MGD024 for Blood Cancers

Recruiting in Palo Alto (17 mi)

+8 other 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.

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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

Participant Groups

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.

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

washington University School of Medicine Saint Louis, MO

South Texas Accelerated Research Therapeutics, LLC - Midwest Grand Rapids, MI

Colorado Blood Cancer Network Denver, CO

University of Maryland, Greenbaum Comprehensive Cancer Center Baltimore, MD

More Trial Locations

Who Is Running the Clinical Trial?

MacroGenics Lead Sponsor

References

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

Immunogenicity moderation effect of interleukin-24 on myelogenous leukemia cells. [2019] Previous studies have shown that interleukin-24 (IL-24) has tumor-suppressing activity by multiple pathways. However, the immunogenicity moderation effect of IL-24 on malignant cells has not been explored extensively. In this study, we investigated the role of IL-24 in immunogenicity modulation of the myelogenous leukemia cells. Data show that myelogenous leukemia cells express low levels of immunogenicity molecules. Treatment with IL-24 could enhance leukemia cell immunogenicity, predominantly regulate leukemia cells to produce immune-associated cytokines, and improve the cytotoxic sensitivity of these cells to immune effector cells. IL-24 expression could retard transplanted leukemia cell tumor growth in vivo in athymic nude mice. Moreover, IL-24 had marked effects on downregulating the expression of angiogenesis-related proteins vascular endothelial growth factor, cluster of differentiation (CD) 31, CD34, collagen IV and metastasis-related factors CD147, membrane type-1 matrix metalloproteinase (MMP), and MMP-2 and MMP-9 in transplanted tumors. These findings indicated novel functions of this antitumor gene and characterized IL-24 as a promising agent for further clinical trial for hematologic malignancy immunotherapy.

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

mda-7/IL-24 inhibits the proliferation of hematopoietic malignancies in vitro and in vivo. [2012] Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) has been consistently shown to exert growth inhibitory effects on various tumor types. However, the majority of these reports were limited to solid tumors. The purpose of this study was to investigate the antitumor activity of mda-7/IL-24 and the underlying mechanism in hematopoietic malignancies.

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

Mda-7/IL-24 enhances sensitivity of B cell lymphoma to chemotherapy drugs. [2018] Interleukin-24 (IL-24) is a cytokine encoded by a tumor suppressor gene of the IL-10 family, also known as the melanoma differentiation associated gene-7 (Mda-7) and first discovered in human melanoma cells. Mda-7/IL-24 has been shown to inhibit the proliferation of various human tumor cell lines, but its effect on the sensitivity of B cell lymphoma to chemotherapy agents is not yet clear. The present study investigated the effects of Mda-7/IL-24 overexpression on the sensitivity of human B cell lymphoma cells to chemotherapy, as well as its mechanism of action. The sensitivity of stable Mda-7/IL-24 overexpressing Raji and Daudi cells to cis-diamminedichloroplatinum (CDDP), epirubicin and vinblastine (VCR) were assessed by the MTS method, and the IC50 value calculated. Cell apoptosis and the intracellular accumulation of Rhodamine-123 were assayed by flow cytometry. The expression of multidrug resistance gene 1 (MDR1), B-cell-specific Moloney murine leukemia virus insertion site 1 (BMI1), topoisomerase II (Topo II) and multidrug resistance-related protein 1 (MRP1) mRNA and protein were analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting, respectively. In addition, western blot analysis was also used to investigate the effect of Mda-7/IL-24 on activity of GTP-RhoA-ERK signaling pathway in Raji and Daudi cells. Growth inhibition and apoptosis rates of Mda-7/IL-24 overexpressing Raji and Daudi cells were higher than those of non-transfected cells and cells transfected with vector alone when treated with CDDP, epirubicin and VCR. The IC50 values of CDDP, epirubicin and VCR were lower for Mda-7/IL-24-overexpressing Raji and Daudi cells than for non-transfected cells and cells transfected with empty vector. Intracellular accumulation of Rhodamine-123 and the expression of Topo II were higher, while the levels of MDR1, BMI and MRP1 mRNA and protein were lower, in Mda-7/IL-24 overexpressing Raji and Daudi cells. Furthermore, the activities of GTP-RhoA-ERK signaling pathway in Raji and Daudi cells were suppressed. These results indicated that Mda-7/IL-24 enhanced the sensitivity of B lymphoma cells to chemotherapy agents by altering the expression of multidrug-resistance genes via downregulating GTP-RhoA-ERK signaling pathway, suggesting that treatment of B cell lymphomas with Mda-7/IL-24 could avoid MDR.

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] Interleukin-24 (IL-24), a member of the IL-10 cytokine gene family, causes growth suppression and apoptosis in various solid tumor cells. However, the effects of IL-24 on hematopoietic malignant cells have not been extensively explored. In this report, we constructed an RGD-engineered recombinant adenoviral vector, Ad.RGD-IL-24, and assessed its effects on human myeloid leukemia cells. Ad vector mediates gene transfer into leukemia cells with high efficiency. Ectopic over-expression of IL-24 has significant growth inhibition and differentiation inducement effects on these cells. Treatment with Ad.RGD-IL-24 could potentially induce leukemia cells' cell-cycle arrest. In addition, IL-24 expression could significantly induce apoptosis of the THP-1 cells. Ad.RGD-IL-24 had a potent effect on the up-regulation of the expression of GRP78/Bip, GADD34 and Bax, down-regulation of the expression of Bcl-2 and Mcl-1, and induced the activation of Caspase-3, which may be responsible for its apoptosis-inducing effect on THP-1 cells. Furthermore, IL-24 expression could retard transplanted leukemia cell tumor growth in vivo in athymic nude mice. These findings showed the marked antitumor activity of IL-24 and provided potential perspectives in designing therapeutic or vaccine strategies in immuno-gene therapy of myeloid leukemia.

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] The aim of this study was to investigate the in vitro effect of interleukin-24 (IL-24) on apoptosis of bone marrow mononuclear cells (BMMNC) in children with acute leukemia. Every group of acute lymphocytic leukemia (ALL) and acute myeloid leukemia (ANLL) had 20 children who did not receive any therapy. The bone marrow was taken from patients and controls, the MNC were isolated from bone marrow, DNA was detected by glucose electrophoresis. Apoptosis of BMMNC was assayed by flow cytometry with propidium iodine staining. RT-PCR was used to detect the expression level of bcl-2, caspase-3 mRNA, and to analyze the effect of IL-24 on them. The results showed that the IL-24 induced apoptosis of BMMNC in children with acute leukemia. After acute leukemia BMMNC were exposed to IL-24 for 48 hours, DNA ladder fragment appeared, and the apoptotic rate of the group treated with IL-24 of 50 ng/ml was obviously higher than that of the control group (0 ng/ml). IL-24 decreased the bcl-2 mRNA expression level, enhanced caspase-3 mRNA expression level of BMMNC from AL patients. It is concluded that the IL-24 can induce apoptosis of AL BMMNC in vitro, which may be due to decreasing of bcl-2 mRNA level and enhancing of caspase-3 mRNA level.