Ignite Creation Date:
2025-12-25 @ 2:39 AM
Ignite Modification Date:
2025-12-30 @ 7:55 PM
Study NCT ID:
NCT05503134
Status:
RECRUITING
Last Update Posted:
2024-11-04
First Post:
2022-02-14
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Safety and Efficacy of Expanded, Universal Donor Natural Killer Cells for Relapsed/Refractory AML
Sponsor:
Nationwide Children's Hospital
Organization:
Study Overview
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
Status:
RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
KARMA
Brief 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. 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:
I. To estimate the efficacy of UD- NK cells with FLA chemotherapy in pediatric and young adult patients with relapsed/refractory AML.
EXPLORATORY OBJECTIVES:
I. 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.
PRIMARY OBJECTIVE:
I. 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:
I. To estimate the efficacy of UD- NK cells with FLA chemotherapy in pediatric and young adult patients with relapsed/refractory AML.
EXPLORATORY OBJECTIVES:
I. 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:
1. \<CR after cycle 1
2. Additional cycle is needed to bridge the patient to HSCT
Criteria to begin Cycle 2:
1. ≥28 days since the first NK Cell infusion
2. ≥2 days since the last NK Cell infusion in cycle 1
3. Bone marrow evaluation after cycle 1 complete
4. It is suggested but not required for ANC \> 500/uL AND platelets \>50,000/uL prior to beginning cycle 2
5. Prior treatment related toxicities must have resolved to ≤ Grade 2
NK Cell Dose Levels:
1. Dose level 1: 1.00x10\^7 NK cell/kg (±20%) each dose for 6 doses per cycle
2. Dose level 2: 3.00x10\^7 NK cell/kg (±20%) each dose for 6 doses per cycle
3. 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.
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:
1. \<CR after cycle 1
2. Additional cycle is needed to bridge the patient to HSCT
Criteria to begin Cycle 2:
1. ≥28 days since the first NK Cell infusion
2. ≥2 days since the last NK Cell infusion in cycle 1
3. Bone marrow evaluation after cycle 1 complete
4. It is suggested but not required for ANC \> 500/uL AND platelets \>50,000/uL prior to beginning cycle 2
5. Prior treatment related toxicities must have resolved to ≤ Grade 2
NK Cell Dose Levels:
1. Dose level 1: 1.00x10\^7 NK cell/kg (±20%) each dose for 6 doses per cycle
2. Dose level 2: 3.00x10\^7 NK cell/kg (±20%) each dose for 6 doses per cycle
3. 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 Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: