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

NCT02890758 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CASE2Z16
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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).

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

Keywords

Natural Killer Cell; ALT-803

Outcome Measures

Primary Outcomes (2)

• MTD of ex vivo expanded non-HLA matched donor NK cells in combination with ALT-803

  MTD Will be determined by dose limiting toxicity (DLT). The MTD will be defined as the dose level immediately below that at which 2 of 6 subjects experience a dose limiting toxicity.

  Up to 28 days

• Number of participants without Graft Versus Host Disease (GVHD)

  Measure of safety of natural killer (NK) cells in the absence of HLA matching

  up to 28 days after beginning treatment

Secondary Outcomes (12)

• Number of patients with hematological response

  Up to 12 months after beginning treatment

• Patients response for radiographically measurable lesions

  Up to 12 months after beginning treatment

• Patients with malignant lymphoma response

  Up to 12 months after beginning treatment

• Patients response for Waldenstrom's macroglobulinemia (WM)

  Up to 12 months after beginning treatment

• Patients response for cutaneous lymphomas

  Up to 12 months after beginning treatment

Study Arms (2)

Cytokine Arm

EXPERIMENTAL

Two infusions of Natural Killer (NK) cells and ALT803

Biological: Natural Killer (NK) Cells; Biological: ALT803

No Cytokine Arm

ACTIVE COMPARATOR

Two infusions of Natural Killer (NK) Cells

Biological: Natural Killer (NK) Cells

Interventions

Natural Killer (NK) Cells BIOLOGICAL

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

Cytokine Arm; No Cytokine Arm

ALT803 BIOLOGICAL

given at 6mcg/kg weekly for four weeks

Also known as: Cytokine

Cytokine Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologic confirmation of relapsed and or refractory hematologic malignancy, locally advanced or metastatic colon/rectal carcinoma, or refractory and/or relapsed soft tissue sarcomas and have failed at least one standard line of therapy.
• Patients will be eligible if they have either declined standard treatment regimens or if there is no standard approach to curative salvage therapy per National Comprehensive Cancer Network (NCCN) guidelines in the setting of relapsed/refractory disease.
• In addition, patients for whom a potential 29-day delay in treatment will not interfere with the subject's potential therapeutic options can be eligible per the treating physician's discretion.
• Malignancies can include:
• 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/rectal carcinoma
• Soft tissue sarcomas including but not limited to Ewing's sarcoma and Rhabdomyosarcoma

You may not qualify if:

• Subjects receiving any other investigational agents.
• Subjects for whom a potential 29-day delay in treatment will interfere with the subject's potential therapeutic options.
• Patients with untreated malignant involvement of the central nervous system (CNS) should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Head imaging will be necessary to document absence of CNS involvement in patients with colon/rectal cancer and soft tissue sarcomas. Patients with hematologic malignancies who have undergone treatment for malignant involvement of the CNS must have no evidence of residual disease by imaging or CSF sampling prior to study enrollment.
• History of allergic reactions to chemotherapy agents used in this protocol as part of lymphodepletion regimen (Fludarabine and Cyclophosphamide)
• Patients with uncontrolled intercurrent illness including, but not limited to ongoing active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or breastfeeding women are excluded from this study.
• HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with chemotherapeutic agents. In addition, these patients are at increased risk of lethal infections when treated with marrow suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
• Chronic active untreated hepatitis B or C infection.
• Recipients of previous allogeneic transplants who have rash involving more than 10% body surface area attributed to graft versus host disease (GVHD) (\> Grade 1 GVHD of skin). Stem cell transplant recipients will be excluded if they are still receiving immunosuppression including steroids for GVHD or have active GVHD in any organ (except for Grade 1 only of skin, not requiring treatment).

Sponsors & Collaborators

• Brenda Cooper, MD: lead

Study Sites (1)

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Hodgkin Disease; Multiple Myeloma; Colonic Neoplasms; Rectal Neoplasms; Sarcoma; Sarcoma, Ewing; Rhabdomyosarcoma

Interventions

Cell Count; ALT-803; Cytokines

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, B-Cell; Lymphoma; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplasms, Connective and Soft Tissue; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Myosarcoma; Neoplasms, Muscle Tissue

Intervention Hierarchy (Ancestors)

Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cell Physiological Phenomena; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• David Wald, MD, PhD

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Oncology Specialist

Study Record Dates

• First Submitted: September 1, 2016
• First Posted: September 7, 2016
• Study Start: May 22, 2018
• Primary Completion: June 1, 2021
• Study Completion: February 17, 2023
• Last Updated: February 21, 2023

Record last verified: 2023-02

Locations

US (1)