Safety and Efficacy of Human Myeloid Progenitor Cells (CLT-008) During Chemotherapy for Acute Myeloid Leukemia

An Open-Label Phase 2 Prospective, Randomized, Controlled Study of CLT-008 Myeloid Progenitor Cells as a Supportive Care Measure During Induction Chemotherapy for Acute Myeloid Leukemia

The purpose of the study is to explore the safety and efficacy of CLT-008 as an extra supportive care measure after induction chemotherapy for patients with acute myeloid leukemia (AML).

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia; Neutropenia; Infection
• Intervention / Treatment: Biological: CLT-008; Biological: G-CSF

Detailed Description

The prolonged period of severe neutropenia caused by induction chemotherapy for the treatment of AML is associated with a nearly universal risk of febrile neutropenia. Standard supportive care strategies include administration of prophylactic anti-bacterial and anti-fungal agents, but serious breakthrough bacterial and fungal infections still occur. Granulocyte colony-stimulating factor (G-CSF; filgrastim, Neupogen®) has been shown to shorten the duration of severe neutropenia, fever, antibiotic use and hospitalization following induction chemotherapy for AML. CLT-008, a human allogeneic myeloid progenitor cell product, is intended to provide the cellular target for G-CSF to produce neutrophils during the period of chemotherapy-induced bone marrow suppression when the patient's own progenitor cells may be limited in responding to G-CSF. It is hypothesized that the production of allogeneic neutrophils from CLT-008 will be sufficient to mitigate the infection-related consequences of induction chemotherapy for AML.

• Study Type: Interventional
• Enrollment (Actual): 163
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • University of California San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center
    • San Francisco, California, United States, 94143
      • University of California, San Francisco Medical Center
  • Florida
    • Gainesville, Florida, United States, 32608
      • UF Health Shands Cancer Hospital
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago
    • Chicago, Illinois, United States, 60612
      • University of Illinois Cancer Center
    • Chicago, Illinois, United States, 60611
      • Northwestern Medical Faculty Foundation
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Indiana Blood and Marrow Transplantation Clinic
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Worcester
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Physicians BMT Clinic
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • Kansas City Veterans Affairs Medical Center
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College - New York Presbyterian Hospital
    • New York, New York, United States, 66215
      • Memorial Sloan Kettering Cancer Center
    • Valhalla, New York, United States, 10595
      • Westchester Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • West Penn Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Acute myeloid leukemia arising de novo (per European LeukemiaNet)

2. Treated with any established chemotherapy regimen based on either:

   1. 7+3: Standard-dose cytarabine 100-200 mg per meter squared continuous infusion for 7 days with idarubicin 12 mg per meter squared or daunorubicin 45-90 mg per meter squared for 3 days
   2. High-dose cytarabine-based (HIDAC) chemotherapy administering a total cytarabine dose of ≥ 4 g per meter squared alone or in combination with other anti-leukemic agents (for example, anthracyclines, purine nucleoside inhibitors, etoposide, etc.)
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at Screening or by the day chemotherapy is initiated
4. Adequate respiratory function with a room air oxygen saturation of at least 92%
5. Adequate cardiac function defined as an ejection fraction of at least 45%
6. Serum bilirubin ≤ 1.5 times the upper limits of normal. Subjects with a history of Gilbert's syndrome may be enrolled if the total bilirubin is < 3 mg/dL with an indirect bilirubin of > 1.5 mg/dL
7. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times upper limits of normal prior to chemotherapy
8. Serum creatinine ≤ 2 times upper limits of normal or estimated glomerular filtration rate ≥ 60 mL/min/1.73 meter squared per Modification of Diet in Renal Disease equation (MDRD)
9. All subjects, except post-menopausal women, must be willing to utilize a highly effective method of contraception throughout the study
10. Adequately informed of the nature and risks of the study with written informed consent

Exclusion Criteria:

1. Pregnant or breast feeding
2. Overt central nervous system manifestations of leukemia at diagnosis
3. Specifically diagnosed and uncontrolled fungal, bacterial, viral, or other infection (e.g. confirmed sepsis, pneumonia, abscess, cellulitis, etc.) at the day chemotherapy is initiated. "Uncontrolled" is defined as exhibiting ongoing signs and symptoms of infection without improvement despite antimicrobial or other treatment.
4. AML subtype M3 (promyelocytic leukemia)
5. Previous chemotherapy for AML
6. History of or current human immunodeficiency virus (HIV) or hepatitis C virus infection
7. History of or current clinically significant immunodeficiency
8. Known contraindication to receiving G-CSF
9. History of or current clinically significant alloimmunization to leukocyte antigens
10. Participation in another clinical study within 28 days of the day chemotherapy is initiated, in which the study drug or device may influence hematopoiesis. Co-enrollment in another study is allowed in cases where the investigational therapy under study is a version of an acceptable chemotherapy regimen for this study per the inclusion criteria.
11. Receiving any agent concurrently with CLT-008 infusion which inhibits cell division (e.g., methotrexate or hydroxyurea)
12. Acute or chronic medical disorder that, in the opinion of the investigator or medical monitor, may prevent the subject from completing participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CLT-008 low dose with G-CSF; Dose escalation	Biological: CLT-008; Single intravenous infusion; Other Names: human allogeneic myeloid progenitor cells (hMPC); romyelocel-L; Biological: G-CSF; Daily subcutaneous injections; Other Names: Zarxio; granulocyte colony-stimulating factor; Granix (tbo-filgrastim); Neupogen (filgrastim)
Experimental: CLT-008 high dose with G-CSF; Dose escalation	Biological: CLT-008; Single intravenous infusion; Other Names: human allogeneic myeloid progenitor cells (hMPC); romyelocel-L; Biological: G-CSF; Daily subcutaneous injections; Other Names: Zarxio; granulocyte colony-stimulating factor; Granix (tbo-filgrastim); Neupogen (filgrastim)
Experimental: CLT-008 with G-CSF; Randomized	Biological: CLT-008; Single intravenous infusion; Other Names: human allogeneic myeloid progenitor cells (hMPC); romyelocel-L; Biological: G-CSF; Daily subcutaneous injections; Other Names: Zarxio; granulocyte colony-stimulating factor; Granix (tbo-filgrastim); Neupogen (filgrastim)
Active Comparator: G-CSF; Randomized	Biological: G-CSF; Daily subcutaneous injections; Other Names: Zarxio; granulocyte colony-stimulating factor; Granix (tbo-filgrastim); Neupogen (filgrastim)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Duration of febrile episodes (fever)	42 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to absolute neutrophil count (ANC) recovery	42 days
Incidence and duration of febrile neutropenia	42 days
Incidence and duration of infection	42 days
Incidence and severity of mucositis	42 days
Incidence of infusion reactions	42 days
Incidence of Graft-versus-Host Disease (GVHD)	42 days
Incidence of Adverse Events (AE)	42 days
Incidence of Serious Adverse Events (SAE)	42 days

Collaborators and Investigators

• Sponsor: Cellerant Therapeutics
• Collaborators: Department of Health and Human Services
• Investigators: Study Director: William Reed, MD, Cellerant Therapeutics

Publications and helpful links

General Publications

• Desai PM, Brown J, Gill S, Solh MM, Akard LP, Hsu JW, Ustun C, Andreadis C, Frankfurt O, Foran JM, Lister J, Schiller GJ, Wieduwilt MJ, Pagel JM, Stiff PJ, Liu D, Khan I, Stock W, Kambhampati S, Tallman MS, Morris L, Edwards J, Pusic I, Kantarjian HM, Mamelok R, Wong A, Van Syoc R, Kellerman L, Panuganti S, Mandalam R, Abboud CN, Ravandi F. Open-Label Phase II Prospective, Randomized, Controlled Study of Romyelocel-L Myeloid Progenitor Cells to Reduce Infection During Induction Chemotherapy for Acute Myeloid Leukemia. J Clin Oncol. 2021 Oct 10;39(29):3261-3272. doi: 10.1200/JCO.20.01739. Epub 2021 Jun 22.

Helpful Links

• Cellerant Therapeutics CLT-008: Myeloid Progenitor Cells

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2014
• Primary Completion (Actual): September 22, 2017
• Study Completion (Actual): September 22, 2017

Study Registration Dates

• First Submitted: October 31, 2014
• First Submitted That Met QC Criteria: October 31, 2014
• First Posted (Estimate): November 4, 2014

Study Record Updates

• Last Update Posted (Actual): September 27, 2018
• Last Update Submitted That Met QC Criteria: September 25, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Infection; Fever; Leukemia; Neutropenia; Induction chemotherapy; Myeloid progenitor cells
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Agranulocytosis; Leukopenia; Leukocyte Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neutropenia; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Lenograstim
• Other Study ID Numbers: CLT008-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided