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Study Summary
No. 2008-0450:.......Blood And Marrow Transplantation; Leukemia; Pediatrics......Dean A. Lee......Pediatrics
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Study Summary Title
Study Summary
Number:
2008-0450
Study Title:A Single-center Open-label Phase I Study of ALT-801 for ex vivo Maturation and in vivo Retargeting of Haploidentical Natural Killer Cells Delivered Following Fludarabine, Cytarabine, and G-CSF in Patients with Relapsed/Refractory Acute Myeloid Leukemia
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Physician New Patient Referral
Name:Dean A. LeePatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:PediatricsReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-6620
Contact us about clinical trials
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General Information
Disease Group:Blood And Marrow Transplantation
Leukemia
Pediatrics
Supported By:Altor Bioscience Corporation
Phase of Study:Phase IReturn
Visit:
At least twice weekly until neutrophil counts recover, then once weekly.
Treatment
Agents:
ALT-801
Cytarabine
Fludarabine
G-CSF
Natural Killer Cells
Home Care:G-CSF injections may be given at home.
Treatment Loc:Only at MDACC
Estimated
Length of Stay
in Houston:
One hospitalization of 2 to 6 weeks.
Description/
Intervention:
The goal of this clinical research study is to learn if an investigational
therapy including fludarabine, cytarabine, G-CSF (filgrastim), a donor's NK
cells, and ALT-801 can be given reliably and safely in patients with AML. NK
cells are a type of white blood cell that fights infection and cancer.

Your leftover NK cells from the leukapheresis procedures will be tested to help
show how the infused NK cells may grow, survive, and function in the
recipient's body.
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Study Objectives / Outcomes
Primary Objectives
· Determine the safety, feasibility and maximum tolerated dose of delivering haploidentical natural killer (NK) cells matured ex vivo with ALT-801 followed by intravenous infusions of ALT-801 as an alternative to interleukin-2 (IL-2) following induction with fludarabine, cytarabine, and G-CSF (FLAG).

Secondary Objectives
· Estimate the activation status of haploidentical NK cells following overnight activation with ALT-801.
· Estimate the in vivo persistence and function of haploidentical NK cells following overnight activation with ALT-801.
· Estimate the overall response of acute myeloid leukemia (AML) to this regimen.
· Determine the rate at which patients receiving this regimen are able to go to transplant and the time-to-transplantation.
· Analyze the immunogenic response to ALT-801.
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Study Status Information
Study Activation / Registration Date:
IRB Review and Approval Date:11/07/2011
Study Type:Phase I
Recruitment Status:Open
Projected Accrual:N/A
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) RECIPIENT Enrollment Inclusion Criteria (Must be met within 30 days prior to beginning the lymphodepleting conditioning regimen, unless otherwise specified):

2) Diagnosis of relapsed AML, including patients with CNS disease or previous hematopoietic stem cell transplantation, which has failed remission to at least one cycle of reinduction chemotherapy, or primary refractory AML (primary AML that has failed remission to at least two cycles of induction therapy).

3) For patients of Cohorts 2 to 4, availability of a haploidentical family peripheral blood leukocyte donor selected for best possible KIR reactivity.

4) Patient is between 2 and 59 years of age, inclusive.

5) Patient is HLA-A2.

6) Patient must have recovered from the treatment-related toxicities of prior cytotoxic agents received in the 4 weeks prior to beginning treatment on this protocol, with the exception of cytopenias resulting from persistent disease, and alopecia.

7) Karnofsky performance scale >/= 60 or Lansky >/= 60.

8) Adequate renal function defined as: For adults serum creatinine </=2 mg/dL. For children serum creatinine </=2 mg/dL or </=2 times upper limit of normal (ULN) for age (whichever is less). If abnormal creatinine level, 24h creatinine clearance >60 mL/min/1.73m^2.

9) Adequate liver function, defined as: Total bilirubin </=2 mg/dL and SGPT (ALT) </=2.5 x ULN for age (unless Gilbert's disease or abnormal liver function due to primary disease).

10) Pulmonary symptoms controlled by medication and pulse oximetry >/= 92% room air.

11) New York Heart Association classification < III

12) Negative serum test to rule out pregnancy within 2 weeks prior to registration in females of childbearing potential (non childbearing potential defined as premenarchal, greater than one year post-menopausal, or surgically sterilized).

13) Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the Investigator.

14) Negative serology for human immunodeficiency virus (HIV).

15) DONOR Enrollment Inclusion Criteria (Assessed within 7 days of apheresis, unless otherwise specified):

16) Related to recipient (sibling, parent, offspring, offspring of a sibling)

17) HLA-haploidentical to recipient (need not be re-tested if already performed previously, provided copies of the original results are available)

18) Able and willing to undergo apheresis

19) Willing to donate blood for baseline chimerism assessment

20) Negative serum test to rule out pregnancy within two weeks prior to registration in females of childbearing potential (non childbearing potential defined as premenarchal, greater than one year post-menopausal, or surgically sterilized)

21) Donor must meet institutional eligibility criteria for allogeneic blood stem cell donation including infectious disease screening panel (Hepatitis B, Hepatitis C, HIV, HTLV, CMV, RPR, Chagas, and West Nile Virus) and CBC, differential and platelet studies.

22) Donor must meet stem cell donor eligibility criteria as set forth in 21 CFR 1271 subpart C.

23) The preferred Donor will be selected as the most alloreactive of the available haploidentical related donors on the basis of predicted NK cell alloreactivity using Recipient and Donor HLA type. If necessary, the best of equally alloreactive donors will be determined by Donor KIR type. NK alloreactivity is defined as a KIR gene is present on the Donor NK cells for which the HLA haplotype (KIR ligand) for the KIR receptor in question is absent in the Recipient, and the HLA haplotype (KIR ligand) for the KIR receptor in question is present in the Donor.

Exclusion Criteria:1) RECIPIENT Enrollment: Failed attaining remission with any previous FLAG therapy.

2) Recipient Enrollment: Investigational therapies in the 4 weeks prior to beginning treatment on this protocol.

3) Recipient Enrollment: Congestive heart failure <6 months prior to screening.

4) Recipient Enrollment: Unstable angina pectoris <6 months prior to screening.

5) Recipient Enrollment: Myocardial infarction <6 months prior to screening.

6) DONOR Enrollment (Assessed within 7 days of apheresis, unless otherwise specified): Active infection [defined as receiving antimicrobial treatment (excluding prophylactic antibiotics)] and/or febrile.

7) Donor Enrollment (Assessed within 7 days of apheresis, unless otherwise specified): Pregnant females.

8) Donor Enrollment (Assessed within 7 days of apheresis, unless otherwise specified): Breast-feeding females.

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Links
Registration Number: NCT01478074
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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