Acute Myelogenous Leukemia Clinical Trial
Official title:
Reduced Intensity Haploidentical Hematopoietic Stem Cell Transplantation (HSCT) Supplemented With Donor Natural Killer (NK) Cell Infusions in Patients With High Risk Myeloid Malignancies Who Are Unsuitable for Fully Myeloablative Transplantation
Verified date | December 2017 |
Source | Masonic Cancer Center, University of Minnesota |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
RATIONALE: Giving chemotherapy, such as fludarabine phosphate and cyclophosphamide, and total
body irradiation, before peripheral blood stem cell transplant helps stop the growth of
cancer cells. It may also stop the patient's immune system from rejecting the donor's stem
cells. When the healthy stem cells and natural killer (NK) cells from a donor are infused
into the patient they may help the patient's bone marrow make stem cells, red blood cells,
white blood cells, and platelets. Giving IL-2 (aldesleukin) after NK cell infusion may
stimulate them to kill any remaining cancer cells.
PURPOSE: This phase I/II (currently enrolling in phase II) trial is studying how well a donor
natural killer cell infusion works in treating patients who are undergoing donor stem cell
transplant for acute myeloid leukemia.
Status | Completed |
Enrollment | 50 |
Est. completion date | March 2011 |
Est. primary completion date | March 2011 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 70 Years |
Eligibility |
Inclusion Criteria: - 4.2 High risk acute myeloid leukemia (AML) fitting within one of the following disease groups: - Primary induction failure defined as no complete remission (CR) after two or more induction cycles. For primary induction failure (PIF) or refractory AML, the patient must have <5% circulating blasts (and <1000 absolute circulating blasts) beyond Day 28 after last chemo. During work-up period if circulating blasts rise above these levels, the patient is ineligible. The use of hydrea or other non-induction cytotoxic agents is not allowed to reduce blasts and achieve this eligibility. If the blasts are higher than these limits, the patient should be treated on an alternative therapeutic protocol or receive another reinduction attempt. (See section 7 regarding final check of blast status within 7 days of preparative regimen start). - Relapsed AML with low disease burden must have less than 5% marrow blasts at time of enrollment for patients who did not receive re-induction or measured at least 28 days from the start of reinduction therapy for patients who did receive re-induction (maximum of 2 re-induction attempts). Patients who have relapsed more than 12 months following a prior HCT and did not reach CR following one re-induction cycle but have less than 10% marrow blasts are eligible. - CR3 or greater. This will include CRp defined as CR without platelet recovery to 100,000/mcL. - CR1 or CR2 with high risk features (therapy induced, prior myelodysplastic syndrome [MDS] or myeloproliferative disease [MPD], high risk cytogenetic or molecular phenotype) with no available alternate (sibling, unrelated donor [URD] or umbilical cord blood [UCB]) donors. Patients with prior central nervous system (CNS) involvement are eligible provided that it has been treated and CFS must be clear for at least 2 weeks prior to enrollment. - Available related HLA-haploidentical donor (3-5 of 6 HLA, A, B and DRB1 matched) - Karnofsky performance status > 50 - Pulmonary Function: oxygen saturation = on room air and diffusion lung capacity for carbon monoxide (DLCOcor) = 40% - Cardiac Function: Ejection fraction (EF) = 30%, 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 Day 0 - Women of child bearing potential must have a negative pregnancy test within 14 days prior to study registration and agree to use adequate birth control during study treatment - Human anti-mouse antibody (HAMA) monitoring: All subjects will be questioned about prior exposure to antibody therapy (including OKT3, rituximab, trastuzumab, etc). - For subjects with no prior antibody therapy exposure, no further action will be taken - For subjects who have received previous antibody therapies 10 ml of serum will be drawn before starting therapy. The presence of HAMA will not preclude proceeding with treatment. - Voluntary written consent signed before performance of any study related procedure not part of the normal medical care. Exclusion Criteria: - Biphenotypic leukemia - New or progressive pulmonary infiltrates on screening chest x-ray or chest computed tomography (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 (2 weeks for presumed or documented fungal infections). Surgical resection waives any waiting requirements. - Uncontrolled bacterial or viral infections. Chronic asymptomatic viral hepatitis is allowed. - Known hypersensitivity to any of the study agents used - Received other investigational drugs within the 14 days before enrollment Donor Selection: - 12-75 years of age - > 40 kilogram body weight - In general good health as determined by the evaluating physician - Donors must be HLA-A, B, DRB1 haploidentical (3-5/6 antigens HLA, A, B, DRB1) match to recipient. Patients and donors will be typed for HLA-A, B and C using at least intermediate resolution DNA techniques for DRB1 at high (allele) resolution. KIR B genotyping will be done on all haploidentical donors, and when feasible, the donor with the most favorable KIR gene profile will be used. - Able and willing to have up to 4 separate apheresis collections per formed - Not pregnant - Human immunodeficiency virus (HIV): HIV-1, HIV-2 negative; HTLV-1, HTLV-2 negative, Hepatitis B and C negative - 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 | Disease-free Survival at 6 Months | Number of patients alive without evidence of disease at 6 months after transplant | Month 6 | |
Primary | Disease-free Survival at 1 Year | Number of patients alive without evidence of disease at 1 year after transplant | 1 Year | |
Secondary | In Vivo Expansion of a Donor NK Cells NK Cell Product | Number of patients with in vivo expansion of donor NK cells. In vivo expansion of NK cell is defined as detection of >100 donor-derived NK cells per microliter of blood. | 12 - 14 days after NK cell infusion | |
Secondary | Number of Patients With Graft Failure | Number of patients with graft failure defined as <500 donor neutrophils count by day 28 in the absence of residual or relapsed leukemia | Day 28 | |
Secondary | Incidence of Grade III-IV Acute Graft Versus Host Disease | Grade III-IV acute graft versus host disease is a severe short term complication created by infusion of donor cells into a foreign host | Month 6 | |
Secondary | Number of Patients With Treatment-Related Mortality | Death within the first 100 days related to treatment in patients without relapse or persistent disease. | Day 100 | |
Secondary | Incidence of Chronic Graft Versus Host Disease | Chronic graft versus host disease is a severe long term complication created by infusion of donor cells into a foreign host | 1 Year | |
Secondary | Number of Patients With Disease Relapse | Disease relapse is the recurrence of leukemia in patients who had cleared their leukemia after treatment. Patients with persistent leukemia are not evaluable for relapse. | 1 Year | |
Secondary | Incidence of Post-transplant Lymphoproliferative Disorder (PTLD) | Post-transplant lymphoproliferative disorder (PTLD) is a virally-driven cancer of the lymphoid cells caused by immunosuppressive drugs taken after allogeneic stem cell transplantation to prevent or control graft versus host disease. | 1 Year |
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