Clinical trial NCT03301597: NLA101 in Adults Receiving High Dose Chemotherapy for AML
Official title: A Phase 2 Open-Label, Multi-Center, Randomized, Controlled, Dose-Finding Study of NLA101 in Adults Receiving High Dose Chemotherapy for Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Leukemia, Myeloid, Acute
Keywords: Chemotherapy-induced Neutropenia
Bacterial Infections
Fungal Infections
Lead sponsor: Nohla Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2017-10-04
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be randomized to 1 of 3 Investigational Arms or a Control Arm in a 1:1:1:1 ratio.
Primary purpose: PREVENTION

Brief summary: Phase 2 open-label, multi-center, randomized, controlled, dose-finding study of safety and efficacy of NLA101 to reduce the rate of infections associated with CIN in adult subjects with AML.

Detailed description: Phase 2 open-label, multi-center, randomized, controlled, dose-finding study of safety and efficacy of NLA101 to reduce the rate of infections associated with chemotherapy induced neutropenia (CIN) in adult subjects with AML.

Eligible subjects with untreated de novo or secondary AML and per local institutional standards planned to receive at least two cycles of chemotherapy with curative intent will be enrolled into the study and randomized 1:1:1:1 to 1 of 3 Investigational Arms (Standard of Care \[SOC\] chemotherapy + low, medium, or high dose NLA101) or a Control Arm (SOC chemotherapy).

Subjects randomized to an Investigational Arm will be eligible to receive a single fixed assigned dose of NLA101 after the first cycle of chemotherapy, and up to 2 additional identical cell doses after subsequent chemotherapy cycles (one NLA101 infusion per cycle). Subjects randomized to the Control Arm will be followed for up to 3 cycles of chemotherapy.

All subjects will be followed for 84 days following randomization, or 30 days post final infusion of NLA101, or 30 days post the day after the last chemotherapy infusion for Control Arm, whichever is longer.

Eligibility criteria: Key Criteria:

Inclusion Criteria:

* Age ≥ 18 (or legal age of majority for sites outside US).
* Untreated de novo or secondary acute myeloid leukemia (AML), including AML that has progressed from myelodysplastic syndrome (MDS), and histologically documented diagnosis
* Eligible for at least 2 cycles of standard of care AML chemotherapy that will result in moderate to severe myelosuppression and have curative intent
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 or Karnofsky Status of 50 to 100.
* Adequate cardiac, renal, and hepatic functions.

Exclusion Criteria:

* Extramedullary disease in the absence of bone marrow or blood involvement
* Acute promyelocytic leukemia (APL) with PML-RARA
* Prior AML therapy, with the exception of intrathecal chemotherapy or emergent radiation for myeloid sarcoma.
* Concurrent malignancy requiring active treatment with chemotherapy, immunotherapy, or radiation
* Prior allotransplant, including allogeneic hematopoietic cell transplant or solid organ allogeneic transplant
* Known hypersensitivity or history of hypersensitivity to dimethylsulfoxide (DMSO)
* Active/chronic human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) infection

Primary outcomes:
measure: Recurrent Event Rate of Grade 3 or Higher Bacterial or Fungal Infection
timeFrame: From randomization through follow-up of 84 days post randomization, 30 days post last infusion of NLA101, or 30 days post last infusion of chemotherapy for Control Arm, whichever is later
Secondary outcomes:
measure: Event rate of grade 3 or higher documented bacterial and fungal infections per cycle of chemotherapy
timeFrame: From randomization through follow-up of 84 days post randomization, 30 days post last infusion of NLA101, or 30 days post last infusion of chemotherapy for Control Arm, whichever is later
measure: Incidence and duration of filgrastim (or biosimilar) administration
timeFrame: From randomization through follow-up of 84 days post randomization, 30 days post last infusion of NLA101, or 30 days post last infusion of chemotherapy for Control Arm, whichever is later
measure: Overall Response Rate
timeFrame: From randomization through follow-up of 84 days post randomization, 30 days post last infusion of NLA101, or 30 days post last infusion of chemotherapy for Control Arm, whichever is later
measure: Incidence and duration of complications due to infections
timeFrame: From randomization through follow-up of 84 days post randomization, 30 days post last infusion of NLA101, or 30 days post last infusion of chemotherapy for Control Arm, whichever is later
measure: Incidence and duration of febrile neutropenia
timeFrame: From randomization through follow-up of 84 days post randomization, 30 days post last infusion of NLA101, or 30 days post last infusion of chemotherapy for Control Arm, whichever is later
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Louisville
country: United States
facility: Norton Cancer Institute, St. Matthews Campus
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center - Fred & Pamela Buffett Cancer Center
state: Nebraska
city: Hawthorne
country: United States
facility: Westchester Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College - NewYork-Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai and Mount Sinai Health System
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University
state: New York
city: Durham
country: United States
facility: Duke University Heath System, Duke Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Danville
country: United States
facility: Geisinger Medical Center
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
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert Hospital and The Medical College of Wisconsin
state: Wisconsin
city: Darlinghurst
country: Australia
facility: St. Vincent's Hospital Sydney
state: New South Wales
city: Kogarah
country: Australia
facility: St. George Hospital
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Richmond
country: Australia
facility: Epworth HealthCare
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea's Seoul St. Mary's Hospital
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Martin S Tallman, MD
role: STUDY_CHAIR
affiliation: M.D. Anderson Cancer Center
name: Naval G Daver, MD
role: STUDY_CHAIR
References: