This Trial?

Interventions

• Membrane-bound Interleukin-21-Expanded Haploidentical Natural Killer Cells

Trial Overview The trial is testing the safety of donor natural killer (NK) cells that are expanded using membrane-bound Interleukin-21 to treat AML. These genetically modified NK cells may help the immune system stop cancer growth and spread.

How Is the Trial Designed?

Group I: Induction Experimental Treatment 1 Intervention

Six doses of third-party-donor mbIL-21 expanded (KDS-1001) cells given thrice weekly for two weeks. Days may vary and KDS-1001 can be given from days 0 to 21

Group II: Conditioning Regimen Experimental Treatment 2 Interventions

Fludarabine 30 mg/m2/day (day -6 to day -2) and Cytarabine 2g/ m2/day (days -6 to day -2)

Who Is Running the Clinical Trial?

Sumithira Vasu

Lead Sponsor

Trials

6

Recruited

140+

Kiadis Pharma

Industry Sponsor

Trials

12

Recruited

540+

Published Research Related to This Trial

The phase 1 study involving 7 patients with refractory/relapsed acute myeloid leukemia (AML) demonstrated that adoptive transfer of activated NK cells (aNK) is safe, with no dose-limiting toxicities or severe adverse effects observed during treatment or the 21-day follow-up period.

While the aNK cell therapy showed transient activity in 3 out of 7 patients, the study confirmed the feasibility of using 'off-the-shelf' aNK cells, paving the way for future combination immunotherapy trials to enhance treatment for AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 clinical trial of adoptive immunotherapy using "off-the-shelf" activated natural killer cells in patients with refractory and relapsed acute myeloid leukemia. Boyiadzis, M., Agha, M., Redner, RL., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9582588/

Evaluation of allogeneic and autologous membrane-bound ... The contribution of ADCC to therapeutic antibody efficacy suggests a role for natural killer (NK) cells and other innate immune cells in CLL treatment.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02809092

Interleukin-21 (IL-21)- Expanded Natural Killer Cells for ... Human leukocyte antigen (HLA) haploidentical, Natural killer (NK) enriched peripheral blood cell infusions have shown safety in patients with poor prognosis AML ...

3. nature.com nature.com/articles/s41598-019-51287-6

Membrane bound IL-21 based NK cell feeder cells drive ... Inhibiting TGF-beta signaling preserves the function of highly activated, in vitro expanded natural killer cells in AML and colon cancer models.

4. ashpublications.org ashpublications.org/blood/article-abstract/130/16/1857/36493

Phase 1 clinical trial using mbIL21 ex vivo–expanded donor ... To test the hypothesis that natural killer (NK) cells can decrease the risk of leukemia relapse, we initiated a phase 1 dose-escalation study of membrane-bound ...

5. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0030264

Membrane-Bound IL-21 Promotes Sustained Ex Vivo ... Membrane-Bound IL-21 Promotes Sustained Ex Vivo Proliferation of Human Natural Killer Cells · We developed aAPCs for expansion of antigen-specific T cells by ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28835441/

Phase 1 clinical trial using mbIL21 ex vivo-expanded donor ... To test the hypothesis that natural killer (NK) cells can decrease the risk of leukemia relapse, we initiated a phase 1 dose-escalation study of ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01787474

Study Details | NCT01787474 | Donor Natural Killer Cells ... Determine the safety, feasibility, and maximum tolerated dose of membrane-bound interleukin 21 (mbIL21)-expanded haploidentical natural killer (NK) cells after ...