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

NCT01478074 | Withdrawn Phase 1

• 1 other identifier: CA-ALT-801-02-08
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia; Relapsed leukemia; Refractory leukemia; Natural Killer Cells; Adoptive immunotherapy; NK cell infusion; Haploidentical; KIR mismatch; Fludarabine; Cytarabine; Ara-C; ALT-801

Outcome Measures

Primary Outcomes (2)

• 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

• Safety of delivering NK cells and ALT-801 in combination with FLAG

  Determined by whether the maximum tolerated dose of NK cells can be given in combination with ALT-801 and FLAG chemotherapy without exceeding a rate of 0.28 for \>= Grade 3 toxicities (10% above that of FLAG therapy alone) during the treatment period.

  6 months after study completes accrual

Secondary Outcomes (5)

• Activation status of NK cells following activation with ALT-801

  6 months after study completes accrual

• In vivo persistence and function of haploidentical NK cells activated with ALT-801.

  6 months after study completes accrual

• Overall response to this regimen

  6 months after study completes accrual

• Rate of stem cell transplantation and the time-to-transplantation

  6 months after study completes accrual

• ALT-801 immunogenicity

  6 months after study completes accrual

Study Arms (1)

FLAG + NK Cells + ALT-801

EXPERIMENTAL

Drug: G-CSF; Drug: Cytarabine; Drug: Fludarabine; Biological: Donor Natural Killer (NK) cells; Biological: ALT-801

Interventions

G-CSF DRUG

5 mcg/kg daily from day -7 until post-nadir ANC \> 1000

FLAG + NK Cells + ALT-801

Cytarabine DRUG

2 g/m2 daily from day -6 through -2

FLAG + NK Cells + ALT-801

Fludarabine DRUG

30 mg/m2 daily from day -6 through -2

FLAG + NK Cells + ALT-801

Donor Natural Killer (NK) cells BIOLOGICAL

Infused once on day 0. Four cohorts of escalating doses receiving 0, 1, 10, or 20 x 10\^6 cells/Kg

FLAG + NK Cells + ALT-801

ALT-801 BIOLOGICAL

0.04 mg/kg IV thrice weekly for 8 doses beginning day +2

FLAG + NK Cells + ALT-801

Eligibility Criteria

• Age: 2 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients with relapsed AML, including those with CNS disease or previous hematopoietic stem cell transplantation, or primary refractory AML (primary AML that has failed remission to at least two cycles of induction therapy)
• For patients of Cohorts 2 to 4, availability of a haploidentical family peripheral blood stem cell donor selected for best possible KIR reactivity
• Patient is between 2 and 59 years of age, inclusive
• 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
• Zubrod performance scale (Refer to Appendix C) ≤ 2 or Lansky (Refer to Appendix D) \> 60
• 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 (which ever is less) If abnormal creatinine level, 24h creatinine clearance \> 60 mL/min/1.73m\^2
• 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)
• Pulmonary symptoms controlled by medication and pulse oximetry\> 92% room air
• New York Heart Association classification \< III
• 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)
• Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the Investigator
• Negative serology for human immunodeficiency virus (HIV)

You may not qualify if:

• Investigational therapies in the 4 weeks prior to beginning treatment on this protocol
• Congestive heart failure \< 6 months prior to screening
• Unstable angina pectoris \< 6 months prior to screening
• Myocardial infarction \< 6 months prior to screening
• Related to recipient (sibling, parent, offspring, offspring of a sibling)
• HLA-haploidentical to recipient (need not be re-tested if already performed previously, provided copies of the original results are available)
• Able and willing to undergo apheresis
• Willing to donate blood for baseline chimerism assessment
• 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)
• Donor must meet institutional eligibility criteria for allogeneic blood stem cell donation including infectious disease screening panel (Hepatitis B, Hepatitis C, HIV, CMV, and West Nile Virus) and CBC, differential and platelet studies
• Donor must meet stem cell donor eligibility criteria as set forth in 21 CFR 1271 subpart C
• 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 o 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
• Active infection (defined as on antimicrobial therapy and/or febrile)

Sponsors & Collaborators

• Altor BioScience: lead
• M.D. Anderson Cancer Center: collaborator

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia

Interventions

Granulocyte Colony-Stimulating Factor; Cytarabine; fludarabine; Cell Count; ALT-801

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cell Physiological Phenomena

Study Officials

• Hing C Wong, PhD

  Altor BioScience

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2011
• First Posted: November 23, 2011
• Study Start: November 1, 2011
• Primary Completion: October 1, 2013
• Study Completion: November 1, 2013
• Last Updated: January 3, 2014

Record last verified: 2014-01

Locations

US (1)