Ph1 Trial Test Safety of IL-21 NK Cells for Induction of R/R AML
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|ClinicalTrials.gov Identifier: NCT04220684|
Recruitment Status : Recruiting
First Posted : January 7, 2020
Last Update Posted : February 18, 2022
|Condition or disease||Intervention/treatment||Phase|
|Allogeneic Stem Cell Transplant Recipient Blasts 10 Percent or More of Bone Marrow Nucleated Cells Recurrent Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia||Drug: Cytarabine Hydrochloride Drug: Fludarabine Biological: Membrane-bound Interleukin-21-Expanded Haploidentical Natural Killer Cells||Phase 1|
I. 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).
I. 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.
I. 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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||June 1, 2020|
|Estimated Primary Completion Date :||December 31, 2022|
|Estimated Study Completion Date :||December 31, 2022|
Experimental: Conditioning Regimen
Fludarabine 30 mg/m2/day (day -6 to day -2) and Cytarabine 2g/ m2/day (days -6 to day -2)
Drug: Cytarabine Hydrochloride
Other Name: Fluradosa
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
Biological: Membrane-bound Interleukin-21-Expanded Haploidentical Natural Killer Cells
Given via infusion
- 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.
- Complete response (CR) [ Time Frame: Up to day 56 ]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.
- CR with incomplete hematologic recovery [ Time Frame: Up to day 56 ]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.
- Morphologic leukemia-free state [ Time Frame: Up to day 56 ]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.
- Median relapse free survival [ Time Frame: Up to day 56 ]Will use descriptive statistics to summarize the demographic and clinical characteristics of the patients on this study.
- Median time to neutrophil and platelet count recovery [ Time Frame: Up to day 56 ]Will use descriptive statistics to summarize the demographic and clinical characteristics of the patients on this study.
- Median duration of remission [ Time Frame: Up to day 56 ]Will use descriptive statistics to summarize the demographic and clinical characteristics of the patients on this study.
- 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 ]
- Identification of In-vivo expansion of NK cells [ Time Frame: Up to day 56 ]Peripheral blood will be obtained before therapy, during the NK cell treatment period, and after NK cell treatment. The studies may include flow cytometry analyses and sorting and molecular studies. Donor NK-cell expansion will be defined as an absolute circulating donor-derived NK cell count that increases above the post-infusion level.
- Chimerism analysis to determine origin and number of circulating NK cells [ Time Frame: Up to day 56 ]Chimerism may be determined by flow cytometry using haplotype-specific antibodies. Chimerism may be determined by short tandem repeat polymorphisms. When there is a sex-mismatch between the donor and the recipient, assays based on determining the frequency of sex-chromosomes may be used. Testing may be altered by principal investigator or designee.
- Number of donor human leukocyte antigen (HLA) detection [ Time Frame: Up to day 56 ]Donors with distinct HLA A or B antigens that can be detected by flow cytometry will be chosen. This will enable tracking of infused cells.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04220684
|Contact: The Ohio State University Comprehensive Cancer Center||1-800-293-5066||OSUCCCClinicaltrials@osumc.edu|
|Contact: Nicole Szuminski||614-688-9796||Nicole.Szuminski@osumc.edu|
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center||Recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Sumithira Vasu, MBBS 614-293-8197 Sumithira.Vasu@osumc.edu|
|Principal Investigator: Sumithira Vasu, MBBS|
|Principal Investigator:||Sumithira Vasu, MBBS||Ohio State University Comprehensive Cancer Center|