MGD024 for Blood Cancers
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: MacroGenics
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.
What data supports the idea that MGD024 for Blood Cancers is an effective treatment?The available research does not provide specific data on the effectiveness of MGD024 for Blood Cancers. Instead, it discusses other treatments and factors related to blood cancers, such as myelodysplastic syndromes (MDS) and myeloid leukemia. For example, the research highlights the importance of genetic mutations in predicting outcomes for MDS and the role of minimal residual disease in myeloid leukemia of Down syndrome. However, there is no direct comparison or data on MGD024's effectiveness in these studies.79101213
Is the drug MGD024 a promising treatment for blood cancers?Yes, MGD024, also known as IL-24, shows promise as a treatment for blood cancers. It can slow down the growth of cancer cells, make them more sensitive to chemotherapy, and help the immune system fight the cancer. It also helps in reducing the spread of cancer by affecting certain proteins related to cancer growth and spread.13568
Do I need to stop my current medications to join the trial?Yes, you must stop systemic anti-cancer therapy, investigational therapy, corticosteroids, or other immune suppressive drugs at least 14 days before the first dose.
What safety data exists for MGD024 in blood cancer treatment?The provided research does not contain specific safety data for MGD024 in the treatment of blood cancers. The articles focus on various therapies and advancements in the treatment of myelodysplastic syndromes (MDS), but MGD024 is not mentioned. Therefore, no safety data for MGD024 can be extracted from these sources.24111415
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
I have been diagnosed with a specific blood cancer type.
My condition did not improve after at least one treatment and there are no cure options left.
My cancer cells show CD123 presence.
I can take care of myself and am up and about more than half of my waking hours.
Exclusion Criteria
My cancer has spread to my brain or spinal cord.
Treatment Details
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.
1Treatment groups
Experimental Treatment
Group I: Dose EscalationExperimental Treatment1 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 nearbySelect from list below to view details:
washington University School of MedicineSaint Louis, MO
South Texas Accelerated Research Therapeutics, LLC - MidwestGrand Rapids, MI
Colorado Blood Cancer NetworkDenver, CO
University of Maryland, Greenbaum Comprehensive Cancer CenterBaltimore, MD
More Trial Locations
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Who is running the clinical trial?
MacroGenicsLead Sponsor
References
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.
Treatment of MDS: something old, something new, something borrowed... [2018]As opposed to the treatment landscape for myelodysplastic syndromes (MDS) two decades ago, potential therapies now abound for the treatment of lower-risk and higher-risk populations. In lower-risk patients, decision tools can be used to determine the likelihood of response to erythropoiesis stimulating agents (ESAs), which have demonstrated survival advantages in retrospective studies in patients with MDS, and whether these patients should be treated initially with ESAs or non-growth factor ("active") therapies. Lenalidomide has shown good activity in transfusion-dependent patients with the del(5q) cytogenetic abnormality and modest activity in other lower-risk patients. In higher-risk patients, the DNA methyltransferase inhibitors produce complete and partial responses in 20% to 30% of patients, and for the first time, the MDS drug azacitidine has demonstrated a survival advantage when compared with conventional therapies. Newer therapies stimulate platelet production and target novel pathways, while a panoply of combination studies are underway or recently completed and that likely represent the next frontier in MDS therapy.
[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.
Incidence and Burden of the Myelodysplastic Syndromes. [2018]Since 2001, cases of myelodysplastic syndromes (MDSs) have been tracked by cancer registries. Examining registry data in the USA, the reported age-adjusted incidence of MDS per 100,000 was 3.3 per year for 2001-2003 and 4.9 per year for 2007-2011, with increases likely a result of growing awareness of reporting requirements. However, active case-finding methods repeatedly demonstrate that population-based registries have underestimated the incidence of MDS due to underreporting and underdiagnosis. Using keyword search strategies of electronic pathology reports or other novel case capture methods, the true incidence of MDS has been estimated between 5.3 and 13.1 per 100,000. Using Medicare billing claims data, the incidence of MDS per 100,000 in patients aged ≥65 years has been estimated between 75 and 162. MDS prevalence is estimated to be 60,000 and -170,000 in the USA and projected to grow. Epidemiologic data can help estimate the burden of MDS and expose unmet clinical needs. For example, patients with MDS receiving transfusions had significantly higher reported health care costs versus those that did not (3-year mean of $88,824 vs $29,519). Epidemiologic data also revealed that most MDS patients receiving transfusions do not receive active therapies, despite strong evidence that hypomethylating agents and lenalidomide significantly reduce transfusion burden. Other unmet needs identified by epidemiologic studies include high need for treatment options after failing first-line therapy and shared decision making by older MDS patients.
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.
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.
Targeted next-generation sequencing in myelodysplastic syndromes and prognostic interaction between mutations and IPSS-R. [2021]A 27-gene panel was used for next-generation sequencing (NGS) in 179 patients (median age 73 years) with primary myelodysplastic syndromes (MDS); risk distribution according to the revised International Prognostic Scoring System (IPSS-R) was 11% very high, 18% high, 17% intermediate, 38% low and 16% very low. At least one mutation/variant was detected in 147 (82%) patients; 23% harbored three or more mutations/variants. The most frequent mutations/variants included ASXL1 (30%), TET2 (25%), SF3B1 (20%), U2AF1 (16%), SRSF2 (16%), TP53 (13%), RUNX1 (11%), and DNMT3A (10%). At a median follow up of 30 months, 148 (83%) deaths and 26 (15%) leukemic transformations were recorded. Multivariable analysis of mutations/variants identified ASXL1 (HR 1.7, 95% CI 1.2-2.5), SETBP1 (HR 4.1, 95% CI 1.6-10.2) and TP53 (HR 2.2, 95% CI 1.3-3.4) as risk factors for overall and SRSF2 (HR 3.9, 95% CI 1.5-10.2), IDH2 (HR 3.7, 95% CI 1.2-11.4), and CSF3R (HR 6.0, 95% CI 1.6-22.6) for leukemia-free survival. Addition of age to the multivariable model did not affect these results while accounting for IPSS-R weakened the significance of TP53 mutations/variants (P = .1). An apparently favorable survival impact of SF3B1 mutations was no longer evident after adjustment for IPSS-R. Approximately 41% and 20% of patients harbored at least one adverse mutation/variant for overall and leukemia-free survival, respectively. Number of mutations/variants did not provide additional prognostic value. The survival impact of adverse mutations was most evident in IPSS-R very low/low risk patients. These observations suggest that targeted NGS might assist in treatment decision-making in lower risk MDS.
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.
Outcome of Myelodysplastic Syndromes Over Time in the United States: A National Cancer Data Base Study From 2004-2013. [2020]To study the changes in overall outcome of patients with myelodysplastic syndromes (MDSs) after approval of several treatments.
How we manage adults with myelodysplastic syndrome. [2021]The prognosis in Myelodysplastic syndromes (MDS), although recently refined by molecular studies, remains largely based on conventional prognostic scores [International Prognostic Scoring System (IPSS), revised IPSS], classifying patients into "lower risk" MDS (LR-MDS) and "higher risk" MDS (HR-MDS). In LR-MDS, treatment mainly aims at improving cytopenias, principally anaemia, while in HR-MDS it aims at delaying disease progression and prolonging survival. In LR-MDS without deletion 5q, anaemia is generally treated first by erythropoietic stimulating factors, while second line treatments are currently not approved [lenalidomide, hypomethylating agents (HMA), luspatercept] or rarely indicated (antithymocyte globulin). Lenalidomide has major efficacy in LR-MDS with deletion 5q. Allogeneic stem cell transplantation (allo-SCT) is sometimes considered in LR-MDS, and iron chelation can be considered when multiple red blood cell transfusions are required. Allo-SCT is the only potentially curative treatment for HR-MDS; however, it is rarely applicable. It is generally preceded by intensive chemotherapy (IC) or HMA in patients with excess of marrow blasts (especially if >10%). In other patients, HMA can improve survival. The role of new drugs, including venetoclax or, in case of specific mutations, IDH1 or IDH2 inhibitors, is investigated. IC is mainly indicated as a bridge to allo-SCT, in the absence of unfavourable karyotype.
Efficacy of lenalidomide in myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and an extreme platelet count. [2020]Lenalidomide is efficient in reducing red blood cell transfusion dependency and markedly lowering platelet counts in MDS/MPN-RS-T in the context of major platelet counts.
Clinical Outcomes Based on Measurable Residual Disease Status in Patients with Core-Binding Factor Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis. [2020]Measurable residual disease (MRD) response during acute myeloid leukemia (AML) treatment is a gold standard for determining treatment strategy, especially in core-binding factor (CBL) AML. The aim of this study was to critically review the literature on MRD status in the CBF-AML to determine the overall impact of MRD status on clinical outcomes. Published studies in the MEDLINE and EMBASE databases from their inception up to 1 June 2019 were searched. The primary end-point was either overall survival (OS) or recurrence-free survival (RFS) between MRD negative and MRD positive CBF-AML patients. The secondary variable was cumulative incidence of relapse (CIR) between groups. Of the 736 articles, 13 relevant studies were included in this meta-analysis. The MRD negative group displayed more favorable recurrence-free survival (RFS) than those with MRD positivity, with a pooled odds ratio (OR) of 4.5. Moreover, OS was also superior in the MRD negative group, with a pooled OR of 7.88. Corroborating this, the CIR was statistically significantly lower in the MRD negative group, with a pooled OR of 0.06. The most common cutoff MRD level was 1 × 10-3. These results suggest that MRD assessment should be a routine investigation in clinical practice in this AML subset.
Post-induction MRD by FCM and GATA1-PCR are significant prognostic factors for myeloid leukemia of Down syndrome. [2021]Myeloid leukemia of Down syndrome (ML-DS) is associated with good response to chemotherapy, resulting in favorable outcomes. However, no universal prognostic factors have been identified to date. To clarify a subgroup with high risk of relapse, the role of minimal residual disease (MRD) was explored in the AML-D11 trial by the Japanese Pediatric Leukemia/Lymphoma Study Group. MRD was prospectively evaluated at after induction therapy and at the end of all chemotherapy, using flow cytometry (FCM-MRD) and GATA1-targeted deep sequencing (GATA1-MRD). A total of 78 patients were eligible and 76 patients were stratified to the standard risk (SR) group by morphology. In SR patients, FCM-MRD and GATA1-MRD after induction were positive in 5/65 and 7/59 patients, respectively. Three-year event-free survival (EFS) and overall survival (OS) rates were 95.0% and 96.7% in the FCM-MRD-negative population, and 60.0% and 80.0% in the positive population. Three-year EFS and OS rates were both 98.1% in the GATA1-MRD-negative population, and 57.1% and 71.4% in the positive population. Adjusted hazard ratios for associations of FCM-MRD with EFS were 14.67 (p = 0.01). Detection of MRD by either FCM or GATA1 after initial induction therapy represents a significant prognostic factor for predicting ML-DS relapse.
Current Therapy of the Patients with MDS: Walking towards Personalized Therapy. [2021]Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis, dysplasia and peripheral cytopenias. Nowadays, MDS therapy is selected based on risk. The goals of therapy are different in low-risk and high-risk patients. In low-risk MDS, the goal is to decrease transfusion needs and to increase the quality of life. Currently, available drugs for newly diagnosed low-risk MDS include growth factor support, lenalidomide and immunosuppressive therapy. Additionally, luspatercept has recently been added to treat patients with MDS with ring sideroblasts, who are not candidates or have lost the response to erythropoiesis-stimulating agents. Treatment of high-risk patients is aimed to improve survival. To date, the only currently approved treatments are hypomethylating agents and allogeneic stem cell transplantation. However, the future for MDS patients is promising. In recent years, we are witnessing the emergence of multiple treatment combinations based on hypomethylating agents (pevonedistat, magrolimab, eprenetapopt, venetoclax) that have proven to be effective in MDS, even those with high-risk factors. Furthermore, the approval in the US of an oral hypomethylating agent opens the door to exclusively oral combinations for these patients and their consequent impact on the quality of life of these patients. Relapsed and refractory patients remain an unmet clinical need. We need more drugs and clinical trials for this profile of patients who have a dismal prognosis.
Emerging Therapies for the Myelodysplastic Syndromes. [2023]Despite considerable advances in our understanding of the molecular and epigenetic underpinnings of the myelodysplastic syndromes (MDS), this diverse group of myeloid neoplasms remains a significant clinical challenge. Considerable barriers to timely development of effective therapy include the diverse molecular landscape encountered in MDS patients, the difficulty in translating specific molecular aberration into a clinically meaningful animal model, as well as challenges in patient recruitment into clinical trials. These speak to the need to discover efficacious novel therapeutic targets which would in turn translate into improved patient outcomes in terms of both survival and quality of life. In this review, we outline recently published data pertaining to therapeutic advances in TGF-β pathway inhibition, STAT3, Hedgehog signaling, and additional therapeutic venues being actively explored in MDS.