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New treatment option for Acute Myeloid Leukemia
Official title DR-18 to Prevent or Treat Acute Myeloid Leukemia or Myelodysplastic Syndrome Relapse After Hematopoietic Cell Transplantation, the DR. DREAM Trial
ClinicalTrials.gov ID: NCT06492707
What this study is testing
What is Decoy-resistant interleukin-18?
Decoy-resistant interleukin-18 is an investigational medicine, given as an once-weekly injection under the skin, being studied as a potential treatment for acute myeloid leukemia.
Also referred to as Engineered IL-18 Variant ST-067, Engineered Interleukin-18 Variant ST-067.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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.
- Phase 1: an early, usually small safety study
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- ≥ 18 years of age (no upper age limit)
- 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 at any time post-HCT defined as absolute neutrophil count (ANC) ≥ 0.5 x 10\^9/L for ≥ 3 consecutive days and...
- Absent, stable or reducing immune suppression in the preceding 4 weeks without GvHD flares
- Karnofsky performance status (KPS) ≥ 80%
You likely can't join if
- Cellular immunotherapy or new targeted therapy in the 4 weeks prior to the first DR-18 injection
- History of grade 3 or 4 acute GvHD after the most recent HCT
- History of moderate or severe chronic GvHD after the most recent HCT
- Active acute or chronic GvHD or other immunologic phenomenon (e.g., immune cytopenias, cryptogenic immunologic pneumonia) in last month requiring...
- Active moderate-severe thrombotic microangiopathy (TMA) as evidenced by any of the following: \> 10 schistocytes per high-power field, or required...
- Renal insufficiency: Estimated glomerular filtration rate (eGFR) (calculated per the performing laboratory's standard formula) or measured 24 hour...
See the full eligibility criteria
Who can join
- ≥ 18 years of age (no upper age limit)
- 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 at any time 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...
- Absent, stable or reducing immune suppression in the preceding 4 weeks without GvHD flares
- Karnofsky performance status (KPS) ≥ 80%
- Agrees to use a suitable method of contraception during study treatment and for 4 months after the last dose of DR-18
- Capable of providing informed consent
- GROUP 1: Documented persistent or recurrent measurable residual AML or MDS after HCT, defined as bone marrow blasts \< 5% by morphology (unless suspected to be regenerative) and malignant bone marrow blasts \< 5% by...
- Note: MRD (\< 5% malignant blasts) must be detected with flow cytometry testing at University of Washington Medical Center (UWMC)/Fred Hutchinson Cancer Center (Fred Hutch) clinical laboratory
- GROUP 1: Absence of circulating malignant blasts detected by the complete blood count (CBC)
- GROUP 1: Absence of extramedullary disease
- GROUP 1: Post-HCT restaging never detected overt relapse or disease persistence, defined as ≥ 5% (non-regenerative) blasts by morphology or flow cytometry, or circulating malignant blasts on CBC, or extramedullary...
- GROUP 1: 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.)
- GROUP 1: No Food and Drug Administration (FDA)-approved targeted therapy for the participant's AML or MDS is available, or if such therapy is available, that class of drugs previously failed for the participant or the...
- GROUP 2: HCT is with post-transplant cyclophosphamide or other form of in vivo or ex-vivo T cell depletion
- GROUP 2: Informed consent was signed pre-HCT or latest day 28 post-HCT. (Treatment may start as early as 30 days post-HCT.)
- GROUP 2-ONLY IF AML BY WORLD HEALTH ORGANIZATION (WHO) OR INTERNATIONAL CONSENSUS CLASSIFICATION (ICC) 2022 CRITERIA: Pre-HCT bone marrow shows residual leukemia by flow cytometry (MRD or overt disease with ≥ 5% blasts)
- GROUP 2-ONLY IF AML BY WHO OR ICC 2022 CRITERIA: The participant had at least 1 course of intensive induction chemotherapy or 2 cycles of hypomethylating therapy with venetoclax or 4 cycles of hypomethylating therapy...
- GROUP 2-ONLY IF MDS BY WHO OR ICC 2022 CRITERIA: Any one of the following high-risk features was detected in the pre-HCT disease course:
- International Prognostic Scoring System-MDS (IPSS-M) score "very high" risk
- TP53 pathogenic or likely pathogenic mutation with variant allele frequency (VAF) ≥ 50%
- TP53 pathogenic or likely pathogenic mutation with VAF \< 50% and complex cytogenetics or 5q or 7q cytogenetic abnormalities
- Biallelic TP53 mutations
- The patient had at least 1 course of intensive induction chemotherapy or 2 cycles of hypomethylating therapy with venetoclax or 4 cycles of hypomethylating therapy and the pre-HCT bone marrow evaluation still shows \>...
What rules you out
- Cellular immunotherapy or new targeted therapy in the 4 weeks prior to the first DR-18 injection
- History of grade 3 or 4 acute GvHD after the most recent HCT
- History of moderate or severe chronic GvHD after the most recent HCT
- 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...
- 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...
- 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. Note: 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 participant had bloodstream infection, negative blood...
- 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...
- 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...
- 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...
- 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...
- 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%
- Pregnant or breastfeeding
The study team makes the final eligibility decision.
Where it's taking place
- Seattle, Washington, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Seattle, Washington, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.