Trial Title:
DR-18 for the Treatment of Relapsed or Persistent Acute Myeloid Leukemia or Myelodysplastic Syndrome After Hematopoietic Cell Transplantation, the DR. DREAM Trial
NCT ID:
NCT06492707
Condition:
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Recurrent Acute Myeloid Leukemia
Recurrent Myelodysplastic Syndrome
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Myelodysplastic Syndromes
Syndrome
Recurrence
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Decoy-resistant interleukin-18
Description:
Given SC
Arm group label:
Treatment (DR-18)
Other name:
Engineered IL-18 Variant ST-067
Other name:
Engineered Interleukin-18 Variant ST-067
Other name:
ST 067
Other name:
ST-067
Other name:
ST067
Other name:
VEVOCTADEKIN
Other name:
DR-18
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (DR-18)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Marrow Aspiration
Description:
Undergo bone marrow aspiration
Arm group label:
Treatment (DR-18)
Summary:
This phase I trial tests the safety, side effects and best dose of decoy-resistant
interleukin-18 (DR-18) and how well it works in treating patients with acute myeloid
leukemia (AML) or myelodysplastic syndrome (MDS) that has come back after a period of
improvement (relapsed) or that remains despite treatment (persistent) after hematopoietic
cell transplantation (HCT). HCT is the only curative therapy for most forms of AML and
MDS. However, relapse occurs in a third of patients and is the most common cause of death
after HCT. DR-18, a variant of the human cytokine interleukin-18, binds to IL-18 binding
probein (IL-18BP) and overcomes the inhibitory effect of the IL-18BP on IL-18, which may
boost the body's immune system and may interfere with the ability of tumor cells to grow
and spread. Giving DR-18 may be safe, tolerable and/or effective in treating patient with
relapsed or persistent AML or MDS after HCT.
Detailed description:
OUTLINE: This is a dose-escalation study.
INDUCTION: Patients receive DR-18 subcutaneously (SC) once weekly on approximately days
0, 7, 14, and 21.
MAINTENANCE: Two weeks after induction treatment, patients without grade 3-4 acute GVHD,
grade 2 acute GVHD requiring ongoing systemic immunosuppression, or moderate/severe
chronic GVHD may receive DR-18 SC once weekly on approximately days 35, 42, 49 and 56.
Additionally, patients undergo blood and bone marrow sample collection throughout the
study.
After completion of study treatment, patients are followed weekly for 4 weeks, monthly
through 6 months and at 12 months.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- ≥ 18 years of age (no upper age limit)
- Documented persistent or recurrent AML or MDS after HCT (including measurable
residual disease [MRD] or overt leukemia). Nota bene (NB): MRD must be detected with
flow cytometry testing at University of Washington Medical Center (UWMC)/Fred
Hutchinson Cancer Center (Fred Hutch) clinical laboratory
- No Food and Drug Administration (FDA)-approved targeted therapy for the subject's
AML or MDS is available, or if such therapy is available, that class of drugs
previously failed for the subject or the subject was intolerant of the therapy
- No history of grade 3 or 4 acute GvHD after the most recent HCT
- No history of moderate or severe chronic GvHD after the most recent HCT
- No active acute or chronic GvHD or other immunologic phenomenon (e.g., immune
cytopenias, cryptogenic immunologic pneumonia) in last month requiring systemic
therapy (Hydrocortisone or prednisone for adrenal insufficiency at ≤ 10 mg/day
prednisone-equivalent is permitted.)
- Stable or reducing immune suppression in the preceding 4 weeks without GvHD flares
- The most recent HCT was from a 10/10 human leukocyte antigen (HLA)-matched related
or unrelated donor (assessed at HLA-A, B, C, DR, DQ)
- Evidence of blood count recovery post-HCT defined as absolute neutrophil count (ANC)
≥ 0.5 x 10^9/L for ≥ 3 consecutive days and platelets ≥ 30 x 10^9/L (independent of
granulocyte colony-stimulating factor [G-CSF] or platelet transfusions for 5 days)
- No cellular immunotherapy or new targeted therapy in the 4 weeks prior to enrollment
- Karnofsky performance status (KPS) ≥ 80%
- Not pregnant/breastfeeding
- Agrees to use a suitable method of contraception for 4 months after the last dose of
DR-18
- Capable of providing informed consent
- At least 60 days have elapsed since the HCT donor cell infusion (HCT day 0). (There
is no upper limit to the time elapsed since HCT.)
Exclusion Criteria:
- Active moderate-severe thrombotic microangiopathy (TMA) as evidenced by any of the
following: > 10 schistocytes per high-power field, or required anti-C5 or other
anti-complement therapy for TMA in the prior 4 weeks, any of the following
manifestations if attributed to TMA in the prior 4 weeks: hypertension, worsening or
new renal insufficiency, ≥ 2+ proteinuria, hematochezia, seizure, transient or
ongoing neurologic deficits
- Renal insufficiency: Estimated glomerular filtration rate (eGFR) (calculated per the
performing laboratory's standard formula) or measured 24 hour (hr.) creatinine
clearance < 30 mL/min
- Hemodialysis in the prior 4 weeks
- Major cardiac event requiring evaluation in the emergency room (ER) or
hospitalization in the past 4 weeks
- New York Heart Association (NYHA) class II or higher congestive heart failure (CHF)
in the past 4 weeks
- Uncontrolled cardiac arrhythmias, including atrial fibrillation
- Left ventricular ejection fraction (LVEF) < 35%. LVEF may be established with
echocardiogram or MUGA scan, and left ejection fraction must be ≥ 35%
- Liver dysfunction: aspartate aminotransferase (AST) or alanine aminotransferase
(ALT) > 5 x upper limit of normal (ULN) or bilirubin > 3 x ULN
- Active uncontrolled infection. NB: Examples of controlled infections:
- Bacterial infection may be still requiring antibiotics at the time of
enrollment, but clinical signs and symptoms of the infection should be
improving. If the subject had bloodstream infection, negative blood cultures
off antibiotics must be documented prior to initiating DR-18 treatment. For
urinary tract infection, a repeat urine culture must be sterile prior to
initiating DR-18. Radiographic improvement of bacterial pneumonia may lag
behind clinical improvement so is not mandatory prior to DR-18 initiation
- Fungal infection may be still requiring antifungal medication at the time of
enrollment, but evidence of clinical response to antifungal medication (such as
regression of lesions on chest CT) must be available at the time of enrollment
- Asymptomatic shedding of respiratory viruses after cessation of antiviral
therapy, or if not specifically treated with antiviral therapy, is permitted
- Cytomegalovirus (CMV) viremia or organ infection meeting institutional criteria
for CMV treatment with antiviral therapy such as ganciclovir, valganciclovir or
foscarnet must be on maintenance phase of treatment or must have completed
treatment and must not be in the induction treatment phase at the time of
enrollment. Low-level CMV viremia not meeting institutional criteria for
antiviral therapy is permitted, including low-level viremia in patients
receiving CMV prophylaxis with letermovir
- Any of the following: Pulmonary dysfunction requiring supplemental oxygen, even
intermittently, in the past 2 weeks; corrected diffusion capacity of the lung for
carbon monoxide (DLCO) or forced expiratory volume in 1 second (FEV1) < 60%
predicted; bronchiolitis obliterans syndrome; prior diagnosis of idiopathic
pulmonary fibrosis; prior diagnosis of drug-induced pneumonitis; cryptogenic
organizing pneumonia under active treatment
- Seizure in the past 4 weeks or significant underlying neurologic disease: Study
participants must not have significant active underlying neurologic disease, such as
Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy,
prior symptomatic ischemic or hemorrhagic stroke, or transient ischemic attack,
unless approved by principal investigator (PI). Peripheral neuropathy related to
diabetes or prior chemotherapy is acceptable
- Other medical, social, or psychiatric factor that interferes with medical
appropriateness and/or ability to comply with study, as determined by the PI
- Known allergic reactions to any of the components of study treatments
- Concurrent use of other investigational anti-cancer agents
- Peripheral blood T cell chimerism < 40%
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Fred Hutch/University of Washington Cancer Consortium
Address:
City:
Seattle
Zip:
98109
Country:
United States
Status:
Recruiting
Contact:
Last name:
Elizabeth Krakow
Phone:
206-667-3410
Email:
efkrakow@fredhutch.org
Investigator:
Last name:
Elizabeth Krakow
Email:
Principal Investigator
Start date:
September 23, 2024
Completion date:
May 1, 2027
Lead sponsor:
Agency:
Fred Hutchinson Cancer Center
Agency class:
Other
Collaborator:
Agency:
Simcha Therapeutics
Agency class:
Other
Source:
Fred Hutchinson Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06492707
