NK Cells + SCT for Leukemia

Overseen By Jeremy Ramdial, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Systemic corticosteroids

Disqualifiers: HIV, Hepatitis B/C, Liver cirrhosis, 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 explores the safety and effectiveness of KDS-1001, a new treatment using natural killer (NK) cells from a donor, combined with a standard stem cell transplant for leukemia. It targets patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myeloid leukemia (CML). The trial includes multiple treatment components, such as medications and therapies like cyclophosphamide and total body irradiation, to enhance outcomes and reduce complications. Individuals with specific forms of these blood cancers who have not responded well to prior treatments might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids with a prednisone dose greater than 10 mg, you may not be eligible to participate.

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

Research shows that KDS-1001, which uses special immune cells from a donor, has been tested for safety in people with leukemia. Earlier studies have generally found these immune cells to be well-tolerated. Most patients experienced only mild to moderate side effects, such as flu-like symptoms, including fever and chills, which are common with treatments involving immune cells.

Although KDS-1001 remains under investigation, its presence in later research stages suggests some confidence in its safety. Studies indicate that side effects are manageable, but individual experiences can vary. Always discuss potential risks and benefits with the trial team before joining. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores a novel combination of natural killer (NK) cells and stem cell transplantation (SCT) for treating leukemia. Unlike traditional chemotherapy or radiation, this approach harnesses the body's own immune system to target cancer cells more precisely. The use of NK cells is particularly promising because they can seek out and destroy cancer cells without harming healthy cells, potentially reducing side effects. This innovative strategy aims to improve outcomes by lowering the risk of graft-versus-host disease (GVHD), a common complication of SCT, with the help of cyclophosphamide and tacrolimus. By integrating these treatments, the trial has the potential to offer a more effective and targeted option for leukemia patients.

What evidence suggests that this trial's treatments could be effective for leukemia?

Research has shown that natural killer (NK) cells, like those in KDS-1001, can help fight leukemia by identifying and destroying cancer cells. In past treatments, patients with acute myeloid leukemia (AML) who received NK cells experienced promising outcomes, with a reduced chance of cancer recurrence after treatment. This trial will evaluate KDS-1001 in combination with stem cell transplants (SCT). Studies have found that using NK cells with SCT can improve transplant success, reduce the risk of graft-versus-host disease (GVHD), and help prevent cancer recurrence. These findings suggest that KDS-1001, when combined with SCT, could effectively treat AML, myelodysplastic syndrome (MDS), or chronic myeloid leukemia (CML). ^{1 5 6 7 8}

Who Is on the Research Team?

Jeremy Ramdial, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults aged 18-70 with certain myeloid malignancies (AML, MDS, CML) who have a compatible stem cell donor. They must weigh at least 42 kg and have good heart and lung function, as well as adequate liver and kidney function. Excluded are those with CNS involvement of cancer within the last 3 months, other active cancers (except nonmelanoma skin cancer), uncontrolled infections, or severe allergies to trial substances.

Inclusion Criteria

Patients weighing at least 42 kg

Sexually active individuals must agree to use contraception

My MDS is classified as intermediate or high-risk.

Exclusion Criteria

I am on a daily dose of more than 10 mg of prednisone or similar steroids.

I am not pregnant.

Known history of allergic reactions to product constituents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Participants receive conditioning regimen including melphalan, fludarabine, and total body irradiation

7 days

Daily visits for administration

Stem Cell Transplantation and NK Cell Administration

Participants receive stem cell transplantation and NK cell administration

1 day

Inpatient stay for transplantation

Post-transplant Treatment

Participants receive post-transplant medications including cyclophosphamide, mesna, mycophenolate mofetil, and tacrolimus

90 days

Regular visits for monitoring and medication administration

Follow-up

Participants are monitored for safety, effectiveness, and complications such as GVHD and infections

1 year

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• KDS-1001

Trial Overview The trial is testing the safety and effectiveness of KDS-1001 natural killer cells combined with standard stem cell transplant in treating acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myeloid leukemia (CML). The NK cells are from a third-party donor.

How Is the Trial Designed?

Group I: Total Body Irradiation One Dose Experimental Treatment 1 Intervention

on Day -2, you may receive 1 dose of total body irradiation (TBI).

Group II: Tacrolimus Experimental Treatment 1 Intervention

Starting on Day 5, you will begin receiving tacrolimus to help lower the risk of GVHD. You will begin by receiving it nonstop by vein until you are able to take it by mouth. You will then take tacrolimus by mouth 2 times a day for about 3 months.

Group III: Mycophenolate mofetil Experimental Treatment 1 Intervention

by mouth 3 times a day for 90 days or longer.

Group IV: Mesna Experimental Treatment 1 Intervention

On Days 3 and 4, You will also receive mesna by vein over 30 minutes every 4 hours for a total of 10 mesna doses.

Group V: Melphalan Experimental Treatment 1 Intervention

On Day -7, you will receive melphalan by vein over about 30 minutes.

Group VI: Fludarabine phosphate Experimental Treatment 1 Intervention

On Days -7, -6, -5, and -4, you will receive fludarabine by vein about 1 hour.

Group VII: Filgrastim Experimental Treatment 1 Intervention

Starting on Day 7, you will begin to receive filgrastim as an injection under the skin 1 time a day.

Group VIII: Cyclophosphamide Experimental Treatment 1 Intervention

On Days 3 and 4, you will receive cyclophosphamide by vein over about 3 hours to help lower the risk of graft-versus-host disease

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

In a study of 10 patients with acute myeloid leukemia (AML) who received haploidentical stem-cell transplants, no graft versus leukemia (GvL) effect was observed, indicating a potential issue with NK cell recovery and function post-transplant.

The NK cells from these patients exhibited an immature phenotype with reduced cytotoxicity, which was linked to increased expression of CD94/NKG2A; blocking this receptor improved their ability to kill AML cells, suggesting a mechanism that could be targeted to enhance immune responses after transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NK-cell reconstitution after haploidentical hematopoietic stem-cell transplantations: immaturity of NK cells and inhibitory effect of NKG2A override GvL effect. Nguyen, S., Dhedin, N., Vernant, JP., et al.[2021]

In a study of 80 pediatric acute leukemia patients who underwent αβT/B-depleted haplo-HSCT, the presence of alloreactive NK cells significantly contributed to the graft-versus-leukemia effect, enhancing anti-leukemia activity.

The study found that while HCMV reactivation influenced the differentiation of NK cells, there was no significant correlation between the differentiated NK cell phenotype and relapse-free survival, suggesting that other factors may also play a role in patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phenotypic and Functional Characterization of NK Cells in αβT-Cell and B-Cell Depleted Haplo-HSCT to Cure Pediatric Patients with Acute Leukemia. Meazza, R., Falco, M., Loiacono, F., et al.[2020]

The study involved 7 pediatric patients with acute myeloid leukemia (AML) who received activated and expanded natural killer (NK) cells as a treatment after chemotherapy, showing that this approach is safe and feasible.

After a median follow-up of 33 months, 85.7% of patients remained in complete remission, and the 3-year overall survival rate was 83.3%, although the small sample size limits definitive conclusions about efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 Clinical Trial of Infusing Haploidentical K562-mb15-41BBL-Activated and Expanded Natural Killer Cells as Consolidation Therapy for Pediatric Acute Myeloblastic Leukemia. Gómez García, LM., Escudero, A., Mestre, C., et al.[2022]

In a phase 1 trial involving 9 pediatric and young adult patients with relapsed acute myeloid leukemia (AML) after hematopoietic cell transplantation, donor-derived memory-like natural killer (ML NK) cells showed significant antileukemic activity, leading to complete remission in 4 out of 8 evaluable patients by day 28.

The ML NK cells expanded and persisted for over 3 months without significant toxicity, suggesting that this approach, combined with donor lymphocyte infusions, could be a promising new immunotherapy for relapsed AML in a post-transplant setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donor memory-like NK cells persist and induce remissions in pediatric patients with relapsed AML after transplant. Bednarski, JJ., Zimmerman, C., Berrien-Elliott, MM., et al.[2023]

In a study testing CD33-CAR NK cells in patients with relapsed and refractory acute myeloid leukemia (AML), no significant adverse effects were observed at doses up to 5 billion cells per patient, suggesting a favorable safety profile.

CAR NK-92 cells can be produced at a lower cost than CAR T cells, indicating that with further optimization, they could become a more accessible treatment option for cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-man clinical trial of CAR NK-92 cells: safety test of CD33-CAR NK-92 cells in patients with relapsed and refractory acute myeloid leukemia. Tang, X., Yang, L., Li, Z., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04808115

NCT04808115 | IIT PH1 KDS-1001 in Patients With CML This open label, non-randomized, prospective phase I study is designed to evaluate if the addition of natural killer cell therapy (KDS-1001) to tyrosine kinase ...

2. trial.medpath.com trial.medpath.com/clinical-trial/8ff6830407293f86/off-the-shelf-nk-cell-allogeneic-sct-myeloid-malignancies

Off-the-shelf NK Cells + SCT for Myeloid Malignancies The goal of this clinical research study is to learn about the safety and effectiveness of giving KDS-1001 in combination with a standard stem cell transplant ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04220684

NCT04220684 | Trial Testing Safety of IL-21 NK Cells for ... This phase I trial studies the side effects of donor natural killer (NK) cell therapy in treating patients with acute myeloid leukemia that has come back ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2019-05150

NK cells (KDS-1001) in Treating Patients with Recurrent or ... This phase I trial studies the best dose and safety of KDS-1001 to see how well it works in treating patients with acute myeloid leukemia that has come back ...

5. researchgate.net researchgate.net/publication/386471417_Phase_II_Clinical_Trial_of_Off-the-Shelf_NK_Cells_with_Allogeneic_Stem_Cell_Transplantation_in_Patients_with_High-Risk_Myeloid_Malignancies

Phase II Clinical Trial of “Off-the-Shelf” NK Cells with Allogeneic ... Alloreactive NK cells have been reported to enhance engraftment, reduce GVHD and prevent relapse of leukemia post transplant in both preclinical and clinical ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4841/533278/Phase-II-Clinical-Trial-of-Off-the-Shelf-NK-Cells

Phase II Clinical Trial of “Off-the-Shelf” NK Cells with ... KDS-1001 is composed of NK cells from an allogeneic third party donor, expanded ex vivo using PM21 membrane particles, which are formed from ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04220684

Trial Testing Safety of IL-21 NK Cells for Induction of R/R AML This phase I trial studies the side effects of donor natural killer (NK) cell therapy in treating patients with acute myeloid leukemia that has come back ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124075992

Phase II Clinical Trial of “Off-the-Shelf” NK Cells with ... KDS-1001 is composed of NK cells from an allogeneic third party donor, expanded ex vivo using PM21 membrane particles, which are formed from ...