NK cells (KDS-1001) in Treating Patients with Recurrent or Refractory Acute Myeloid Leukemia
This phase I trial studies the best dose and safety of KDS-1001 to see how well it works in treating patients with acute myeloid leukemia that has come back (recurrent) or has not responded to treatment (refractory). KDS-1001 is derived from natural killer (NK) cells. NKs 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.
Inclusion Criteria
- INDUCTION PHASE: Patients with one of the following diagnoses: * Relapsed or primary refractory acute myeloid leukemia (AML), including ** Patients with relapsed AML after allogeneic stem cells transplantation, including those who have received donor lymphocyte infusions ** Isolated central nervous system (CNS) or extramedullary disease *** Note: a response monitoring plan must be developed a priori for subjects with extramedullary disease ** Received1-3 prior lines of therapy which includes chemotherapy, hypomethylating agents, venetoclax or targeted therapy
- INDUCTION PHASE: Patient age >= 18 years
- INDUCTION PHASE: Patient weight >= 42 kilograms (kg)
- INDUCTION PHASE: Karnofsky or Lansky performance scale (PS) greater or equal to 70, or, Eastern Cooperative Oncology Group (ECOG) score 0-2
- INDUCTION PHASE: Serum creatinine =< 2 mg/dl and/or creatinine clearance greater or equal than 40 cc/min
- INDUCTION PHASE: Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO) >= 50% of expected, corrected for hemoglobin
- INDUCTION PHASE: Total bilirubin =< 2 mg/dl or =< 2.5 x upper limit of normal (ULN) for age (unless Gilbert's syndrome)
- INDUCTION PHASE: Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x ULN for age
- INDUCTION PHASE: Left ventricular ejection fraction >= 40%
- INDUCTION PHASE: Patients with seizure disorder may be eligible if seizures well controlled
- INDUCTION PHASE: 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)
- INDUCTION PHASE: Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the investigator
- INDUCTION PHASE: Ability to understand and willingness to sign the written informed consent document
- INDUCTION PHASE: Negative serology for human immunodeficiency virus (HIV)
- INDUCTION PHASE: Patients on hydrocortisone for adrenal insufficiency or on inhaled or topical steroids are eligible
- MAINTENANCE PHASE: Patients must meet all criteria; * CR, CRi, or PR * Ineligible, unable or unwilling to undergo HSCT * Patient is >= 35 days from first KDS-1001 infusion in induction phase
- MAINTENANCE PHASE: Patient age >= 18 years
- MAINTENANCE PHASE: Patient weight >= 42 kg
- MAINTENANCE PHASE: Performance status: Karnofsky or Lansky Performance Scale (PS) greater or equal to 70, or ECOG score 0-2
- MAINTENANCE PHASE: Renal function: Serum creatinine =< 2 mg/dl and/or creatinine clearance greater or equal to 40 cc/min
- MAINTENANCE PHASE: 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
- MAINTENANCE PHASE: CNS: Patients with seizure disorder are eligible if seizures well controlled
- MAINTENANCE PHASE: 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)
- MAINTENANCE PHASE: Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the Investigator
- MAINTENANCE PHASE: Ability to understand and willingness to sign the written informed consent document
- MAINTENANCE PHASE: Negative serology for human immunodeficiency virus (HIV) – negative serology pre-induction would suffice
- MAINTENANCE PHASE: Patients on hydrocortisone for adrenal insufficiency or on inhaled or topical steroids are eligible
- MAINTENANCE PHASE: Both males and females and members of all races and ethnic groups are eligible for this trial
Exclusion Criteria
- INDUCTION PHASE: Investigational therapies in the 3 weeks prior to beginning treatment on this protocol
- INDUCTION PHASE: Patients receiving any concurrent therapy including but not limited to chemotherapy, targeted therapy, radiation therapy, or immunotherapy for relapsed/refractory (R/R) AML
- INDUCTION PHASE: Any comorbidities that in the opinion of the investigator will preclude receiving fludarabine or cytarabine
- INDUCTION PHASE: 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 cytomegalovirus (CMV), human papillomavirus (HPV), BK virus, hepatitis C virus (HCV), hepatitis B virus (HBV), etc. is NOT considered as an exclusion criteria
- INDUCTION PHASE: Uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease
- INDUCTION PHASE: Active graft versus host disease (GVHD)
- INDUCTION PHASE: Prednisone dose is > 20 mg/day or >0.25mg/kg, whichever is higher will be excluded
- INDUCTION PHASE: Patients with donor-specific antibodies with mean fluorescence intensity (MFI) > 5000 will be ineligible
- MAINTENANCE PHASE: Patients receiving any concurrent therapy including but not limited to chemotherapy, targeted therapy, radiation therapy, or immunotherapy for R/R AML
- MAINTENANCE PHASE: 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
- MAINTENANCE PHASE: Uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease
- MAINTENANCE PHASE: Active GVHD
- MAINTENANCE PHASE: Patient on corticosteroids to control GVHD
- MAINTENANCE PHASE: Patients on systemic steroids for asthma and prednisone dose is > 20 mg/day or > 0.25 mg/kg, whichever is higher will be excluded
Additional locations may be listed on ClinicalTrials.gov for NCT04220684.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVES:
I. To determine the recommended phase II dose of KDS-1001. (Induction phase)
II. To determine the overall response rate (complete response [CR], CR with incomplete hematologic recovery [CRi] & morphologic leukemia-free state [MLFS]). (Induction phase)
III. To determine the safety of maintenance dosing. (Maintenance phase)
IV. To determine the feasibility of maintenance dosing. (Maintenance phase)
V. To estimate the the median duration of remission. (Maintenance phase)
SECONDARY OBJECTIVES:
I. To determine percentage of patients with measurable residual-negative remission. (Induction Phase)
II. To determine percentage of patients proceeding to an allogenic transplant. (Induction Phase)
III. Estimate the median time to neutrophil and platelet count recovery (Induction phase)
IV. Estimate the incidence of cytomegalovirus (CMV) reactivation. (Induction phase)
V. Estimate the incidence of CMV seroconversion. (Induction phase)
VI. Estimate the median duration of remission. (Induction phase)
VII. Estimate the incidence of infectious complications. (Induction phase)
VIII. To determine the progression free survival. (Induction phase)
IX. To determine the percentage of patients with overall survival. (Induction phase)
X. Duration of CR, CRi, or PR. (Maintenance phase)
XI. To determine the percentage of patients with measurable residual-negative remission. (Maintenance phase)
XII. To estimate the incidence of infections complications. (Maintenance phase)
XIII. To determine the percentage of patients with progression free survival. (Maintenance phase)
EXPLORATORY OBJECTIVES:
I. Determine the persistence of KDS-1001. (Induction phase)
II. Characterize in vivo expansion of KDS-1001. (Induction phase)
III. Determine the immunophenotype and function of KDS-1001. (Induction phase)
IV. Chimerism analysis in patients who have had post-transplant relapses. (Induction phase)
V. Correlation between DSA and KDS-1001 persistence/immunogenicity. (Induction phase)
VI. Correlation between DSA and KDS-1001 persistence/immunogenicity. (Maintenance phase)
VII. Determine the persistence of KDS-1001. (Maintenance phase)
VIII. Development of DSA. (Maintenance phase)
IX. Incidence of CMV reactivation. (Maintenance phase)
OUTLINE:
INDUCTION PHASE: Patients who are able to tolerate intensive chemotherapy, and not insensitive to cytarabine receive fludarabine intravenously (IV) and cytarabine IV on days -6 to -2 as a conditioning regimen, followed by 6 doses of KDS-1001 cells given thrice weekly for two weeks.
MAINTENANCE PHASE: Patients who complete induction phase and who attain a CR/CRi/PR within the follow-up period and who are ineligible, unable or unwilling to undergo HSCT, may then enter the maintenance phase. KDS-1001 will be initiated no earlier than 35 days after first dose of KDS-1001 in the induction phase and will continue being dosed each 28 days for up to an additional 12 months.
Additionally, patients undergo bone marrow aspiration and biopsy, blood sample collection and optional echocardiography on study.
After completion of study treatment, patients are followed up to day 56 for the induction phase, and up to 12 months following initiation of maintenance therapy. Follow up will terminate if patient relapses.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationOhio State University Comprehensive Cancer Center
Principal InvestigatorSumithira Vasu
- Primary IDOSU-18336
- Secondary IDsNCI-2019-05150, 2019C0170
- ClinicalTrials.gov IDNCT04220684