Clinical trial NCT02282215: Safety and Efficacy of Human Myeloid Progenitor Cells (CLT-008) During Chemotherapy for Acute Myeloid Leukemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Neutropenia
Infection
Keywords: Fever
Induction chemotherapy
Infection
Leukemia
Myeloid progenitor cells
Neutropenia
Lead sponsor: Cellerant Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Department of Health and Human Services
First posted: 2014-11-04
Enrollment: 163
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Duration of febrile episodes (fever)
timeFrame: 42 days
Secondary outcomes:
measure: Time to absolute neutrophil count (ANC) recovery
timeFrame: 42 days
measure: Incidence and duration of febrile neutropenia
timeFrame: 42 days
measure: Incidence and duration of infection
timeFrame: 42 days
measure: Incidence and severity of mucositis
timeFrame: 42 days
measure: Incidence of infusion reactions
timeFrame: 42 days
measure: Incidence of Graft-versus-Host Disease (GVHD)
timeFrame: 42 days
measure: Incidence of Adverse Events (AE)
timeFrame: 42 days
measure: Incidence of Serious Adverse Events (SAE)
timeFrame: 42 days
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco Medical Center
state: California
city: Gainesville
country: United States
facility: UF Health Shands Cancer Hospital
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern Medical Faculty Foundation
state: Illinois
city: Chicago
country: United States
facility: University of Illinois Cancer Center
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Blood and Marrow Transplantation Clinic
state: Indiana
city: Worcester
country: United States
facility: University of Massachusetts Worcester
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota Physicians BMT Clinic
state: Minnesota
city: Kansas City
country: United States
facility: Kansas City Veterans Affairs Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Weill Cornell Medical College - New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Valhalla
country: United States
facility: Westchester Medical Center
state: New York
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: West Penn Hospital
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
Study officials:
affiliation: Cellerant Therapeutics
name: William Reed, MD
role: STUDY_DIRECTOR
References:
citation: 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.