MGD024 for Blood Cancers

Recruiting at 8 trial locations

Overseen By Global Trial Manager

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: MacroGenics

Must not be taking: Corticosteroids, Immune suppressive drugs

Disqualifiers: CNS involvement, Anti-CD123, others

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

Compensation: Varies

Number of Visits: 1

Duration: 12 months

130 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, MGD024, for certain blood cancers that haven't responded to other treatments or have returned after treatment. The main goal is to assess the safety and tolerability of MGD024, understand its interaction with the body, and determine its potential to fight cancer. Suitable candidates have specific types of blood cancer, such as acute myeloid leukemia or Hodgkin lymphoma, and have not found success with other treatments. Participants will receive the drug in cycles and undergo close monitoring for side effects and cancer response. As a Phase 1 trial, this research aims to understand how MGD024 works in people, offering participants the chance to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that MGD024 is likely to be safe for humans?

Research has shown that MGD024 is a new treatment being tested for blood cancers. It targets cancer cells and helps the immune system attack them. Currently, this treatment is in Phase 1 trials, which primarily focus on assessing the drug's safety and tolerability.

In these early studies, patients who have not responded to other treatments receive MGD024. The main goal is to identify any side effects and assess their severity. Since this is the first time MGD024 is tested in humans, researchers have limited safety data. However, they closely monitor participants for any negative effects throughout the trial.

Due to MGD024's early testing stage, information on its safety remains limited. This phase is crucial to ensure safety before proceeding to more extensive testing. Participants in the trial are closely monitored to ensure proper management and assessment of any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about MGD024 for blood cancers because it represents a new approach in targeting cancer cells. Unlike most treatments that attack cancer directly, MGD024 is designed to engage the body’s immune system to recognize and destroy cancer cells more effectively. This treatment works by targeting specific proteins on the surface of cancer cells, potentially offering a more precise and less toxic alternative to traditional chemotherapy. Additionally, its unique mechanism of action might help overcome resistance seen with existing therapies, providing hope for better outcomes in patients with blood cancers.

What evidence suggests that MGD024 might be an effective treatment for blood cancers?

Research shows that MGD024 is an experimental treatment targeting certain blood cancers. It connects to specific markers on cancer cells and T cells, components of the immune system. This connection enhances the ability of T cells to attack cancer cells. Early lab studies have shown promising results by boosting the immune response against cancer. However, research in humans remains in the early stages, requiring further studies to confirm its effectiveness in people. Participants in this trial will receive escalating doses of MGD024 to assess safety and tolerability. ^{2 4 6 7 8}

Who Is on the Research Team?

Stephen Eck, M.D.

Principal Investigator

MacroGenics

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• MGD024

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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) 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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05362773

NCT05362773 | A Study of MGD024 in Patients With ... The study is designed to determine the safety, tolerability, pharmacokinetics (affect of the body on the drug), pharmacodynamic (affect of the drug on the body) ...

2. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/11753/488234/A-Phase-1-First-in-Human-Dose-Escalation-Study-of

A Phase 1, First-in-Human, Dose-Escalation Study of MGD024 ... MGD024 is an investigational, second-generation CD123 × CD3 DART molecule that can simultaneously bind CD123 on malignant cells and CD3 on T cells.

3. dana-farber.org dana-farber.org/clinical-trials/22-482

A Phase 1, First-in-Human, Dose Escalation Study of ... CP-MGD024-01 is a Phase 1, open-label, multi-center study of MGD024 as a single agent in participants with select blood cancers that have not responded to

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-00598

A Study of MGD024 in Patients With Relapsed or ... Participants will receive treatment with MGD024 in consecutive 28-day cycles for a study treatment period of up to 12 cycles (approximately 1 year) or until ...

5. clinicalresearch.com clinicalresearch.com/en/find-trials/Study/NCT05362773

NCT05362773 Participants will receive treatment with MGD024 in consecutive 28-day cycles for a study treatment period of up to 12 cycles (approximately 1 year) or until ...

6. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT05362773?term=mGD024&draw=2&rank=1

A Study of MGD024 in Patients With Relapsed ... CP-MGD024-01 is a Phase 1, open-label, multi-center study of MGD024 as a single agent in participants with select blood cancers that have ...

7. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/342441

A Study of MGD024 in Patients With Relapsed or Refractory ... The study is designed to determine the safety, tolerability, pharmacokinetics (affect of the body on the drug), pharmacodynamic (affect of the drug on the body) ...

8. delta.larvol.com delta.larvol.com/Products/?ProductId=8be9d489-5e39-4396-9d41-47d53cdaca3c

MGD024 / MacroGenics, Gilead A Study of MGD024 in Patients With Relapsed or Refractory Hematologic Malignancies ... P1 data • Preclinical • Breast Cancer • Genito-urinary Cancer • Head ...