Allogeneic Stem Cell Transplant RecipientPhase 1NCT04220684
Trial Testing Safety of IL-21 NK Cells for Induction of R/R AML
A Phase 1 study testing Cytarabine Hydrochloride, Fludarabine and Membrane-bound Interleukin-21-Expanded Haploidentical Natural Killer Cells in people with Allogeneic Stem Cell Transplant Recipient and Blasts 10 Percent or More of Bone Marrow Nucleated Cells, run by Sumithira Vasu at 2 sites in United States.
Trial summary
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 (recurrent) or has not responded to treatment (refractory). Natural killer cells are a type of immune cell. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Allogeneic Stem Cell Transplant Recipient, Blasts 10 Percent or More of Bone Marrow Nucleated Cells, Recurrent Acute Myeloid Leukemia
- What is being tested?
- Cytarabine Hydrochloride, Fludarabine and Membrane-bound Interleukin-21-Expanded Haploidentical Natural Killer Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 2 sitesUnited States
- Study dates
- 11 Jun 2020to 22 Oct 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient Inclusion Criteria for Induction Phase
- Primary Relapsed AML including
- Relapsed AML after allogeneic stem cells
- Isolated CNS or extramedullary disease (Note: a response monitoring plan must be developed a priori for subjects with extramedullary disease)
- 1-3 prior lines of therapy which includes chemotherapy, hypomethylating agents, venetoclax or targeted therapy.
- Patient weight ≥ 42 kg
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- Performance status: Karnofsky or Lansky Performance Scale (PS) greater or equal to 70, or, ECOG score 0-2.
- Renal function: Serum creatinine ≤ 2 mg/dl and/or creatinine clearance greater or equal than 40 cc/min.
- Pulmonary function: FEV1, FVC and DLCO ≥ 50% of expected, corrected for hemoglobin.
- Liver function: Total bilirubin ≤ 2 mg/dl or ≤ 2.5 x ULN for age (unless Gilbert's syndrome) and SGPT (ALT) ≤ 2.5 x ULN for age.
- Cardiac function: left ventricular ejection fraction ≥ 40%.
- CNS: Patients with seizure disorder are eligible if seizures well controlled.
- Negative serum test to rule out pregnancy within 2 weeks prior to enrollment in females of childbearing potential (non-childbearing potential defined as premenarchal, greater than one year post-menopausal, or surgically sterilized).
- Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the Investigator.
- Ability to understand and willingness to sign the written informed consent document.
- Negative serology for human immunodeficiency virus (HIV).
- Patients on hydrocortisone for adrenal insufficiency or on inhaled or topical steroids are eligible.
- Maintenance Phase: Patients that complete induction therapy and who achieve a CR/CRi/PR within the designated follow-up period and who are ineligible, unable or unwilling to undergo HSCT; these patients will not receive fludarabine or cytarabine.
Who cannot join
- Investigational therapies in the 3 weeks prior to beginning treatment on this protocol.
- Patients receiving any concurrent therapy including but not limited to chemotherapy, targeted therapy, radiation therapy, or immunotherapy for R/R AML.
- Any comorbidities that in the opinion of the investigator will preclude receiving fludarabine or cytarabine.
- Uncontrolled infection, defined as an infection which has not resolved spontaneously or does not show evidence of significant resolution after initiating appropriate therapy. Asymptomatic viremia such as CMV, HPV, BK virus, HCV, HBV etc. is NOT considered as an exclusion criteria.
- Uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease.
- Active GVHD
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- Prednisone dose is > 20 mg/day or >0.25mg/kg, whichever is higher will be excluded.
- Patients with donor-specific antibodies with MFI > 5000 will be ineligible
- Maintenance Phase: Patients must continue to meet exclusion criteria as defined in Section 4.4.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Oregon Health & Science University
Portland, Oregon, 24344
About this study
Official title: A Phase I Clinical Trial Testing the Safety of IL-21-Expanded, Off-the-shelf, Third-party Natural Killer Cells (KDS-1001) for the Induction of Relapsed/Refractory Acute Myeloid Leukemia
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 (recurrent) or has not responded to treatment (refractory). Natural killer cells are a type of immune cell. Immunotherapy with genetically modified NK cells from donors may induce changes in the body's immune system and may interfere with the ability of cancer cells to grow and spread.
Read the detailed description
PRIMARY OBJECTIVE:
- To determine the safety of adoptive NK cell therapy using membrane-bound interleukin-21 (mbIL21)-expanded, off-the-shelf, third-party donor-derived NK cells in patients with relapsed/refractory acute myeloid leukemia (AML).
SECONDARY OBJECTIVES:
- Estimate the complete response (CR, CR with incomplete hematologic recovery [CRi] \& morphologic leukemia-free state [MLFS]).
II. Estimate the median relapse free survival. III. Estimate the median time to neutrophil and platelet count recovery. IV. Estimate the median duration of remission. V. Estimate the incidence of infectious complications. VI. Estimate percentage of patients receiving this regimen who are rendered transplant-eligible.
CORRELATIVE OBJECTIVES:
- Determine the persistence of ex-vivo expanded, off-the-shelf, third-party NK cells.
II. Characterize in vivo expansion of third-party NK cells and if it differs based on the conditioning regimen as defined by NK chimerism assay.
III. Determine the immunophenotype and function of expanded cells. IV. Chimerism analysis in patients who have had post-transplant relapses.
OUTLINE: This is a dose-escalation study of membrane-bound interleukin-21-expanded haploidentical natural killer cells.
INDUCTION: Patients receive fludarabine intravenously (IV) and cytarabine IV on days -6 to -2 in the absence of disease progression or unacceptable toxicity.
COHORT II: Patients who are >= 60 years old, unable/unwilling to tolerate intensive chemotherapy, or disease insensitive to cytarabine (tp53, TET2 mutations) receive fludarabine IV on days -5 to -2 and decitabine IV on days -6 to -2 in the absence of disease progression or unacceptable toxicity.
All patients receive membrane-bound interleukin-21-expanded haploidentical natural killer cells via infusion on days 0, 2, 4, 7, 9, and 11.
After completion of study treatment, patients are followed up to day 56.
- Conditions
- Allogeneic Stem Cell Transplant Recipient, Blasts 10 Percent or More of Bone Marrow Nucleated Cells, Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
- Being tested
- Cytarabine Hydrochloride, Fludarabine, Membrane-bound Interleukin-21-Expanded Haploidentical Natural Killer Cells
- Keywords
- Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cytarabine HydrochlorideDrug
Also called Ara-C HCl, Arabinosylcytosine Hydrochloride, Aracytidine Hydrochloride, CHX-3311
Given IV
FludarabineDrug
Also called Fluradosa
Given IV
Membrane-bound Interleukin-21-Expanded Haploidentical Natural Killer CellsBiological
Also called (mbIL21)-expanded Haploidentical NK Cells, Donor mbIL21-expanded NK Cells, mbIL21-expanded Haploidentical NK Cells
Given via infusion
| Study group | Role | What they receive |
|---|---|---|
| Conditioning Regimen | Experimental | Fludarabine 30 mg/m2/day (day -6 to day -2) and Cytarabine 2g/ m2/day (days -6 to day -2) Receives: Drug: Cytarabine Hydrochloride; Drug: Fludarabine |
| Induction | Experimental | 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 Receives: Biological: Membrane-bound Interleukin-21-Expanded Haploidentical Natural Killer Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) of membrane-bound interleukin-21-expanded haploidentical natural killer (NK) cells
The MTD will be defined as the highest safely tolerated dose where at most one patient in six experiences dose-limiting toxicity (DLT) during DLT observation period. DLT is defined as any steroid refractory acute graft versus host disease.
Measured: Up to 63 days
Incidence of adverse events
Toxicities will be assessed by type and grade using Common Terminology Criteria for Adverse Events version 5.0 and displayed in summary form by cohort and overall. Toxicities will be summarized and reported regardless of attribution and also only those attributed to NK cells.
Measured: Up to day 28
Secondary outcomes (8)
Complete response (CR)
Response rate with a 95% confidence interval (CI) will be reported for all evaluable patients, assuming a binomial distribution. Response rate will also be reported for those who received all 6 doses of NK cells.
Measured: Up to day 56
CR with incomplete hematologic recovery
Response rate with a 95% CI will be reported for all evaluable patients, assuming a binomial distribution. Response rate will also be reported for those who received all 6 doses of NK cells.
Measured: Up to day 56
Morphologic leukemia-free state
Response rate with a 95% CI will be reported for all evaluable patients, assuming a binomial distribution. Response rate will also be reported for those who received all 6 doses of NK cells.
Measured: Up to day 56
Median relapse free survival
Will use descriptive statistics to summarize the demographic and clinical characteristics of the patients on this study.
Measured: Up to day 56
Median time to neutrophil and platelet count recovery
Will use descriptive statistics to summarize the demographic and clinical characteristics of the patients on this study.
Measured: Up to day 56
Median duration of remission
Will use descriptive statistics to summarize the demographic and clinical characteristics of the patients on this study.
Measured: Up to day 56
Incidence of infectious complications
Will use descriptive statistics to summarize the demographic and clinical characteristics of the patients on this study.
Measured: Up to day 56
Percentage of patients receiving the regimen who are rendered transplant-eligible
Will use descriptive statistics to summarize the demographic and clinical characteristics of the patients on this study.
Measured: Up to day 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2020
- Study start11 Jun 2020
- Primary completion22 Oct 2024
- Study completion22 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Allogeneic Stem Cell Transplant RecipientStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sumithira Vasu
- Sponsor type
- University, hospital or other
- Collaborators
- Kiadis Pharma
- Responsible party
- Sponsor-investigator, Sumithira Vasu, Ohio State University Comprehensive Cancer Center
- Investigators
- Sumithira Vasu, MBBS, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04220684
- Sponsor's protocol ID
- OSU-18336
- Other IDs
- NCI-2019-05150
- Status last verified
- Jan 2026
- First submitted
- 26 Sep 2019
- Last updated
- 9 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Clinical Trial Testing the Safety of IL-21-Expanded, Off-the-shelf, Third-party Natural Killer Cells (KDS-1001) for the Induction of Relapsed/Refractory Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT04220684
- Acronym / sponsor ID
- OSU-18336
- Conditions
- Allogeneic Stem Cell Transplant Recipient, Blasts 10 Percent or More of Bone Marrow Nucleated Cells, Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
- Keywords
- Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Sumithira VasuUniversity, hospital or other
- Collaborators
- Kiadis Pharma
- Study start
- 11 Jun 2020 (actual)
- Primary completion
- 22 Oct 2024 (actual)
- Study completion
- 22 Oct 2024 (actual)
- First posted
- 7 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 (recurrent) or has not responded to treatment (refractory). Natural killer cells are a type of immune cell. Immunotherapy with genetically modified NK cells from donors may induce changes in the body's immune system and may interfere with the ability of cancer cells to grow and spread.
Detailed description
PRIMARY OBJECTIVE:
- To determine the safety of adoptive NK cell therapy using membrane-bound interleukin-21 (mbIL21)-expanded, off-the-shelf, third-party donor-derived NK cells in patients with relapsed/refractory acute myeloid leukemia (AML).
SECONDARY OBJECTIVES:
- Estimate the complete response (CR, CR with incomplete hematologic recovery [CRi] \& morphologic leukemia-free state [MLFS]).
II. Estimate the median relapse free survival. III. Estimate the median time to neutrophil and platelet count recovery. IV. Estimate the median duration of remission. V. Estimate the incidence of infectious complications. VI. Estimate percentage of patients receiving this regimen who are rendered transplant-eligible.
CORRELATIVE OBJECTIVES:
- Determine the persistence of ex-vivo expanded, off-the-shelf, third-party NK cells.
II. Characterize in vivo expansion of third-party NK cells and if it differs based on the conditioning regimen as defined by NK chimerism assay.
III. Determine the immunophenotype and function of expanded cells. IV. Chimerism analysis in patients who have had post-transplant relapses.
OUTLINE: This is a dose-escalation study of membrane-bound interleukin-21-expanded haploidentical natural killer cells.
INDUCTION: Patients receive fludarabine intravenously (IV) and cytarabine IV on days -6 to -2 in the absence of disease progression or unacceptable toxicity.
COHORT II: Patients who are >= 60 years old, unable/unwilling to tolerate intensive chemotherapy, or disease insensitive to cytarabine (tp53, TET2 mutations) receive fludarabine IV on days -5 to -2 and decitabine IV on days -6 to -2 in the absence of disease progression or unacceptable toxicity.
All patients receive membrane-bound interleukin-21-expanded haploidentical natural killer cells via infusion on days 0, 2, 4, 7, 9, and 11.
After completion of study treatment, patients are followed up to day 56.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Conditioning Regimen | Experimental | Drug: Cytarabine Hydrochloride, Drug: FludarabineFludarabine 30 mg/m2/day (day -6 to day -2) and Cytarabine 2g/ m2/day (days -6 to day -2) |
| Induction | Experimental | Biological: Membrane-bound Interleukin-21-Expanded Haploidentical Natural Killer CellsSix 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patient Inclusion Criteria for Induction Phase
- Primary Relapsed AML including
- Relapsed AML after allogeneic stem cells
- Isolated CNS or extramedullary disease (Note: a response monitoring plan must be developed a priori for subjects with extramedullary disease)
- 1-3 prior lines of therapy which includes chemotherapy, hypomethylating agents, venetoclax or targeted therapy.
Key exclusion criteria (9 listed)
- Investigational therapies in the 3 weeks prior to beginning treatment on this protocol.
- Patients receiving any concurrent therapy including but not limited to chemotherapy, targeted therapy, radiation therapy, or immunotherapy for R/R AML.
- Any comorbidities that in the opinion of the investigator will preclude receiving fludarabine or cytarabine.
- Uncontrolled infection, defined as an infection which has not resolved spontaneously or does not show evidence of significant resolution after initiating appropriate therapy. Asymptomatic viremia such as CMV, HPV, BK virus, HCV, HBV etc. is NOT considered as an exclusion criteria.
- Uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cytarabine HydrochlorideAlso: Ara-C HCl, Arabinosylcytosine Hydrochloride, Aracytidine Hydrochloride, CHX-3311Given IV | Drug | Conditioning Regimen |
| FludarabineAlso: FluradosaGiven IV | Drug | Conditioning Regimen |
| Membrane-bound Interleukin-21-Expanded Haploidentical Natural Killer CellsAlso: (mbIL21)-expanded Haploidentical NK Cells, Donor mbIL21-expanded NK Cells, mbIL21-expanded Haploidentical NK CellsGiven via infusion | Biological | Induction |
Primary outcome
Maximum tolerated dose (MTD) of membrane-bound interleukin-21-expanded haploidentical natural killer (NK) cells
Time frame: Up to 63 days
The MTD will be defined as the highest safely tolerated dose where at most one patient in six experiences dose-limiting toxicity (DLT) during DLT observation period. DLT is defined as any steroid refractory acute graft versus host disease.
Incidence of adverse events
Time frame: Up to day 28
Toxicities will be assessed by type and grade using Common Terminology Criteria for Adverse Events version 5.0 and displayed in summary form by cohort and overall. Toxicities will be summarized and reported regardless of attribution and also only those attributed to NK cells.
8 secondary outcomes
Complete response (CR)
Time frame: Up to day 56
CR with incomplete hematologic recovery
Time frame: Up to day 56
Morphologic leukemia-free state
Time frame: Up to day 56
Median relapse free survival
Time frame: Up to day 56
Median time to neutrophil and platelet count recovery
Time frame: Up to day 56
Median duration of remission
Time frame: Up to day 56
Incidence of infectious complications
Time frame: Up to day 56
Percentage of patients receiving the regimen who are rendered transplant-eligible
Time frame: Up to day 56
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2026.
- The JameslineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sumithira Vasu, MBBS principal investigator
Ohio State University Comprehensive Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cytarabine Hydrochloride, Fludarabine and Membrane-bound Interleukin-21-Expanded Haploidentical Natural Killer Cells in people with Allogeneic Stem Cell Transplant Recipient and Blasts 10 Percent or More of Bone Marrow Nucleated Cells, run by Sumithira Vasu at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) of membrane-bound interleukin-21-expanded haploidentical natural killer (NK) cells (time frame: Up to 63 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2026.