Myelodysplastic Syndrome Clinical Trial
Official title:
Haploidentical Donor Natural Killer (NK) Cell Infusion With Intravenous Recombinant Human IL-15 (rhIL-15) in Adults With Refractory or Relapsed Acute Myelogenous Leukemia (AML)
Verified date | November 2017 |
Source | Masonic Cancer Center, University of Minnesota |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This is a single center, "modified standard design" dose escalation study designed to determine the maximum tolerated, minimum efficacious dose (MTD/MED) of IL-15 (Intravenous Recombinant Human IL-15) and incidence of donor natural killer (NK) cell expansion by day +14 when given after haploidentical donor NK cells in patients with relapse or refractory acute myelogenous leukemia (AML).
Status | Completed |
Enrollment | 26 |
Est. completion date | March 2015 |
Est. primary completion date | March 2015 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - = 18 years of age - Meets one of the following disease criteria: - Primary acute myelogenous leukemia (AML) induction failure: no complete response (CR )after 2 or more induction attempts - Relapsed AML or Secondary AML (from MDS or treatment-related): not in CR after 1 or more cycles of standard induction therapy. For patients > 60 years of age the 1 cycle of standard chemotherapy is not required if either of the following is met: - relapse within 6 months of last chemotherapy - blast count <30% within 10 days of starting protocol - AML relapsed > 2 months after transplant who do not have the option of donor lymphocyte infusions (e.g. recipients of autologous or umbilical cord blood [UCB] transplants) Patients with prior central nervous system (CNS) involvement are eligible provided that it has been treated and cerebrospinal fluid (CSF) is clear for at least 2 weeks prior to enrollment. CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment. - Available related HLA-haploidentical donor (3-5 of 6 HLA-A, B and C) - Karnofsky Performance Status > 50% - Adequate organ function defined as: - Creatinine: = 2.0 mg/dL - Hepatic: Liver function tests (LFT's) < 5 times upper limit of institutional normal (ULN) - Pulmonary Function: oxygen saturation = 90% on room air and pulmonary function >50% corrected DLCO and FEV1 Testing required only if symptomatic or prior known impairment. - Cardiac Function: Ejection fraction (EF) = 40%, no uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities - Able to be off prednisone or other immunosuppressive medications for at least 3 days prior to Natural Killer (NK) cell infusion (excluding preparative regimen pre-medications) - Women of child bearing potential and men with partners of child bearing potential must agree to use effective contraception during therapy and for 4 months after completion of therapy. - Voluntary written consent Exclusion Criteria: - Bi-phenotypic acute leukemia - Transplant < 60 days prior to study enrollment - Pregnant or breastfeeding - The agents used in this study include those that fall under Pregnancy Category D - have known teratogenic potential. Women of child bearing potential must have a negative pregnancy test within 14 days of study treatment start - Active autoimmune disease - History of severe asthma, presently on chronic medications (a history of mild asthma not requiring therapy is eligible) - New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that has not been evaluated with bronchoscopy, if feasible. Infiltrates attributed to infection must be stable/improving (with associated clinical improvement) after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections). Surgical resection waives any waiting requirements. - Uncontrolled bacterial or viral infections - chronic asymptomatic viral hepatitis is allowed - Pleural effusion large enough to be detectable on chest x-ray - Known hypersensitivity to any of the study agents used - Received investigational drugs within the 14 days before enrollment - Known active CNS involvement Criteria For Initial Donor Selection: - Related donors (sibling, parent, offspring, parent or offspring of an HLA identical sibling) - 14-75 years of age - At least 40 kilogram body weight - In general good health as determined by the evaluating medical provider - HLA-haploidentical donor/recipient match (low resolution) - Not pregnant - Agree to undergo donor viral screening panel - Able and willing to undergo apheresis - Voluntary written consent |
Country | Name | City | State |
---|---|---|---|
United States | Masonic Cancer Center, University of Minnesota | Minneapolis | Minnesota |
Lead Sponsor | Collaborator |
---|---|
Masonic Cancer Center, University of Minnesota |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Maximum Tolerated/Minimum Efficacious Dose | Determine the maximum tolerated, minimum efficacious dose (MTD/MED) of recombinant human IL-15; dose limiting toxicity (DLT) occurring during the first 42 days after the NK cell infusion; MED = if 2 of 3 patients or 4 of 6 patients has an in vivo NK cell count >2500, then dose escalation with cease as it will be in the range of a biologic dose which may achieve the goal of in vivo expansion without pushing IL-15 doses higher to toxicity. | Day 42 | |
Secondary | Incidence of Expansion of Natural Killer Cells | defined by measuring an absolute circulating donor-derived NK cell count of >100 cells/µl in the patient's peripheral blood by day +14 after the NK cell infusion. | Day 14 after Infusion | |
Secondary | Treatment Related Mortality (TRM) | In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation. | Day 1 of Treatment until Day of Death | |
Secondary | Rate of CRp | defined as leukemia clearance (< 5% marrow blasts and no peripheral blood blasts) and neutrophil recovery without platelet recovery. | Day 28-42 |
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