NCT02890758

Phase I Trial of Universal Donor NK Cell Therapy in Combination With ALT803

Phase I Trial of Universal Donor NK Cell Therapy in Combination With ALT-803

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: Brenda Cooper, MD · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to find the number of natural killer (NK) cells from non-HLA matched donors that can be safely infused into patients with cancer. NK cells are a form of lymphocytes that defend against cancer cells. NK cells in cancer patients do not work well to fight cancer. In this study, the NK cells are being donated by healthy individuals without cancer who are not "matched" by human leukocyte antigen (HLA) genes to patients. After receiving these NK cells, patients may also be given a drug called ALT803. ALT803 is a protein that keeps NK cells alive, helps them grow in number and supports their cancer-fighting characteristics. HLA-unmatched NK cell infusion is investigational (experimental) because the process has not approved by the Food and Drug Administration (FDA).

Detailed description

Primary Objective: To determine the maximum tolerated dose (MTD) of ex vivo expanded non-HLA matched donor NK cells in combination with ALT-803 Secondary Objectives: * Describe safety profile / toxicity of combining ALT-803 with NK cell adoptive therapy. * Determine antitumor activity of allogeneic NK cells with ALT-803 support. * Determine if a lymphocyte depleting regimen is adequate for preventing early elimination of HLA-mismatched donor NK cells by host T-cells. Study Design: This is a phase I study with "3+3" design with three planned dose levels of NK cells and a fixed dose of ALT-803. Three patients will be enrolled sequentially to each dose level, starting with dose level 1. Patients will be segregated to either receive ALT803 as cytokine support after NK cell infusion (starting with same dose level as Level 1) or no cytokine administration. Patients in the arm receiving ALT803 will be either hematologic malignancy patients (Cohort A) or Colon/Soft tissue sarcoma patients (Cohort B). Absence of dose limiting toxicity (DLT) in the DLT assessment period of 28 days must be documented for all patients enrolled a cell dose without ALT803 before the next cohort of patients to receive cytokines at that dose level can be enrolled. Patients can also be enrolled in parallel to the next cell dose level without cytokines.

Conditions

• Acute Myeloid Leukemia
• Myelodysplastic Syndrome
• Acute Lymphoblastic Leukemia
• Chronic Myeloid Leukemia
• Chronic Lymphocytic Leukemia
• Non Hodgkin Lymphoma
• Hodgkin Lymphoma
• Myeloproliferative Syndromes
• Plasma Cell Myeloma
• Colon Carcinoma
• Adenocarcinoma of Rectum
• Soft Tissue Sarcoma
• Ewing's Sarcoma
• Rhabdomyosarcoma

Interventions

Type	Name	Description
BIOLOGICAL	Natural Killer (NK) Cells	Dose escalation of Natural Killer (NK) Cells from two infusion of starting at Dose Level 1 (1x10\^7 cells/kg), dose Level-1 (1x10\^6 cells/kg) if 2 of 6 patients at Level 1 develop DLTs. Escalation to dose level 2 (2.5X10\^7) and Dose level 3 (5X10\^7) is dependent on DLT
BIOLOGICAL	ALT803	given at 6mcg/kg weekly for four weeks

Timeline

• Start date: 2018-05-22
• Primary completion: 2021-06-01
• Completion: 2023-02-17
• First posted: 2016-09-07
• Last updated: 2023-02-21

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study