2321GCCC: CRD3874-SI in Patients With Relapsed/Refractory AML

NCT06626633 | Suspended Phase 1 DMC FDA Drug

• 1 other identifier: 2321GCCC ; HP-00105008
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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 action of proteins called Type 1 interferons. The protein STING (for STimulator of INterferon Genes) stimulates the body to make Type 1 interferons. Type 1 interferons activate key molecules in cancer immunity to kill cancer cells. CRD3874 is a synthetic drug that activates STING, and STING stimulates the immune system to kill cancer cells. In experiments on blood from humans, CRD3874 makes blood cells produce molecules responsible for anti-cancer activity. CRD3874 was tested in mice with cancers including leukemia, head and neck cancer, lung cancer, pancreatic cancer and sarcoma. In these mice, CRD3874 made tumors shrink or disappear, and some mice developed long-lasting immunity against cancer. Also, when CRD3874 was given with other anti-cancer treatments, it increased their anti-cancer effects.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (4)

• Safety and Tolerability by multiplex cytokine profiling

  To evaluate the safety and tolerability of CRD3874-SI (a STING agonist) in patients with relapsed/refractory acute myeloid leukemia and to determine the biologically effective dose and recommended Phase 2 dose (RP2D). Exploratory studies will include measurement of additional cytokines including IFNα, IL-1α, IL-1β, IL-10, IFN-γ, TNFα, MCP-1 and GM-CSF by multiplex cytokine profiling

  2 years

• Safety and Tolerability by qPCR

  To evaluate the safety and tolerability of CRD3874-SI (a STING agonist) in patients with relapsed/refractory acute myeloid leukemia and to determine the biologically effective dose and recommended Phase 2 dose (RP2D). STING and immediate downstream targets (IRF3, IRF7, TBK1, STAT6) and NFKB pathway (GADD45a, TNFx, JUNB, NFKB2, IL7R, IKK) and IFN pathway (IFNB, ISG15, ISG20, IFI27, IFI44) targets by qPCR,

  2 years

• Safety and Tolerability by Western blot analysis

  To evaluate the safety and tolerability of CRD3874-SI (a STING agonist) in patients with relapsed/refractory acute myeloid leukemia and to determine the biologically effective dose and recommended Phase 2 dose (RP2D). STING and downstream targets including TBK1, IRF3 and IRF7, STAT6 and TNFx and phosphorylated/activated counterparts by Western blot analysis

  2 years

• Safety and Tolerability by colony formation assays

  To evaluate the safety and tolerability of CRD3874-SI (a STING agonist) in patients with relapsed/refractory acute myeloid leukemia and to determine the biologically effective dose and recommended Phase 2 dose (RP2D). Bcl-2 family proteins by Western blot analysis, apoptosis by flow cytometry and clonogenic potential by colony formation assays.

  2 years

Secondary Outcomes (4)

• Area under the plasma concentration versus time curve (AUC)

  2 years

• Peak Plasma Concentration (Cmax)

  2 years

• Trough Concentration (Ctrough)

  2 years

• Pharmacodynamic (PD) effects of CRD3874-SI

  2 years

Study Arms (1)

STING agonist CRD3874-SI in patients with relapsed/refractory acute myeloid leukemia

EXPERIMENTAL

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.

Drug: CRD3874

Interventions

CRD3874 DRUG

CRD3874-SI is a STING agonist. CRD3874 is a synthetic drug that activates STING, and STING stimulates the immune system to kill cancer cells. In experiments on blood from humans, CRD3874 makes blood cells produce molecules responsible for anti-cancer activity. CRD3874 was tested in mice with cancers including leukemia, head and neck cancer, lung cancer, pancreatic cancer and sarcoma. In these mice, CRD3874 made tumors shrink or disappear, and some mice developed long-lasting immunity against cancer.

STING agonist CRD3874-SI in patients with relapsed/refractory acute myeloid leukemia

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female age ≥ 18 years at the time of signing the ICF
• Able to understand and willing to provide written informed consent
• Willing to comply with clinical study instructions and requirements.
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 (Appendix 1).
• Pathologically confirmed diagnosis of AML by 2022 International Consensus Classification of Myeloid Neoplasms and Acute Leukemias criteria (2)
• AML may be de novo, following a prior hematologic disorder including myelodysplastic syndrome or Philadelphia chromosome-negative myeloproliferative neoplasm, and/or therapy-related
• Patients must have relapsed/refractory AML, with any prior therapies and any number of prior therapies, and have no further standard therapies available.
• Any prior therapy must have been completed ≥2 weeks prior to Day 1 of treatment on study, and all treatment-related adverse events (except alopecia) should have recovered to \<Grade 1.
• Hematologic abnormalities that are thought to be primarily related to leukemia are not considered to be toxicities and do not need to resolve to \<Grade 1.
• Myeloid growth factors must have been stopped ≥1 week (filgrastim) or ≥2 weeks (pegfilgrastim) before starting study treatment.
• Prior autologous hematopoietic stem cell transplantation is allowed.
• Prior allogeneic hematopoietic stem cell transplantation is also allowed, if patients are ≥60 days from stem cell infusion, have no evidence of graft-versus-host disease (GVHD) \>Grade 1, and are \>4 weeks off calcineurin therapy and ≥2 weeks off all immunosuppressive therapy.
• Peripheral blast count must be \<50 × 109/L. Hydroxyurea is permitted for blast count control before starting study treatment, but must be stopped ≥24 hours before starting study treatment. It may be reintroduced per physician decision if \>50 × 109/L blasts recur during treatment Cycle 1 and managed per physician decision.
• Patients with other malignancies are allowed, if other malignancies are inactive and not requiring concurrent therapy except hormonal therapy for stable breast or prostate cancer.
• Aspartate aminotransferase (AST) must be \<2.5 x Upper Limit Normal (ULN), alanine aminotransferase (ALT) \<2.5 x ULN and total serum bilirubin \<1.5 x ULN unless thought due to hemolysis or Gilbert's Syndrome.

You may not qualify if:

• Acute promyelocytic leukemia
• Blast phase of chronic myeloid leukemia
• Known active central nervous system leukemia
• Concurrent chemotherapy, radiation therapy, immunotherapy or other investigational agents
• Active, uncontrolled infection
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements in the investigator's judgment
• Malignancies other than AML requiring active therapy except hormonal therapy for stable breast or prostate cancer
• Active autoimmune disease other than vitiligo, type 1 diabetes, or controlled hypothyroidism
• Interstitial lung disease or any disease requiring supplemental oxygen, or history of pneumonitis or pulmonary fibrosis from any cause
• Known prior severe hypersensitivity to an investigational product or any component of the study drug therapy's formulations including polyethylene glycol (PEG; National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] v5.0 Grade ≥ 3)
• Prior chemotherapy or targeted small molecule therapy within 3 weeks, anticancer monoclonal antibody within four weeks or five half-lives, if shorter, or radiation therapy within 2 weeks prior to the first CRD3874-SI infusion prior to study Day 1, or not recovered (i.e., Grade ≤ 1 or at baseline) from AE due to a previously administered agent (Note: Alopecia is acceptable. If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study therapy)
• Prior organ transplantation, other than allogeneic or autologous hematopoietic stem cell transplantation.
• Currently participating in a study and receiving study therapy, or participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment or 5 half-lives, whichever is longer.
• Received a live vaccine within 30 days of the planned start of study drug. (Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines and are not allowed.)
• Evidence of clinically significant immunosuppression including the following:

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

University of Maryland, Baltimore

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: STING agonist CRD3874-SI in patients with relapsed/refractory acute myeloid leukemia

Study Record Dates

• First Submitted: August 1, 2024
• First Posted: October 4, 2024
• Study Start: August 26, 2024
• Primary Completion: August 25, 2025
• Study Completion (Estimated): January 31, 2028
• Last Updated: March 12, 2026

Record last verified: 2026-03

Locations

US (1)