FT538 in Combination With Daratumumab in AML Acute Myeloid Leukemia

• Register: ClinicalTrials.gov
• Last refreshed on: 4 November 2024
• Main ID: NCT04714372
• Date of registration: 14/01/2021
• Prospective Registration: Yes
• Primary sponsor: Masonic Cancer Center, University of Minnesota
• Public title: FT538 in Combination With Daratumumab in AML Acute Myeloid Leukemia
• Scientific title: Study of FT538 in Combination With Daratumumab in Acute Myeloid Leukemia
• Date of first enrolment: November 3, 2021
• Target sample size: 9
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT04714372
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Joseph Maakaron, MD
• Affiliation: Masonic Cancer Center, University of Minnesota

Key inclusion & exclusion criteria

Disease specific Inclusion Criteria:

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

Inclusion Criteria:

- 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

- 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.

Exclusion Criteria:

- 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.


Age minimum: 12 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Monocytic Leukemia

Myeloid Leukemia

Acute Myeloid Leukemia

Intervention(s)

Drug: Cyclophosphamide

Drug: Daratumumab/rHuPH20

Drug: Fludarabine

Drug: FT538

Primary Outcome(s)

Number of Participants Experiencing Dose Limiting Toxicity (DLT) Events [Time Frame: 42 days from the 1st FT538 infusion]

Secondary Outcome(s)

Percentage of Participants With Progression Free Survival (PFS) [Time Frame: 12 months from the 1st FT538 infusion]

Number of Participants Experiencing Adverse Events [Time Frame: 12 months from the 1st FT538 infusion]

Overall Response Rate [Time Frame: 12 months from the 1st FT538 infusion]

Percentage of Participants With Overall Survival (OS) [Time Frame: 12 months from the 1st FT538 infusion]

Number of Participants Achieving Complete Remission (CR + CRi) [Time Frame: 28 days from the 1st FT538 infusion]

Secondary ID(s)

2020LS114

MT2020-33

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 24/10/2024
• URL: https://clinicaltrials.gov/ct2/show/results/NCT04714372