Acute Myeloid LeukemiaPhase 1/2KARMANCT05503134
Safety and Efficacy of Expanded, Universal Donor Natural Killer Cells for Relapsed/Refractory AML
A Phase 1/2 study testing Universal Donor Natural Killer Cells in people with Acute Myeloid Leukemia, run by Nationwide Children's Hospital at 1 site in United States.
Trial summary
This is a phase I/II dose escalation study designed to determine the safety and estimate the efficacy of UD-NK cells combined with FLA chemotherapy in patients age 1-24.99 with relapsed or refractory acute myeloid leukemia. PRIMARY OBJECTIVE: I. Read more about this study
- Who is it for?
- Ages 1 year to 24 years
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Universal Donor Natural Killer Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Feb 2022to Feb 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 1 year to 24 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients with relapsed or primary refractory AML, including:
- Patients with relapsed AML (Any patient in first or subsequent relapse are eligible. Patients with relapse after HSCT are eligible)
- Primary refractory AML defined as failure to achieve a complete response after 2 cycles of induction chemotherapy, including persistent MRD positivity
- Patients with isolated CNS or extramedullary disease are eligible Note: a response monitoring plan must be developed a priori for subjects with extramedullary disease
- Patient age 1-24.99 years old
- Negative serum test to rule out pregnancy within 2 weeks prior to enrollment in females of childbearing potential
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- o Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the Investigator for 6 months after the last dose of chemotherapy and/or NK cell infusion
- Negative serology for human immunodeficiency virus (HIV)
- Both males and females and members of all races and ethnic groups are eligible
- Organ function requirements:
- Renal function: Creatinine ≤ 2 mg/dl OR creatinine clearance > 60 ml/min/1.73m2.
- Liver function: Total bilirubin ≤ 2 mg/dl (unless Gilbert's syndrome), AST and ALT ≤ 5 times the upper limit of normal (unless related to leukemic involvement). Upper limit of normal should be determined by the institutional defined normal laboratory range.
- Cardiac function: left ventricular ejection fraction ≥ 40% or shortening fraction ≥20%. May be eligible after cardiology clearance if qualitatively normal function or repeat measures are normal.
- CNS: Patients with seizure disorder may be eligible if seizures well controlled
- All prior treatment related non-hematologic toxicities must have resolved to ≤ Grade 2 prior to enrollment unless granted approval by study PI and/or Co-Is.
- All patients and/or their legal guardians must be able to understand and willing to sign a written informed consent document
Who cannot join
- AML directed therapies in the 2 weeks prior to beginning treatment on this protocol (except for hydroxyurea)
- o Note: There is no waiting period required for patients having received intrathecal cytarabine, methotrexate and/or hydrocortisone
- Patients on immunosuppressive therapy
- o Patients must be off of all systemic immunosuppressive therapy for at least 2 weeks prior to enrollment with no evidence of recurrent GVHD
- Patients with a history of donor lymphocyte infusion or cellular therapy within the last 30 days are not eligible for this study
- Allogeneic SCT < 3 months prior to study enrollment
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- Any comorbidities that in the opinion of the investigator will preclude receiving study therapy
- Performance status: Karnofsky or Lansky Performance Scale (PS) < 50
- Uncontrolled infection, defined as an infection which has not resolved or does not show evidence of significant resolution after initiating appropriate therapy
- o Asymptomatic viremia such as CMV, HPV, BK virus, HCV, etc. is NOT considered as an exclusion criterion
- Uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease
- History of autoimmune disease
- Active GVHD at the time of enrollment
- Patients with a history of adoptive cell therapy are excluded unless at least 30 days from infusion and with evidence of recovery of normal hematopoiesis (ANC ≥ 500/μL, platelet count ≥ 50,000/μL).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Nationwide Children's Hospital
Columbus, Ohio, 43205
Melinda Triplet, 6147226039, melinda.triplet@nationwidechildrens.org
About this study
Official title: Killer Cells Against Relapsed/Refractory Myeloid Acute Leukemia (KARMA): a Clinical Trial Evaluating the Safety and Efficacy of Expanded, Universal Donor Natural Killer Cells for Treatment of Relapsed/Refractory Acute Myeloid Leukemia
This is a phase I/II dose escalation study designed to determine the safety and estimate the efficacy of UD-NK cells combined with FLA chemotherapy in patients age 1-24.99 with relapsed or refractory acute myeloid leukemia.
PRIMARY OBJECTIVE:
Read more
- To determine the safety and recommended phase II dose of adoptive NK cell therapy using UD-NK cells in pediatric and young adult patients with relapsed/refractory AML.
SECONDARY OBJECTIVES:
- To estimate the efficacy of UD- NK cells with FLA chemotherapy in pediatric and young adult patients with relapsed/refractory AML.
EXPLORATORY OBJECTIVES:
- To determine the immunophenotype and function of UD-NK cells
II. To characterize in vivo expansion of UD-NK cells
III. To determine the persistence of UD-NK cells
Six doses of universal donor mbIL-21 expanded NK cells (UD-NK) given thrice weekly for two weeks. Days may vary and NK cells can be given from days 0 to 21. Patients may receive up to 2 cycles of fludarabine/cytarabine (FLA) + NK cells (up to 12 NK cell infusions) if they do not achieve CR after cycle 1 or if necessary to bridge to transplant.
Read the detailed description
The treatment plan consists of Fludarabine/Cytarabine chemotherapy followed by six doses of universal donor mbIL-21 expanded NK cells (UD-NK) given thrice weekly for two weeks. Days may vary and NK cells can be given from days 0 to 21. Patients may receive up to 2 cycles of fludarabine/cytarabine (FLA) + NK cells (up to 12 NK cell infusions) if they do not achieve CR after cycle 1 or if necessary to bridge to transplant.
In this study the first NK cell infusion is referred as day zero (D0), treatment plan activities prior or after D0 are denominated as day minus (D-) or day plus (D+).
FLA will be give as follows: Fludarabine 30 mg/m2/day (day -6 to day -2) and Cytarabine 2000 mg/ m2/day (days -6 to day -2)
Six doses of UD-NK cells will be given thrice weekly for two weeks beginning day 0. NK cell administration schedule may vary and doses may be given from day 0 to 21. A minimum of 2 days between NK cell doses is required. Patients must meet eligibility criteria for NK cell infusion as described in the protocol.
Patients will be eligible to receive a second cycle of chemotherapy for the following reasons:
- <CR after cycle 1
- Additional cycle is needed to bridge the patient to HSCT
Criteria to begin Cycle 2:
- ≥28 days since the first NK Cell infusion
- ≥2 days since the last NK Cell infusion in cycle 1
- Bone marrow evaluation after cycle 1 complete
- It is suggested but not required for ANC > 500/uL AND platelets >50,000/uL prior to beginning cycle 2
- Prior treatment related toxicities must have resolved to ≤ Grade 2
NK Cell Dose Levels:
- Dose level 1: 1.00x10^7 NK cell/kg (±20%) each dose for 6 doses per cycle
- Dose level 2: 3.00x10^7 NK cell/kg (±20%) each dose for 6 doses per cycle
- Dose level 3: 1.00x10^8 NK cell/kg (±20%) each dose for 6 doses per cycle
The NK dose will be calculated based on actual body weight. Dose escalation will proceed according to the study design outlined in Section 9.1 to determine the MTD. Once a patient is enrolled at a dose level, the dose will remain at the enrolled dose level for all subsequent NK cell infusions.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Universal Donor Natural Killer Cells
- Keywords
- AML
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Universal Donor Natural Killer CellsBiological
Six doses of UD-NK cells will be given thrice weekly for two weeks for up to 2 cycles of treatment
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Fludarabine 30 mg/m2/day (day -6 to day -2) and Cytarabine 2000 mg/ m2/day (days -6 to day -2)
Six doses of universal donor IL-21 expanded NK cells (UD-NK) given thrice weekly for two weeks starting on day 0. Days may vary and NK cells can be given from days 0 to 21. Patients may receive up to 2 cycles of fludarabine/cytarabine (FLA) + NK cells (up to 12 NK cell infusions) if they do not achieve CR after cycle 1 or if necessary to bridge to transplant. Receives: Biological: Universal Donor Natural Killer Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of adverse events
Measured: Up to 56 days after the first NK cell infusion
Rate of dose limiting toxicities
Measured: Up to 56 days after the first NK cell infusion
Secondary outcomes (7)
Minimal Residual Disease (MRD) negative response rate by flow cytometry
Measured: At the end of Cycle 1 and Cycle 2 (each cycle is 28 days)
CR rate after first cycle
Measured: At the end of Cycle 1 (each cycle is 28 days)
Relapse free survival and overall survival
Measured: 1 year
Median time to neutrophil and platelet count recovery
Measured: 1 year
Median duration of remission for patients who do not go onto transplant
Measured: 1 year
Incidence of infectious complications
Measured: 1 year
Percentage of patients receiving this regimen who are rendered transplant-eligible
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2022
- Study start14 Feb 2022
- Primary completionFeb 2027 (estimated)
- Study completionFeb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Nationwide Children's HospitalThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nationwide Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Margaret Lamb, MD, Principal investigator, Nationwide Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05503134
- Sponsor's protocol ID
- KARMA
- Acronym
- KARMA
- Status last verified
- Oct 2024
- First submitted
- 14 Feb 2022
- Last updated
- 4 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: IPD would only be shared following publication of the study.
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Killer Cells Against Relapsed/Refractory Myeloid Acute Leukemia (KARMA): a Clinical Trial Evaluating the Safety and Efficacy of Expanded, Universal Donor Natural Killer Cells for Treatment of Relapsed/Refractory Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT05503134
- Acronym / sponsor ID
- KARMA / KARMA
- Conditions
- Acute Myeloid Leukemia
- Keywords
- AML
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Nationwide Children's HospitalUniversity, hospital or other
- Study start
- 14 Feb 2022 (actual)
- Primary completion
- Feb 2027 (estimated)
- Study completion
- Feb 2027 (estimated)
- First posted
- 16 Aug 2022 (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 is a phase I/II dose escalation study designed to determine the safety and estimate the efficacy of UD-NK cells combined with FLA chemotherapy in patients age 1-24.99 with relapsed or refractory acute myeloid leukemia.
PRIMARY OBJECTIVE:
- To determine the safety and recommended phase II dose of adoptive NK cell therapy using UD-NK cells in pediatric and young adult patients with relapsed/refractory AML.
SECONDARY OBJECTIVES:
- To estimate the efficacy of UD- NK cells with FLA chemotherapy in pediatric and young adult patients with relapsed/refractory AML.
EXPLORATORY OBJECTIVES:
- To determine the immunophenotype and function of UD-NK cells
II. To characterize in vivo expansion of UD-NK cells
III. To determine the persistence of UD-NK cells
Six doses of universal donor mbIL-21 expanded NK cells (UD-NK) given thrice weekly for two weeks. Days may vary and NK cells can be given from days 0 to 21. Patients may receive up to 2 cycles of fludarabine/cytarabine (FLA) + NK cells (up to 12 NK cell infusions) if they do not achieve CR after cycle 1 or if necessary to bridge to transplant.
Detailed description
The treatment plan consists of Fludarabine/Cytarabine chemotherapy followed by six doses of universal donor mbIL-21 expanded NK cells (UD-NK) given thrice weekly for two weeks. Days may vary and NK cells can be given from days 0 to 21. Patients may receive up to 2 cycles of fludarabine/cytarabine (FLA) + NK cells (up to 12 NK cell infusions) if they do not achieve CR after cycle 1 or if necessary to bridge to transplant.
In this study the first NK cell infusion is referred as day zero (D0), treatment plan activities prior or after D0 are denominated as day minus (D-) or day plus (D+).
FLA will be give as follows: Fludarabine 30 mg/m2/day (day -6 to day -2) and Cytarabine 2000 mg/ m2/day (days -6 to day -2)
Six doses of UD-NK cells will be given thrice weekly for two weeks beginning day 0. NK cell administration schedule may vary and doses may be given from day 0 to 21. A minimum of 2 days between NK cell doses is required. Patients must meet eligibility criteria for NK cell infusion as described in the protocol.
Patients will be eligible to receive a second cycle of chemotherapy for the following reasons:
- <CR after cycle 1
- Additional cycle is needed to bridge the patient to HSCT
Criteria to begin Cycle 2:
- ≥28 days since the first NK Cell infusion
- ≥2 days since the last NK Cell infusion in cycle 1
- Bone marrow evaluation after cycle 1 complete
- It is suggested but not required for ANC > 500/uL AND platelets >50,000/uL prior to beginning cycle 2
- Prior treatment related toxicities must have resolved to ≤ Grade 2
NK Cell Dose Levels:
- Dose level 1: 1.00x10^7 NK cell/kg (±20%) each dose for 6 doses per cycle
- Dose level 2: 3.00x10^7 NK cell/kg (±20%) each dose for 6 doses per cycle
- Dose level 3: 1.00x10^8 NK cell/kg (±20%) each dose for 6 doses per cycle
The NK dose will be calculated based on actual body weight. Dose escalation will proceed according to the study design outlined in Section 9.1 to determine the MTD. Once a patient is enrolled at a dose level, the dose will remain at the enrolled dose level for all subsequent NK cell infusions.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Biological: Universal Donor Natural Killer CellsFludarabine 30 mg/m2/day (day -6 to day -2) and Cytarabine 2000 mg/ m2/day (days -6 to day -2) Six doses of universal donor IL-21 expanded NK cells (UD-NK) given thrice weekly for two weeks starting on day 0. Days may vary and NK cells can be given from days 0 to 21. Patients may receive up to 2 cycles of fludarabine/cytarabine (FLA) + NK cells (up to 12 NK cell infusions) if they do not achieve CR after cycle 1 or if necessary to bridge to transplant. |
Who may qualify
- Ages
- 1 year to 24 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (16 listed)
- Patients with relapsed or primary refractory AML, including:
- Patient age 1-24.99 years old
- Negative serum test to rule out pregnancy within 2 weeks prior to enrollment in females of childbearing potential
- o Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the Investigator for 6 months after the last dose of chemotherapy and/or NK cell infusion
- Negative serology for human immunodeficiency virus (HIV)
Key exclusion criteria (14 listed)
- AML directed therapies in the 2 weeks prior to beginning treatment on this protocol (except for hydroxyurea)
- o Note: There is no waiting period required for patients having received intrathecal cytarabine, methotrexate and/or hydrocortisone
- Patients on immunosuppressive therapy
- o Patients must be off of all systemic immunosuppressive therapy for at least 2 weeks prior to enrollment with no evidence of recurrent GVHD
- Patients with a history of donor lymphocyte infusion or cellular therapy within the last 30 days are not eligible for this study
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 |
|---|---|---|
| Universal Donor Natural Killer CellsSix doses of UD-NK cells will be given thrice weekly for two weeks for up to 2 cycles of treatment | Biological | Treatment |
Primary outcome
Incidence and severity of adverse events
Time frame: Up to 56 days after the first NK cell infusion
Rate of dose limiting toxicities
Time frame: Up to 56 days after the first NK cell infusion
7 secondary outcomes
Minimal Residual Disease (MRD) negative response rate by flow cytometry
Time frame: At the end of Cycle 1 and Cycle 2 (each cycle is 28 days)
CR rate after first cycle
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Relapse free survival and overall survival
Time frame: 1 year
Median time to neutrophil and platelet count recovery
Time frame: 1 year
Median duration of remission for patients who do not go onto transplant
Time frame: 1 year
Incidence of infectious complications
Time frame: 1 year
Percentage of patients receiving this regimen who are rendered transplant-eligible
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2024.
- Individual participant dataSharing planned: Undecided. IPD would only be shared following publication of the study.
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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.
Margaret Lamb, MD principal investigator
Nationwide Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Universal Donor Natural Killer Cells in people with Acute Myeloid Leukemia, run by Nationwide Children's Hospital at 1 site 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 16 inclusion and 14 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: looking for participants now, as of the sponsor's last update on 4 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Melinda C Triplet (6147226039, Melinda.Triplet@nationwidechildrens.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and severity of adverse events (time frame: Up to 56 days after the first NK cell infusion). 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 4 Nov 2024.