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Acute Myeloid LeukemiaPhase 1NCT04714372

FT538 in Combination With Daratumumab in AML Acute Myeloid Leukemia

A Phase 1 study testing Daratumumab/rHuPH20, FT538 and Fludarabine in people with Acute Myeloid Leukemia and Myeloid Leukemia, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 12 years and older
What is being tested?
Daratumumab/rHuPH20, FT538 and Fludarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
3 Nov 2021to 15 Oct 2024
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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:
  • Estimated Glomerular Filtration Rate (estimated creatinine clearance) ≥50 mL/min/1.73m^2
  • Total bilirubin ≤ 5 × upper limit normal (ULN), not applicable for patients with Gilbert's syndrome
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  • AST ≤3 × ULN and ALT ≤ 3 × ULN, not applicable if determined to be directly due to underlying malignancy
  • LVEF ≥ 40% by echocardiogram or MUGA
  • Contraceptive use by men or women
  • Female subjects: Women of childbearing potential (WOCBP) must use a highly effective form of contraception from the screening visit until at least 12 months after the final dose of cyclophosphamide (CY), at least 4 months after the final dose of FT538, and at least 3 months after the final dose of daratumumab, whichever is latest.
  • Male subjects: Males with a female partner of childbearing potential or a pregnant female partner must be sterile (biologically or surgically) or use a highly effective method of contraception from the screening visit until at least 4 months after the final dose of CY and at least 4 months after the final dose of FT538, and at least 3 months after the final dose of daratumumab, whichever is latest.
  • Must agree to and sign the consent for the companion Long-Term Follow-Up study (UMN CPRC #2020LS166) to fulfill the FDA required 15 years of follow-up for a genetically modified cell product.
  • Must agree to and sign the consent for the companion Long-Term Follow-Up study (UMN CPRC #2020LS166) to fulfill the FDA required 15 years of follow-up for a genetically modified cell product.

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Masonic Cancer Center, University of Minnesota

    Minneapolis, Minnesota, 55455

Other trials in United States

About this study

Official title: Study of FT538 in Combination With Daratumumab in Acute Myeloid Leukemia

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.

Read the detailed description

FT538 is an off the shelf product comprised of allogeneic natural killer (NK)-cell immunotherapy lacking CD38 and expressing hnCD16 and IL-15RF. Daratumumab is a targeted therapy (IgG1k human monoclonal antibody) that targets CD38.

FT538 is administered once a week for 3 consecutive weeks (Day 1, Day 8, and Day 15). Up to 5 dose levels will be tested. Fixed dose subcutaneous daratumumab is given on Day -12 and Day 5 prior to the NK cells as lymphodepletion, and on Day +3, Day +10, and Day +17 to maximize targeting. A short course of outpatient lymphodepleting chemotherapy is given on Day -4 and Day -3 to promote adoptive transfer. Day 1, the day of the 1st FT538 infusion, must be a Monday.

The primary analysis for Phase I is intent-to-treat in that all patients receiving the 1st infusion of FT538 are evaluable for toxicity and efficacy. Patients who discontinue therapy prior to the first FT538 will be replaced.

There are five potential FT538 dose cohorts. The starting dose is FT538 1x10e8 cells per dose with a lower safety dose of 5x10e7 if needed (Dose Level -1). The subsequent planned FT538 cohorts are 3x10e8, 1x10e9, and 1.5 x10e9 FT538 cells per dose. Dosing is based on hnCD16 expression, where 90% ± 10% of administered FT538 cells express hnCD16. The trial is conducted with no intra-patient escalation.

Being tested
Daratumumab/rHuPH20, FT538, Fludarabine, Cyclophosphamide
Keywords
FT538, AML, Daratumumab, CD38
Medical subject headings
Leukemia, Myeloid, Acute, Leukemia, Myeloid, Leukemia, Monocytic, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Daratumumab/rHuPH20Drug

    Also called Darzalex

    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.

  • FT538Drug

    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

  • FludarabineDrug

    Also called FLUDARA

    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).

  • CyclophosphamideDrug

    Also called CYTOXAN, NEOSAR

    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.

Study groups in NCT04714372
Study groupRoleWhat they receive
Dose Level 1: FT538 at 1 x10^8 cells/doseExperimentalFT538 administered at assigned dose as an IV infusion via gravity on Day 1, Day 8, and Day 15
Receives: Drug: Daratumumab/rHuPH20; Drug: FT538; Drug: Fludarabine; Drug: Cyclophosphamide
Dose Level 2: FT538 at 3 x10^8 cells/doseExperimentalFT538 administered at assigned dose as an IV infusion via gravity on Day 1, Day 8, and Day 15
Receives: Drug: Daratumumab/rHuPH20; Drug: FT538; Drug: Fludarabine; Drug: Cyclophosphamide
Dose Level 3: FT538 at 1 x10^9 cells/doseExperimentalFT538 administered at assigned dose as an IV infusion via gravity on Day 1, Day 8, and Day 15
Receives: Drug: Daratumumab/rHuPH20; Drug: FT538; Drug: Fludarabine; Drug: Cyclophosphamide
Dose Level 4: FT538 at 1.5 x10^9 cells/doseExperimentalFT538 administered at assigned dose as an IV infusion via gravity on Day 1, Day 8, and Day 15
Receives: Drug: Daratumumab/rHuPH20; Drug: FT538; Drug: Fludarabine; Drug: Cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 42 days from the 1st FT538 infusion

Secondary outcomes (5)
  1. Number of Participants Achieving Complete Remission (CR + CRi)

    Efficacy of treatment is measured by the objective response rate (Complete Remission [CR] + Complete Remission with Incomplete Hematologic Recovery [CRi]) assessed by Day 28 based on the 2017 European LeukemiaNet (ELN) response criteria CR - defined as bone marrow blast <5%, absence of circulating blasts and blasts with auer rods, absence of extramedullary disease, Absolute neutrophil count >= 1.0 × 10e9/L (1000/μL) and platelet count >=100 × 10e9/L 100,000/μL) CRi - defined as all CR criterial except for residual neutropenia (<1.0 × 10e9/L [1000/μL]) or thrombocytopenia (<100 × 10e9/L [100,000/μL])

    Measured: 28 days from the 1st FT538 infusion

  2. Overall Response Rate

    Overall response rate is defined as number of patients who have a partial or complete response to therapy divided by the total number of patients who received treatment.

    Response criteria will be based on 2017 European LeukemiaNet (ELN) response criteria assessing the bone marrow blast percentage, presence/absence of circulating blasts, presence/absence of blasts with auer rods, presence/absence of extramedullary disease, Absolute neutrophil counts per liter pf blood and platelet counts per liter blood

    Measured: 12 months from the 1st FT538 infusion

  3. Percentage of Participants With Progression Free Survival (PFS)

    Percentage of participants experiencing progression free survival at one year follow up

    Measured: 12 months from the 1st FT538 infusion

  4. Percentage of Participants With Overall Survival (OS)

    Percentage of participants with Overall Survival (OS) at one year follow up

    Measured: 12 months from the 1st FT538 infusion

  5. Number of Participants Experiencing Adverse Events

    Number of participants experiencing adverse events with the combination of Daratumumab and FT538

    Measured: 12 months from the 1st FT538 infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jan 2021
  2. Study start3 Nov 2021
  3. Primary completion9 Jan 2024
  4. Study completion15 Oct 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
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
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04714372
Sponsor's protocol ID
2020LS114
Other IDs
MT2020-33
Status last verified
Oct 2024
First submitted
14 Jan 2021
Last updated
24 Oct 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Daratumumab/rHuPH20, FT538 and Fludarabine in people with Acute Myeloid Leukemia and Myeloid Leukemia, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Experiencing Dose Limiting Toxicity (DLT) Events (time frame: 42 days from the 1st FT538 infusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2024.

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