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

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02282215
• Other study ID #: CLT008-03
• Status: Completed
• Phase: Phase 2
• Start date: December 2014
• Est. completion date: September 22, 2017

Study information

• Verified date: September 2018
• Source: Cellerant Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 163
• Est. completion date: September 22, 2017
• Est. primary completion date: September 22, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Infection
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Neutropenia

Intervention

Biological:
• CLT-008
Single intravenous infusion
• G-CSF
Daily subcutaneous injections

Locations

Country	Name	City	State
United States	Northside Hospital	Atlanta	Georgia
United States	Northwestern Medical Faculty Foundation	Chicago	Illinois
United States	The University of Chicago	Chicago	Illinois
United States	University of Illinois Cancer Center	Chicago	Illinois
United States	UF Health Shands Cancer Hospital	Gainesville	Florida
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Indiana Blood and Marrow Transplantation Clinic	Indianapolis	Indiana
United States	Mayo Clinic Florida	Jacksonville	Florida
United States	Kansas City Veterans Affairs Medical Center	Kansas City	Missouri
United States	University of California San Diego Moores Cancer Center	La Jolla	California
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	University of Minnesota Physicians BMT Clinic	Minneapolis	Minnesota
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Weill Cornell Medical College - New York Presbyterian Hospital	New York	New York
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	West Penn Hospital	Pittsburgh	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of California, San Francisco Medical Center	San Francisco	California
United States	Swedish Cancer Institute	Seattle	Washington
United States	Westchester Medical Center	Valhalla	New York
United States	University of Massachusetts Worcester	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Cellerant Therapeutics	Department of Health and Human Services

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of febrile episodes (fever)		42 days
Secondary	Time to absolute neutrophil count (ANC) recovery		42 days
Secondary	Incidence and duration of febrile neutropenia		42 days
Secondary	Incidence and duration of infection		42 days
Secondary	Incidence and severity of mucositis		42 days
Secondary	Incidence of infusion reactions		42 days
Secondary	Incidence of Graft-versus-Host Disease (GVHD)		42 days
Secondary	Incidence of Adverse Events (AE)		42 days
Secondary	Incidence of Serious Adverse Events (SAE)		42 days

External Links

•   Cellerant Therapeutics CLT-008: Myeloid Progenitor Cells