FT538 in Combination With Daratumumab in AML Acute Myeloid Leukemia

NCT04714372 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2020LS114MT2020-33
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase I open-label dose escalation study is conducted in two stages with a primary endpoint to identify the maximum tolerated dose (MTD) of FT538 when administered with daratumumab in patients 12 years and older with advanced acute myeloid leukemia (AML) and related myeloid diseases.

Conditions

Acute Myeloid Leukemia; Myeloid Leukemia; Monocytic Leukemia

Keywords

FT538, AML, Daratumumab, CD38

Outcome Measures

Primary Outcomes (1)

• Number of Participants Experiencing Dose Limiting Toxicity (DLT) Events

  Dose limiting toxicity (DLT) is defined as any AE (based on CTCAE v5) that is at least possibly related to FT538 that occurs after the first FT538 infusion through the end of the DLT assessment period on Day 29 as defined below: Any Grade 4 non-hematologic AE, Grade 3 pulmonary or cardiac AE of any duration, Grade 3 immune cell associated neurotoxicity syndrome (ICANS) of any duration, Any other Grade 3 non-hematologic AE of \>72 hours duration or Grade ≥2 acute GvHD requiring systemic steroid administration

  42 days from the 1st FT538 infusion

Secondary Outcomes (5)

• Number of Participants Achieving Complete Remission (CR + CRi)

  28 days from the 1st FT538 infusion

• Overall Response Rate

  12 months from the 1st FT538 infusion

• Percentage of Participants With Progression Free Survival (PFS)

  12 months from the 1st FT538 infusion

• Percentage of Participants With Overall Survival (OS)

  12 months from the 1st FT538 infusion

• Number of Participants Experiencing Adverse Events

  12 months from the 1st FT538 infusion

Study Arms (4)

Dose Level 1: FT538 at 1 x10^8 cells/dose

EXPERIMENTAL

FT538 administered at assigned dose as an IV infusion via gravity on Day 1, Day 8, and Day 15

Drug: Daratumumab/rHuPH20; Drug: FT538; Drug: Fludarabine; Drug: Cyclophosphamide

Dose Level 2: FT538 at 3 x10^8 cells/dose

EXPERIMENTAL

FT538 administered at assigned dose as an IV infusion via gravity on Day 1, Day 8, and Day 15

Drug: Daratumumab/rHuPH20; Drug: FT538; Drug: Fludarabine; Drug: Cyclophosphamide

Dose Level 3: FT538 at 1 x10^9 cells/dose

EXPERIMENTAL

FT538 administered at assigned dose as an IV infusion via gravity on Day 1, Day 8, and Day 15

Drug: Daratumumab/rHuPH20; Drug: FT538; Drug: Fludarabine; Drug: Cyclophosphamide

Dose Level 4: FT538 at 1.5 x10^9 cells/dose

EXPERIMENTAL

FT538 administered at assigned dose as an IV infusion via gravity on Day 1, Day 8, and Day 15

Drug: Daratumumab/rHuPH20; Drug: FT538; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

Daratumumab/rHuPH20 DRUG

Daratumumab 1800 mg co-formulated with 30,000 units of hyaluronidase (rHuPH20) given subcutaneously into subcutaneous tissue of the abdomen approximately 3 inches \[7.5 cm\] to the right or left of the navel over approximately 3-5 minutes on Day -12 and Day -5 prior to the 1st FT538 infusion, and on Day +3, Day+10, and Day+17 approximately 48 hours after each FT538 infusion.

Also known as: Darzalex

Dose Level 1: FT538 at 1 x10^8 cells/dose; Dose Level 2: FT538 at 3 x10^8 cells/dose; Dose Level 3: FT538 at 1 x10^9 cells/dose; Dose Level 4: FT538 at 1.5 x10^9 cells/dose

FT538 DRUG

FT538 is administered as an IV infusion via gravity using an IV administration set with an in-line filter at the patient's assigned dose levels (DL) on Day 1, Day 8, and Day 15

Dose Level 1: FT538 at 1 x10^8 cells/dose; Dose Level 2: FT538 at 3 x10^8 cells/dose; Dose Level 3: FT538 at 1 x10^9 cells/dose; Dose Level 4: FT538 at 1.5 x10^9 cells/dose

Fludarabine DRUG

Fludarabine 25 mg/m\^2 is administered as a 1 hour intravenous (IV) infusion per institutional guidelines once a day on 2 consecutive days (Day -4, and Day -3).

Also known as: FLUDARA

Dose Level 1: FT538 at 1 x10^8 cells/dose; Dose Level 2: FT538 at 3 x10^8 cells/dose; Dose Level 3: FT538 at 1 x10^9 cells/dose; Dose Level 4: FT538 at 1.5 x10^9 cells/dose

Cyclophosphamide DRUG

Cyclophosphamide 300 mg/m\^2 is administered as a 2 hour intravenous (IV) infusion per institutional guidelines once a day on the same days that fludarabine is given.

Also known as: CYTOXAN, NEOSAR

Dose Level 1: FT538 at 1 x10^8 cells/dose; Dose Level 2: FT538 at 3 x10^8 cells/dose; Dose Level 3: FT538 at 1 x10^9 cells/dose; Dose Level 4: FT538 at 1.5 x10^9 cells/dose

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Acute myeloid leukemia relapsed/refractory after 2 lines of therapy; with CD38 expression
• CD38 expression is defined by ≥20% of malignant cells with CD38 expression by flow cytometry on the most recent marrow biopsy (within 30 days of enrollment - archived or fresh).
• Relapsed/refractory is defined as failure to achieve at least a Morphological Leukemia Free State (MLFS) or reverting from MLFS.
• Lines of therapy are defined as (must have had 2 prior therapies):
• One cycle of Intensive induction chemotherapy such as 7+3, 5+2, MEC, FLAG, FLAG-Ida, CLAG ± small molecule inhibitor
• Four weeks of HMA-based induction ± small molecule inhibitor
• Hematopoietic stem cell transplantation (HSCT) if relapse that occurs \> 90 days after HSCT
• Gemtuzumab Ozogamicin
• LDAC + glasdegib
• Biomarker-specific targeted agents (FLT3 inhibitors, IDH1/2 inhibitors, others if available)
• Other treatments could be considered after discussion with the PI
• Age 12 years or older at the time of consent - Please note, enrollment of minors will be begin until permission to proceed is received from the FDA. At that time, the protocol will be updated to open enrollment to minors.
• Weight ≥ 50 kg due to FT538 fixed cell dosing and FT538 product pre-dose packaging
• Karnofsky performance status of 80-100% for 16 years and older or Lansky Play Score of 80-100 for ≥12 and \< 16 years of age
• Evidence of adequate organ function within 14 days of starting study treatment defined as:

You may not qualify if:

• Diagnosis of acute promyelocytic leukemia (APL)
• Pregnant or breastfeeding, Menstruating females of child-bearing potential must have a negative pregnancy test within 14 days of study treatment start
• Known allergy to any of study drugs or their components
• Clinically significant cardiovascular disease including any of the following: myocardial infarction within 6 months prior to first study treatment; unstable angina or congestive heart failure of New York Heart Association Grade 2 or higher or cardiac ejection fraction \<40%
• Any known condition that requires systemic immunosuppressive therapy (\> 5mg prednisone daily or equivalent) during the FT538 dosing period (3 days before the 1st dose through 14 days after the last dose) excluding pre-medications - inhaled and topical steroids are permitted
• Receipt of any biological therapy, chemotherapy, or radiation therapy, except for palliative purposes, within 2 weeks prior to Day 1 or five half-lives, whichever is shorter; or any investigational therapy within 28 days prior to the to the first dose of daratumumab. Maintenance hydroxyurea for blast control up to the initiation of lympho-conditioning is permitted
• Known active central nervous system (CNS) involvement or treated CNS disease that has not cleared. If prior disease related CNS involvement must have completed effective treatment of their CNS disease at least 2 months prior to Day 1 with no evidence of disease clinically and at least stable findings on relevant CNS imaging
• Non-malignant CNS disease such as epilepsy, CNS vasculitis, or neurodegenerative disease or receipt of medications for these conditions in the 2-year period leading up to study enrollment
• Clinically significant untreated/uncontrolled infection
• Live vaccine \<6 weeks prior to start of lympho-conditioning
• Known seropositive for HIV or known active Hepatitis B or C infection with detectable viral load by PCR
• Prior solid organ transplant
• Allogeneic HSCT relapse occurring \<90 days after HSCT
• Active graft-versus-host-disease (GvHD) requiring systemic immunosuppression within 14 days prior to enrollment
• Presence of any medical or social issues that are likely to interfere with study conduct or may cause increased risk to the participant.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myeloid; Leukemia, Monocytic, Acute

Interventions

daratumumab; fludarabine; fludarabine phosphate; Cyclophosphamide

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Dr. Joseph Maakaron
• Organization: University of Minnesota, Masonic Cancer Center

maaka001@umn.edu

612-624-5109

Study Officials

• Joseph Maakaron, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is performed in two stages, with Stage 1 having two potential steps. A minimum of 28 days separates each patient cohort. Stage 1 step 1 uses a fast-track design (1 patient per cohort) starting at Dose Level 1. The study moves to Stage 1 Step 2 when a pre-defined adverse event occurs during fast-track enrollment, specifically, any Grade 3 non-hematologic event within 72 hours after an FT538 infusion. The cohort size increases from 1 to 3 patients with 2 additional patients added to the current cohort if the event being a Dose Limiting Toxicity (DLT) event. No intra-cohort staggering is required. Escalation in Step 2 continues until the 1st DLT event at which point Stage 2 (CRM) is activated. Stage 2 follows Continual Reassessment Method (CRM) and is initiated at the 1st DLT

Study Record Dates

• First Submitted: January 14, 2021
• First Posted: January 19, 2021
• Study Start: November 3, 2021
• Primary Completion: January 9, 2024
• Study Completion: October 15, 2024
• Last Updated: October 24, 2024
• Results First Posted: October 24, 2024

Record last verified: 2024-10

Locations

US (1)