IIT PH1 KDS-1001 in Patients With CML

Study Overview
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Brief Summary
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This open label, non-randomized, prospective phase I study is designed to evaluate if the addition of natural killer cell therapy (KDS-1001) to tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML) patients with persistent or recurrent molecular residual disease (MRD) after at least one year of TKI therapy will allow patients to achieve RT-PCR negativity (MRD negative). This may have implications for future TKI cessation studies.

Official Title
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A Phase I Trial of Incorporating Natural Killer (K-NK) Cells for Patients With Chronic Myeloid Leukemia (CML) and Molecular Residual Disease After Tyrosine Kinase Inhibitor (TKI) Therapy

Conditions
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CML (Chronic Myelogenous Leukemia

Intervention / Treatment
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* Drug: KDS-1001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with non-blast phase CML by standard definition. This should be confirmed by presence of the Philadelphia chromosome or variants of the (9;22) translocation by cytogenetics, FISH or with a positive RT-PCR for BCR-ABL. Repeat marrow not required for enrollment although documentation of current chronic phase disease is required. Chronic Phase CML is defined as follows: <15% blasts in peripheral blood and marrow <30% blasts plus promyelocytes in peripheral blood and marrow <20% basophils in peripheral blood >100 x 109/L platelets No evidence of extramedullary leukemic involvement with the exception of hepatosplenomegaly. Accelerated Phase CML is defined as follows: <30% blasts in blood, marrow or both No evidence of extramedullary leukemic involvement with the exception of hepatosplenomegaly. > 18 years of age and able to provide informed consent Patients must have been on TKI therapy for CML for at least 1 year prior to enrollment at minimum goal doses. Imatinib 300mg PO daily Dasatinib 70mg PO daily Nilotinib 200mg PO BID Bosutinib 300mg PO daily Ponatinib 30mg PO daily Lower than goal doses are allowed IF documented by the treating physician that the goal dose was not tolerable due to toxicity. Patient must have been on their most recent TKI consistently for at least 6 months prior to enrollment on study Must be expected to remain on current TKI for at least 6 months following last infusion, unless there is progression of disease. Detectable BCR-ABL transcripts measured by RT-PCR at a CLIA-approved laboratory and reported on the IS with a value of >0.01% within 28 days prior to study enrollment. The chosen RT-PCR test must be sensitive enough to detect a 4.5 log reduction in BCR/ABL transcripts measured in peripheral blood. Performance status must be ECOG PS 0, 1, or 2. Woman of childbearing potential and is willing to use 2 highly effective methods of contraception while receiving study treatment and for an additional 3 months after the last dose of protocol-specified therapy. Male who has a female partner of childbearing potential, and is willing to use 2 highly effective forms of contraception for at least an additional 3 months after the last dose of protocol-specified therapy. Exclusion Criteria: Patients who meet any of the following criteria will be excluded from the study: Current blast crisis phase disease by standard definition from the NCCN Pregnant or lactating females On other investigational agents for CML within 4 weeks of study enrollment Platelets of <50,000/mm3, ANC <500/mm3 or hemoglobin < 7.5 g.dL Abnormal screening laboratory values as defined below: AST (SGOT) and/or ALT (SGPT) and/or alkaline phosphatase ≥ 5 x upper limit of normal (ULN) Total bilirubin >1.5 x ULN (unless related to Gilbert´s or Meulengracht disease or leukemic infiltration) Creatinine ≥ 3 ULN or creatinine clearance < 50 mL/min (calculated) Those with residual toxicity of >grade 1 from prior therapy in areas that may be expected to worsen over time; those with residual toxicities of grade 2 which are stable prior to enrollment and the natural history of which would be expected to be 'no change' over time are allowed; those with grade 3 or 4 residual toxicities are not. Positive test for human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS) Positive hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating acute or chronic infection (those with prior infection that is now post treatment and PCR negative are allowed) Current use of immunosuppressive medications at the time of study enrollment and within 2 weeks of any study treatments, except: Intranasal, inhaled, topical steroids, or local steroid injection Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or equivalent Steroids as premedication for hypersensitivity reactions at physiologic doses ≤10 mg/day of prednisone or equivalent Patients with other major medical or psychiatric illnesses, which the treating physician feels, could seriously compromise tolerance or compliance to this protocol. Diagnosis of prior immunodeficiency or organ transplant requiring immunosuppressive therapy Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, deep vein thrombosis, or symptomatic pulmonary embolism Known prior or suspected hypersensitivity to study drugs or any component in their formulations Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible Diagnosis of any other malignancy within 3 years, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the breast or of the cervix, low grade prostate cancer on surveillance without any plans for treatment intervention, or prostate cancer that has been adequately treated with prostatectomy or radiotherapy and currently with no evidence of disease or symptoms Active infection requiring systemic therapy
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KDS-1001<br>KDS-1001 is infused on Day 1 of each 14 day cycle. Patients will receive 6 cycles of KDS-1001 treatment. | Drug: KDS-1001<br>* Cycles 1-6 (14 days per cycle) 1 x 109/KDS-1001 cells/infusion administered on day 1 of each cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Molecular Response | At least one (1) log reduction in IS OR negative to at least MR4.5 via PCR-based testing | End of Treatment up to two weeks | 
| Safety of KDS-1001 | Number of adverse events as measured by self report | End of Study up to two years |