Natural Killer Cell (CYNK-001) Infusions in Adults With Multiple Myeloma

NCT04309084 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: CYNK-001-MM-002
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 4

Brief Summary

This study will find the maximum tolerated dose (MTD) of CYNK-001 which contain NK cells derived from human placental CD34+ cells and culture-expanded. CYNK-001 cells will be given post Autologous Stem Cell Transplant (ASCT). The safety of this treatment will be evaluated, and researchers will want to learn if NK cells will help in treating Multiple Myeloma.

Conditions

Multiple Myeloma; Neoplasm, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorder; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Antineoplastic Agents; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs

Keywords

CYNK-001; Autologous stem cell transplant; Cell therapy; NK cells; Natural killer cells; Multiple Myeloma; Plasma Cell Myeloma; Plasma Cell Neoplasm; Newly Diagnosed Multiple Myeloma; Minimal Residual Disease; MRD

Outcome Measures

Primary Outcomes (4)

• Dose-Limiting Toxicity (DLT)

  Safety Assessment of Dose-Limiting Toxicity (DLT)

  Up to 28 days

• Maximum Tolerated Dose (MTD) or Maximum Planned Dose (MPD)

  Safety Assessment of MTD OR MPD

  Up to 28 days

• Adverse Events (AE)

  Safety Assessment of AE's

  Up to 12 months

• Rate of Minimal Residual Disease (MRD) Negativity

  Efficacy Assessment of MRD

  Day 90-100

Secondary Outcomes (8)

• Minimal Residual Disease (MRD) Response

  Day 90-100

• Time to MRD Response

  up to 12 months

• International Myeloma Working Group (IMWG) response

  up to 12 months

• duration of clinical response

  up to 12 months

• Progression-free survival

  up to 12 months

Study Arms (1)

Phase I

EXPERIMENTAL

Up to three dosing cohorts of CYNK-001 given on Day 2 or Days 2, 7, 14 post ASCT. Once MTD has been determined, the Expansion cohort will commence.

Biological: CYNK-001

Interventions

CYNK-001 BIOLOGICAL

CYNK-001 is an allogeneic off the shelf cell therapy enriched for CD56+/CD3- NK cells expanded from human placental CD34+ cells.

Phase I

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must satisfy the following criteria to be enrolled in the study:
• Subject has eligible disease status:
• Newly diagnosed multiple myeloma undergoing or completed induction therapy prior to undergoing first ASCT and presenting MRD positive by NGS after completion of induction therapy.
• Subject is \> 18 and ≤ 75 years of age at the time of signing the informed consent form (ICF).
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Subject is willing and able to adhere to the study schedule and other protocol requirements.
• Performance status of Eastern Cooperative Oncology Group (ECOG) \< 2
• Ability to be off immunosuppressive drugs for at least 3 days prior to the CYNK-001 cell infusion. Steroids at the equivalent of no more than 5 mg prednisone per day are permissible.
• Subjects must have autologous peripheral blood stem cell graft available in storage for additional transplant in the event of engraftment failure.
• Female of childbearing potential (FCBP) must not be pregnant and agree to not becoming pregnant for at least 28 days following the CYNK-001. FCBP must agree to use an adequate method of contraception during the treatment period.
• FCBP is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months).
• Male subjects must agree to use a condom during sexual contact for at least 28 days following the CYNK-001, even if he has undergone a successful vasectomy.

You may not qualify if:

• The presence of any of the following will exclude a subject from enrollment:
• Subject has plasma cell leukemia.
• Subject has non-secretory myeloma.
• Subject has previously undergone allogeneic stem cell transplant.
• Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
• Subject has any condition including the presence of laboratory abnormalities which places the subject at unacceptable risk if he or she were to participate in the study.
• Subject has any condition that confounds the ability to interpret data from the study.
• Subject has a known sensitivity or allergy to lenalidomide which will limit the subject from receiving the mandatory lenalidomide maintenance as part of the study plan.
• Subject has aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase ≥ 2.5 x the upper limit of normal (ULN) within 7 days prior to melphalan administration. Transient abnormalities should be discussed with the medical monitor.
• This eligibility criterion removed with Amendment 1
• Estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m2 at screening calculated using the Modification of Diet in Renal Disease Study equation. (Levey, 2006)
• Subject has a bilirubin level \> 2 mg/dL (unless subject has known Gilbert's disease) at screening.
• Subject has had prior treatment with biologic antineoplastic agents less than 7 days before CYNK-001 infusion and at least 5 half-lives since (excludes melphalan). (Exception will be granted for monoclonal antibodies that are known to have long half-lives, in which case a minimum of 2 weeks from last dose will be required). For agents that have known AEs occurring beyond these specified days after administration, this period must be extended beyond the time during which acute AEs are known to occur. Treating physicians are encouraged to discuss cases with the Medical Monitor.
• Subject is pregnant or breastfeeding.
• Subject has new or progressive pulmonary infiltrates or pleural effusion large enough to be detected by chest x-ray or computerized tomography (CT) scan within 2 weeks of CYNK-001 infusion.

Sponsors & Collaborators

• Celularity Incorporated: lead

Study Sites (4)

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Roswell Park Comprehensive Cancer Institute

Buffalo, New York, 14203, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Related Publications (1)

• Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, Kusek JW, Van Lente F; Chronic Kidney Disease Epidemiology Collaboration. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006 Aug 15;145(4):247-54. doi: 10.7326/0003-4819-145-4-200608150-00004.

  PMID: 16908915 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Neoplasm, Residual

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Lymphatic Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Adrian Kilcoyne, MD

  Celularity Incorporated

  STUDY DIRECTOR

Study Design

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

Model Details: The study will utilize a 3+3 open label design, and will enroll up to three dosing cohorts of CYNK-001 given on Day 2 or Days 2, 7, 14 post ASCT. Once MTD has been determined, the Expansion cohort will commence.

Study Record Dates

• First Submitted: March 12, 2020
• First Posted: March 16, 2020
• Study Start: May 12, 2020
• Primary Completion: January 31, 2023
• Study Completion: April 30, 2023
• Last Updated: February 16, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)