CRD3874 for AML

Overseen By Sunita Philip

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Maryland, Baltimore

Must not be taking: Immunosuppressants, Chemotherapy

Disqualifiers: Acute promyelocytic leukemia, CNS leukemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests CRD3874, a new drug designed to help the immune system combat acute myeloid leukemia (AML), a type of blood cancer. CRD3874 activates a protein called STING, enhancing the body's natural defenses to target and kill cancer cells. The trial seeks participants with AML that has returned or not responded to previous treatments. This offers an opportunity for those who have tried other therapies without success to potentially benefit from a novel approach. Participants should be prepared to follow the study's requirements and have no other standard treatment options available. As a Phase 1 trial, this research focuses on understanding how CRD3874 works in people, offering participants the chance to be among the first to receive this innovative treatment.

Will I have to stop taking my current medications?

The trial requires that any prior therapy must be completed at least 2 weeks before starting the study treatment, and certain medications like myeloid growth factors and hydroxyurea must be stopped 1-2 weeks before starting. If you are on systemic immunosuppressive therapy or certain other treatments, you may need to stop them before joining the trial.

Is there any evidence suggesting that CRD3874 is likely to be safe for humans?

Research has shown that CRD3874, a man-made drug, has promising safety results from early studies. In tests on mice, it helped shrink or eliminate tumors and was generally well-tolerated. Although limited information exists from human studies, tests on human blood suggest that CRD3874 can activate the immune system to fight cancer. This Phase 1 trial focuses on determining the drug's safety for people, indicating that it remains in the early stages of testing. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for acute myeloid leukemia (AML), which typically involve chemotherapy or targeted therapy drugs, CRD3874 is a synthetic small molecule that acts as a STING agonist. This means it stimulates the immune system's innate response by activating the STING pathway, potentially leading to a more robust attack on cancer cells. Researchers are excited about CRD3874 because it offers a novel approach by harnessing the body's own immune system to fight the leukemia, which could provide new hope for patients with relapsed or refractory AML, especially those who have not responded well to conventional therapies.

What evidence suggests that CRD3874 might be an effective treatment for AML?

Research has shown that CRD3874, the investigational treatment in this trial, activates a protein called STING, which aids the immune system in fighting cancer. In lab tests, CRD3874 prompted human blood cells to produce substances that help destroy cancer cells. In animal studies, CRD3874 caused tumors in mice to shrink or disappear in cases of leukemia, lung, and other cancers. Some mice even developed long-lasting protection against cancer. When combined with other cancer treatments, CRD3874 enhanced their effectiveness, suggesting it could be a powerful partner in cancer therapy. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for patients with relapsed or refractory Acute Myeloid Leukemia (AML) who have tried other treatments without success. Participants must meet specific health criteria to join, but these details are not provided here.

Inclusion Criteria

Able to understand and willing to provide written informed consent

Willing to comply with clinical study instructions and requirements

Peripheral blast count <50 × 10^9/L

Exclusion Criteria

Severe hypersensitivity to study drug components

Current participation in other studies or use of investigational agents

Evidence of clinically significant immunosuppression

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CRD3874-SI via IV infusion once weekly for 28-day cycles

6 months

Weekly visits for infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• CRD3874

Trial Overview The study tests CRD3874, a synthetic drug designed to activate the STING protein in the body's immune system, potentially helping it produce molecules that fight cancer cells and improve responses to other anti-cancer treatments.

How Is the Trial Designed?

Group I: STING agonist CRD3874-SI in patients with relapsed/refractory acute myeloid leukemia Experimental Treatment 1 Intervention

Drug Product: CRD3874 solution for injection (CRD3874-SI) Type of drug: Synthetic small molecule Formulation: Sterile solution of CRD3874 for injection Route of Administration: IV infusion over one hour Strength: 6 mg/mL Schedule: Cycle: once weekly infusion x 4 (Days 1, 8, 15 and 22) over 28-day for Cycles 1 and 2. For Cycle 3 and onward, weekly infusion x 3 (Days 1, 8 and 15), until they develop unacceptable toxicities or disease progression, or do not achieve at least a morphologic leukemia-free state response after 6 cycles.

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Published Research Related to This Trial

In a study of 34 acute myeloid leukemia (AML) cases, CD123 was found to be significantly overexpressed in leukemic stem cells (LSCs), specifically in the CD34+/CD38-/CD123+ subpopulation, indicating its potential as a therapeutic target.

FLT3/ITD mutations, which are important in leukemia development, were exclusively detected in the CD34+/CD38-/CD123+ LSCs, suggesting that targeting CD123 with antibodies and combining it with FLT3 inhibitors could enhance treatment effectiveness against these resistant cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunoprofiling of leukemic stem cells CD34+/CD38-/CD123+ delineate FLT3/ITD-positive clones. Al-Mawali, A., Gillis, D., Lewis, I.[2018]

In a study of 142 acute myeloid leukemia (AML) patients, high CXCR4 expression was found to correlate with increased leukemic burden and other clinical features such as high platelet count and organ enlargement.

CXCR4 expression serves as an independent prognostic factor in AML, suggesting that targeting CXCR4 could be a promising therapeutic strategy for improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CXCR4 expression accounts for clinical phenotype and outcome in acute myeloid leukemia. Mannelli, F., Cutini, I., Gianfaldoni, G., et al.[2021]

In a study of 304 AML patients, those with CD7 expression showed higher levels of HLA-DR and CD33, indicating a distinct immunophenotype that suggests these cells originate from earlier stages of blood cell development.

Patients with CD4 expression exhibited higher levels of CD15, CD64, and CD33, indicating a more mature hematological development, and the study suggests that the expression levels of CD4 and CD7 can help in quantitatively detecting minimal residual disease (MRD) in AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Features of Immunophenotypes and Characteristics of Molecular Biology and Cellular Genetics of AML Patients with CD4 and CD7 Expression]. Liu, TQ., Huang, S., Yao, B., et al.[2018]

In a study of 105 acute myeloid leukaemia (AML) cases, CDw131 expression levels helped identify two subgroups: one with low expression (75 cases) and another with high expression (30 cases), which correlated with distinct biological characteristics.

AMLs with high CDw131 expression were associated with increased cell cycling, specific receptor expressions (like CD11b and CD14), and mutations such as FLT3 internal tandem duplication, suggesting potential targets for new therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin (IL)-3/granulocyte macrophage-colony stimulating factor/IL-5 receptor alpha and beta chains are preferentially expressed in acute myeloid leukaemias with mutated FMS-related tyrosine kinase 3 receptor. Riccioni, R., Diverio, D., Riti, V., et al.[2022]

LINC00324 is down-regulated in the peripheral blood leukocytes of acute myeloid leukemia (AML) patients and its expression correlates significantly with important immunophenotypes like CD33, as well as red blood cell and platelet counts.

The study suggests that LINC00324 may play a role in regulating immune cell differentiation and function, indicating its potential as a target for new drug development in AML treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Correlation analysis between LINC00324 and immunophenotype in peripheral blood leukocytes in patients with acute myeloid leukemia]. Liu, Y., Zhang, Y., Xie, J., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06626633

NCT06626633 | 2321GCCC: CRD3874-SI in Patients With ... To evaluate the safety and tolerability of CRD3874-SI (a STING agonist) in patients with relapsed/refractory acute myeloid leukemia and to determine the ...

2. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT191/761418/Abstract-CT191-Intravenous-infusion-of-the

Abstract CT191: Intravenous infusion of the allosteric small ... Intravenous infusion of the allosteric small molecule STING agonist CRD3874-SI in patients with relapsed or refractory acute myeloid leukemia: A phase I trial

3. researchgate.net researchgate.net/publication/391170334_Abstract_CT191_Intravenous_infusion_of_the_allosteric_small_molecule_STING_agonist_CRD3874-SI_in_patients_with_relapsed_or_refractory_acute_myeloid_leukemia_A_phase_I_trial

Abstract CT191: Intravenous infusion of the allosteric small ... Abstract CT191: Intravenous infusion of the allosteric small molecule STING agonist CRD3874-SI in patients with relapsed or refractory acute ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12030840/

Progress Update on STING Agonists as Vaccine Adjuvants In this review, we present the latest research on natural and synthetic STING agonists that have been effectively used in vaccine development.

5. delta.larvol.com delta.larvol.com/Products/?ProductId=52359f79-f192-4b86-991c-207305b93f2d

CRD3874 / Curadev Intravenous infusion of the allosteric small molecule STING agonist CRD3874-SI in patients with relapsed or refractory acute myeloid leukemia: A phase I trial ...

6. adisinsight.springer.com adisinsight.springer.com/trials/700377104

Phase 1 Clinical Trial of the STING Agonist CRD3874-SI in ... This clinical research study is being done to answer questions about how to treat cancer. To clear cancer cells from the body, the immune system needs the.

7. ctsearchsupport.org ctsearchsupport.org/clinical-trials/2321gccc-crd3874-si-in-patients-with-relapsed-refractory-aml

Trial Summary | NMDP℠ CTSS The highest dose of CRD3874 that's safe to give; If CRD3874 is safe and works well to treat AML that has relapsed or is refractory. You may be ...

8. asco.org asco.org/abstracts-presentations/ABSTRACT456182

Phase I trial of CRD3874-SI, a systemically administered ... It has demonstrated promising pre-clinical anti-cancer activity in several tumor mouse models. CRD3874-SI demonstrated high levels of systemic safety in ...