NCT01478074

ALT-801-activated Natural Killer Cells After FLAG Induction for Acute Myeloid Leukemia

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

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Altor BioScience · Industry
• Sex: All
• Age: 2 Years – 59 Years
• Healthy volunteers: Not accepted

Summary

This is a single-center open-label phase I clinical trial of delivering haploidentical natural killer (NK) cells matured ex vivo with ALT-801 followed by intravenous infusions of ALT-801 in patients with relapsed/refractory Acute Myeloid Leukemia (AML). The study will be conducted at M.D. Anderson Cancer Center (MDACC) and MDACC Children's Cancer Hospital in Houston, Texas.

Detailed description

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.

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	G-CSF	5 mcg/kg daily from day -7 until post-nadir ANC \> 1000
DRUG	Cytarabine	2 g/m2 daily from day -6 through -2
DRUG	Fludarabine	30 mg/m2 daily from day -6 through -2
BIOLOGICAL	Donor Natural Killer (NK) cells	Infused once on day 0. Four cohorts of escalating doses receiving 0, 1, 10, or 20 x 10\^6 cells/Kg
BIOLOGICAL	ALT-801	0.04 mg/kg IV thrice weekly for 8 doses beginning day +2

Timeline

• Start date: 2011-11-01
• Primary completion: 2013-10-01
• Completion: 2013-11-01
• First posted: 2011-11-23
• Last updated: 2014-01-03

Locations

1 site across 1 country: United States