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

24 Participants Needed

Trial Summary

What is the purpose of this trial?

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 to patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myeloid leukemia (CML). KDS-1001 is a study product created using certain immune cells called natural killer (NK) cells collected from a third-party donor.

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.

What data supports the effectiveness of the treatment KDS-1001 in the clinical trial NK Cells + SCT for Leukemia?

Research shows that natural killer (NK) cell therapy has been effective in treating blood cancers, including leukemia, by boosting the body's immune response against cancer cells. Although NK cell therapy alone did not significantly improve survival rates in some studies, it has shown promise when combined with other treatments, suggesting potential benefits in the context of stem cell transplantation. ^{1 2 3 4 5}

Is the NK Cells + SCT treatment generally safe for humans?

Research shows that NK cell treatments, including those similar to KDS-1001, have been tested in various clinical trials and are generally safe for humans. These studies reported no significant adverse effects, and patients tolerated the treatments well, with some experiencing mild side effects like low-grade graft-versus-host disease (a condition where donor cells attack the recipient's body). ^{6 7 8 9 10}

What makes the NK Cells + SCT treatment for leukemia unique?

This treatment is unique because it uses natural killer (NK) cells, which are a type of immune cell that can target and destroy leukemia cells, especially when combined with stem cell transplantation (SCT). The NK cells are selected or activated to be alloreactive, meaning they can specifically recognize and attack leukemia cells without harming healthy cells, offering a targeted approach to treatment. ^{11 12 13 14 15}

Research Team

Jeremy Ramdial, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

A phase II clinical trial of adoptive transfer of haploidentical natural killer cells for consolidation therapy of pediatric acute myeloid leukemia. [2020]

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

Recent progress in and challenges in cellular therapy using NK cells for hematological malignancies. [2021]

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

Natural killer cell therapy for hematologic malignancies: successes, challenges, and the future. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

iPSC-Derived Natural Killer Cell Therapies - Expansion and Targeting. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Long-Term Outcome After Adoptive Immunotherapy With Natural Killer Cells: Alloreactive NK Cell Dose Still Matters. [2022]

6. United States 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. [2022]

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

Phase 1 clinical trial using mbIL21 ex vivo-expanded donor-derived NK cells after haploidentical transplantation. [2021]

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

Donor memory-like NK cells persist and induce remissions in pediatric patients with relapsed AML after transplant. [2023]

9. United States 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. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Decrease post-transplant relapse using donor-derived expanded NK-cells. [2022]

11. United States 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. [2021]

12. Egypt pubmed.ncbi.nlm.nih.gov

High-Risk Leukemia: Past, Present, and Future Role of NK Cells. [2018]

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

Anti-leukemia activity of alloreactive NK cells in KIR ligand-mismatched haploidentical HSCT for pediatric patients: evaluation of the functional role of activating KIR and redefinition of inhibitory KIR specificity. [2021]

14. Italy pubmed.ncbi.nlm.nih.gov

Human acute myeloid leukemia CD34+CD38- stem cells are susceptible to allorecognition and lysis by single KIR-expressing natural killer cells. [2021]

15. Switzerland 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. [2020]