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
Hematopoietic stem cell transplantation (SCT) is an effective treatment for acute myeloid
leukemia (AML) and myelodysplastic syndrome (MDS). For patients transplanted in first
remission or with low risk MDS, approximately 60% of patients have achieved long-term
disease free survival. Patients with relapsed leukemia have a poorer outcome; the long-term
disease free survival rate for relapsed AML is 5-10% without hematopoietic stem cell
transplantation (HSCT). With HSCT, survival after relapse approaches 40%, but success
depends greatly on whether patients are in remission at the time of transplant. Many
relapsed patients have refractory chemoresistant disease and never attain remission to be
eligible for potentially curative HSCT, or develop significant complicating comorbidities
during the prolonged intensive reinduction of their disease. Thus, improved strategies for
achieving remission in relapsed patients prior to transplantation are critical to improving
the survival of these patients. Relapsed/refractory AML requires remission prior to
allogeneic HSCT for optimal survival, but responds poorly to chemotherapy. Human leukocyte
antigen (HLA)-haploidentical, NK-enriched peripheral blood cell infusions may augment
induction chemotherapy in patients with poor prognosis AML, but there are significant
toxicities related to the IL-2 infusions given for optimal NK cell activity. The purpose of
this trial is to estimate the toxicity and feasibility of treating relapsed/refractory AML
with FLAG chemotherapy followed by haploidentical donor-derived natural killer (NK) cells
using ALT-801 for ex vivo and in vivo NK cell activation as an alternative to interleukin-2
(IL-2).
ALT-801 is a genetically engineered fusion protein, that is, a single protein made by
combining the DNA of two or more different genes. ALT-801 is a combination of IL-2 (an
important protein for stimulating immune cells) and a binding portion that recognizes tumor
cells.
The primary objective of this study is to evaluate the safety and feasibility of an infused
allogeneic donor NK cell product and ALT-801 following a FLAG preparative regimen to treat
relapsed/refractory acute myelogenous leukemia. The primary endpoint for toxicity is the
absence of NK cell Product or ALT-801-related grade 2 toxicity, excluding grade 2 fever,
rigor/chills, fatigue, vomiting/nausea, pruritus/itching, electrolyte imbalance,
hypoalbuminemia or lymphopenia within 21 days of the ALT-801 or NK cell product infusion.
The primary endpoint of feasibility is defined as being able to infuse NK-cells at the
maximum tolerated cell dose or the highest dose level on day 0 and complete all 8 planned
doses of ALT-801, with a safety that does not exceed toxicity limits, in greater than or
equal to 7 of 10 subjects.
Recipient
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of NK cells
Determined by the maximum tolerated dose of NK cells that can be given in combination with ALT-801 with less than 1/3 of patients experience dose-limiting toxicities related to the NK cells or ALT-801.
18 months
Yes
Hing C Wong, PhD
Study Director
Altor Bioscience Corporation
United States: Food and Drug Administration
CA-ALT-801-02-08
NCT01478074
November 2011
Name | Location |
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MD Anderson Cancer Center | Houston, Texas 77030-4096 |