NLA101 in Adults Receiving High Dose Chemotherapy for AML

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 2 Open-Label, Multi-Center, Randomized, Controlled, Dose-Finding Study of NLA101 in Adults Receiving High Dose Chemotherapy for Acute Myeloid Leukemia

Conditions
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Leukemia, Myeloid, Acute

Intervention / Treatment
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* Biological: NLA101
* Drug: Standard of Care (SOC) chemotherapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be randomized to 1 of 3 Investigational Arms or a Control Arm in a 1:1:1:1 ratio.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Control Arm<br>The Control Arm will receive standard of care (SOC) chemotherapy without the infusion of NLA101. SOC chemotherapy will be determined by local PI and must be a standard regimen for untreated de novo or secondary AML that will result in moderate to severe myelosuppression and will be given with curative intent. | Drug: Standard of Care (SOC) chemotherapy<br>* The SOC chemotherapy regimen for each patient will be determined by local PI. Regimen must be a standard AML regimen that will result in moderate to severe myelosuppression and have curative intent.<br>|
| Experimental: Low Dose Arm<br>The Low Dose Arm will receive standard of care (SOC) chemotherapy with the infusion of low-dose NLA101. | Biological: NLA101<br>* NLA101 is a universal donor off-the-shelf ex-vivo expanded hematopoietic stem and progenitor cell (HSPC) product that is cryopreserved and ready for immediate use.<br>* Other names: Dilanubicel;Drug: Standard of Care (SOC) chemotherapy<br>* The SOC chemotherapy regimen for each patient will be determined by local PI. Regimen must be a standard AML regimen that will result in moderate to severe myelosuppression and have curative intent.<br>|
| Experimental: Medium Dose Arm<br>The Medium Dose Arm will receive standard of care (SOC) chemotherapy with the infusion of medium-dose NLA101. | Biological: NLA101<br>* NLA101 is a universal donor off-the-shelf ex-vivo expanded hematopoietic stem and progenitor cell (HSPC) product that is cryopreserved and ready for immediate use.<br>* Other names: Dilanubicel;Drug: Standard of Care (SOC) chemotherapy<br>* The SOC chemotherapy regimen for each patient will be determined by local PI. Regimen must be a standard AML regimen that will result in moderate to severe myelosuppression and have curative intent.<br>|
| Experimental: High Dose Arm<br>The High Dose Arm will receive standard of care (SOC) chemotherapy with the infusion of high-dose NLA101. | Biological: NLA101<br>* NLA101 is a universal donor off-the-shelf ex-vivo expanded hematopoietic stem and progenitor cell (HSPC) product that is cryopreserved and ready for immediate use.<br>* Other names: Dilanubicel;Drug: Standard of Care (SOC) chemotherapy<br>* The SOC chemotherapy regimen for each patient will be determined by local PI. Regimen must be a standard AML regimen that will result in moderate to severe myelosuppression and have curative intent.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrent Event Rate of Grade 3 or Higher Bacterial or Fungal Infection |  | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event rate of grade 3 or higher documented bacterial and fungal infections per cycle of chemotherapy |  | 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 | 
| Incidence and duration of filgrastim (or biosimilar) administration |  | 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 | 
| Overall Response Rate |  | 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 | 
| Incidence and duration of complications due to infections |  | 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 | 
| Incidence and duration of febrile neutropenia |  | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chemotherapy-induced Neutropenia, Bacterial Infections, Fungal Infections