MGD024 for Blood Cancers

Recruiting at8 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: MacroGenics

Must not be taking: Corticosteroids, Immune suppressive drugs

Disqualifiers: CNS involvement, Anti-CD123, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called MGD024 in patients with certain blood cancers that haven't responded to other treatments. Researchers want to see if MGD024 is safe, how it works in the body, and if it helps fight cancer. Patients will receive the drug periodically, and their response will be monitored regularly.

Will I have to stop taking my current medications?

The trial requires that you stop taking any systemic anti-cancer therapy, investigational therapy, corticosteroids, or other immune suppressive drugs at least 14 days before starting the study treatment.

How is the drug MGD024 unique for treating blood cancers?

MGD024, also known as IL-24, is unique because it enhances the immune system's ability to recognize and attack cancer cells, increases the sensitivity of cancer cells to chemotherapy, and induces cancer cell death by affecting specific genes and proteins involved in cell survival and resistance. ^{1 2 3 4 5}

Research Team

Ashley Ward, M.D.

Principal Investigator

MacroGenics

Eligibility Criteria

This trial is for adults over 18 with certain blood cancers like AML, MDS, Hodgkin's lymphoma, and others who've had no luck with standard treatments or have seen their cancer return. They must be able to consent, follow study rules, have a life expectancy of at least 12 weeks, decent lab results and heart function. Participants need to use effective birth control and can't join if they've had CNS disease involvement or recent other treatments.

Inclusion Criteria

My cancer cells show CD123 presence.

I have been diagnosed with a specific blood cancer type.

I am 18 or older, can give consent, and will follow the study rules.

Exclusion Criteria

History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient

I have not been treated with anti-CD123 drugs, except if I have BPDCN and received tagraxofusp.

I haven't taken any cancer drugs, steroids, or immune suppressants in the last 14 days.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive treatment with MGD024 in consecutive 28-day cycles for up to 12 cycles (approximately 1 year) or until treatment or study discontinuation criteria are met

12 months

Response assessments after Cycle 1 and every even numbered cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• MGD024 (Monoclonal Antibodies)

Trial Overview MGD024 is being tested in patients with specific relapsed or treatment-resistant blood cancers. The study aims to evaluate the drug's safety, how it affects and is processed by the body, whether it triggers immune responses (like antibodies), and its initial effectiveness against cancer over up to one year of treatment cycles.

Participant Groups

Group I: Dose Escalation Experimental Treatment 1 Intervention

Escalating doses of MGD024 will be assigned based on safety and tolerability of the previous dose level.

Who Is Running the Clinical Trial?

MacroGenics

Lead Sponsor

Trials

51

Recruited

5,400+

Findings from Research

Interleukin-24 (IL-24) enhances the immunogenicity of myelogenous leukemia cells, making them more recognizable and sensitive to immune attacks, which could improve treatment outcomes.

In vivo studies in athymic nude mice showed that IL-24 not only slows down tumor growth but also reduces the expression of proteins related to angiogenesis and metastasis, highlighting its potential as a therapeutic agent for leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity moderation effect of interleukin-24 on myelogenous leukemia cells. Yu, X., Miao, J., Xia, W., et al.[2019]

The study found that mda-7/IL-24 significantly inhibits cell growth and colony formation in hematopoietic malignancies, specifically in leukemia (K562) and lymphoma (Namalwa) cell lines, indicating its potential as an effective treatment.

The mechanism of action involves G(0)/G(1) cell-cycle arrest, linked to changes in key regulatory proteins, suggesting that mda-7/IL-24 could be a promising therapeutic agent for chronic myelogenous leukemia and lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

mda-7/IL-24 inhibits the proliferation of hematopoietic malignancies in vitro and in vivo. Dong, CY., Zhang, F., Duan, YJ., et al.[2012]

Overexpression of Mda-7/IL-24 in human B cell lymphoma cells significantly increased their sensitivity to chemotherapy agents like cis-diamminedichloroplatinum (CDDP), epirubicin, and vinblastine, as evidenced by lower IC50 values and higher rates of cell growth inhibition and apoptosis.

Mda-7/IL-24 enhances chemotherapy sensitivity by downregulating multidrug resistance genes and suppressing the GTP-RhoA-ERK signaling pathway, suggesting a potential strategy to overcome drug resistance in B cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mda-7/IL-24 enhances sensitivity of B cell lymphoma to chemotherapy drugs. Ma, M., Zhao, L., Sun, G., et al.[2018]

Interleukin-24 (IL-24) shows significant potential in suppressing growth and inducing apoptosis in human myeloid leukemia cells, as demonstrated by the use of an RGD-engineered recombinant adenoviral vector (Ad.RGD-IL-24) that effectively transfers the IL-24 gene into these cells.

In vivo studies in athymic nude mice revealed that IL-24 not only induces apoptosis through specific molecular pathways but also retards the growth of transplanted leukemia tumors, highlighting its promising role in immuno-gene therapy for myeloid leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor effect and underlying mechanism of RGD-modified adenovirus mediated IL-24 expression on myeloid leukemia cells. Yu, X., Xia, W., Li, S., et al.[2021]

Interleukin-24 (IL-24) effectively induces apoptosis in bone marrow mononuclear cells (BMMNC) from children with acute leukemia, as demonstrated in a study involving 40 children (20 with acute lymphocytic leukemia and 20 with acute myeloid leukemia) who had not received therapy.

The mechanism of IL-24's action involves decreasing the expression of the anti-apoptotic protein bcl-2 and increasing the expression of the pro-apoptotic protein caspase-3, suggesting a potential therapeutic role for IL-24 in treating acute leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Apoptosis inducing effect of interleukin 24 on bone marrow mononuclear cells from children with acute leukemias in vitro]. Cheng, HR., Wen, FQ., Li, B., et al.[2016]

References

1. England pubmed.ncbi.nlm.nih.gov

Immunogenicity moderation effect of interleukin-24 on myelogenous leukemia cells. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

mda-7/IL-24 inhibits the proliferation of hematopoietic malignancies in vitro and in vivo. [2012]

3. Greece pubmed.ncbi.nlm.nih.gov

Mda-7/IL-24 enhances sensitivity of B cell lymphoma to chemotherapy drugs. [2018]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Antitumor effect and underlying mechanism of RGD-modified adenovirus mediated IL-24 expression on myeloid leukemia cells. [2021]

5. China pubmed.ncbi.nlm.nih.gov

[Apoptosis inducing effect of interleukin 24 on bone marrow mononuclear cells from children with acute leukemias in vitro]. [2016]