TRX103 for Blood Cancers

Recruiting at 4 trial locations

Overseen By Tr1X Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Tr1X, Inc.

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TRX-103 to determine its safety and tolerability for individuals with certain blood cancers, such as acute leukemia or myelodysplastic syndrome. It includes patients who have undergone a specific type of stem cell transplant from a mismatched donor. The trial aims to observe patient reactions to a single infusion of TRX-103 post-transplant. Suitable candidates have conditions like acute leukemia, weigh at least 35 kg, and have received a transplant from a mismatched donor. As a Phase 1 trial, this research seeks to understand how TRX-103 functions in humans, 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 information does not specify if you need to stop taking your current medications. However, if you have taken another investigational agent recently, you must wait 28 days or until the effects wear off before joining this trial.

Is there any evidence suggesting that TRX-103 is likely to be safe for humans?

Studies have shown some initial safety data for TRX-103. In early testing, the first two groups of patients experienced positive results regarding safety and the duration of the treatment's activity in the body. TRX-103 was generally well-tolerated by these patients, who did not report any major problems or side effects.

However, as a Phase 1 study, this marks the first time TRX-103 is being tested in humans. This phase focuses on assessing safety, so more data is needed to fully understand TRX-103's safety profile. As more participants join these studies, researchers will gain a clearer picture of any potential risks or side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for blood cancers, which often include chemotherapy, radiation, and targeted therapies, TRX-103 is unique because it is infused post-hematopoietic stem cell transplant (HSCT). This timing could potentially enhance the transplant's effectiveness and reduce relapse rates by providing support when the body is most receptive. Researchers are particularly excited about TRX-103 because it may offer a new approach to improving outcomes in patients who undergo HSCT, a critical procedure for many with blood cancers. This innovative strategy could represent a significant advancement in post-transplant care.

What evidence suggests that TRX-103 might be an effective treatment for blood cancers?

Research suggests that TRX-103, the investigational treatment in this trial, might help treat blood cancers by preventing graft-versus-host disease (GvHD). This treatment releases IL-10 and other substances that reduce harmful inflammation. TRX-103 controls the immune system, preventing it from attacking the patient's own body after a stem cell transplant. Early studies in similar conditions indicate that TRX-103 may help manage these immune responses. While more information is needed, this approach shows promise in reducing GvHD and aiding recovery after transplantation. ^{2 3 5 6 7}

Who Is on the Research Team?

Maria Grazia Roncarolo, MD

Principal Investigator

Tr1X, Inc.

Are You a Good Fit for This Trial?

This trial is for people with various blood cancers like leukemia who are undergoing a stem cell transplant from a donor that doesn't fully match their tissue type. They're testing if TRX-103 can prevent a common and serious complication called Graft-versus-Host Disease.

Inclusion Criteria

I have been diagnosed with a specific type of blood cancer.

I weigh at least 35 Kg.

I am over 65 and my health score is below 5 for a specific transplant procedure.

Exclusion Criteria

I tested positive for hepatitis B but don't currently have an active infection.

I have had TTP or HUS and cannot be treated with sirolimus.

I have had a bone marrow or stem cell transplant from a donor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

TRX-103 is infused one time post hematopoietic stem cell transplantation (HSCT)

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TRX-103

Trial Overview The study is looking at the safety of TRX-103 when given once after a mismatched stem cell transplant. It's an early-phase trial, meaning it's one of the first times this drug is being tested in humans to see how well they tolerate it.

How Is the Trial Designed?

Group I: TRX-103 Experimental Treatment 1 Intervention

TRX-103 will be infused on time post hematopoietic stem cell transplant (HSCT).

TRX-103 is already approved in United States for the following indications:

Approved in United States as TRX103 for:

• Prevention of Graft versus Host Disease (GvHD) in patients undergoing hematopoietic stem cell transplant (HSCT) for hematological malignancies
• Treatment-refractory Crohn's Disease

Who Is Running the Clinical Trial?

Tr1X, Inc.

Lead Sponsor

Trials

2

Recruited

60+

Published Research Related to This Trial

Troxacitabine, a novel dioxolane L-nucleoside analog, demonstrated significant antileukemic activity in patients with refractory acute myeloid leukemia (AML) and chronic myelogenous leukemia in blastic phase (CML-BP), with 2 complete remissions and 6 patients returning to chronic-phase disease out of 16 assessable patients with AML and CML-BP.

The treatment was associated with manageable side effects, primarily stomatitis and hand-foot syndrome, affecting 7% and 24% of patients respectively, indicating a relatively safe profile for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of troxacitabine, a novel dioxolane nucleoside analog, in patients with refractory leukemia. Giles, FJ., Garcia-Manero, G., Cortes, JE., et al.[2017]

In myelodysplastic syndrome (MDS), the levels of CD34(+)CD38(-)CD123(+) cells were found to be lower in low-grade cases compared to acute myeloid leukemia (AML), but similar in high-grade MDS, suggesting a potential link between these cells and disease severity.

The presence of CD34(+)CD38(-)CD123(+) cells in MDS is associated with various clinical factors, indicating they may serve as a marker for malignant clonal cells and could be targeted for therapy, similar to their role in AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased CD34+CD38 -CD123 + cells in myelodysplastic syndrome displaying malignant features similar to those in AML. Li, LJ., Tao, JL., Fu, R., et al.[2021]

The t(10;11)(p13;q14-21) chromosomal translocation leads to the formation of the CALM-AF10 fusion gene, which is associated with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).

The CALM-AF10 fusion protein appears to promote leukemia by impairing the differentiation of blood cells, potentially through the upregulation of HOXA cluster genes, indicating a specific mechanism of action in leukemogenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of CALM-AF10 gene fusion in acute leukemia. Caudell, D., Aplan, PD.[2021]

Endoglin (CD105) is expressed on most blasts from patients with acute myeloid leukemia (AML) and acute B-lymphoblastic leukemia (B-ALL), and targeting this receptor with the monoclonal antibody TRC105 shows promise in inhibiting leukemia progression, particularly in AML.

While TRC105 effectively prevented AML blast engraftment, it was less effective in B-ALL due to the shedding of soluble CD105; however, it still demonstrated potential when combined with reduced intensity myeloablation, suggesting a novel therapeutic approach for both types of leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endoglin: a novel target for therapeutic intervention in acute leukemias revealed in xenograft mouse models. Dourado, KMC., Baik, J., Oliveira, VKP., et al.[2021]

In a phase I study involving 26 patients with hepatocellular carcinoma (HCC), the combination of TRC105 and sorafenib was well tolerated, with a 21% overall response rate and a median overall survival of 15.5 months.

The treatment showed promising activity, particularly in patients with measurable disease, where the response rate increased to 25%, leading to the continuation of the study into a phase II trial to further evaluate its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and Preliminary Phase II Study of TRC105 in Combination with Sorafenib in Hepatocellular Carcinoma. Duffy, AG., Ma, C., Ulahannan, SV., et al.[2021]

Targeting the interleukin 3 receptor α chain (CD123) on leukemia stem cells has been explored as a treatment for various myeloid malignancies, but the success of these therapies has been limited, indicating a need for better patient selection criteria.

Understanding the patterns of CD123 expression and its biological significance is essential for improving the effectiveness of CD123-targeting therapies in hematologic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting CD123 in hematologic malignancies: identifying suitable patients for targeted therapy. Patnaik, MM., Mughal, TI., Brooks, C., et al.[2021]

Troxacitabine (Troxatyl) is a unique nucleoside analogue with anticancer properties, distinguished by its unnatural stereochemical configuration, which disrupts DNA synthesis and induces cell death.

Initial phase I and II clinical trials, along with preclinical studies, suggest that Troxacitabine has a broad spectrum of antineoplastic activity, making it a promising candidate for treating various hematological malignancies and solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Troxacitabine]. Gourdeau, H., Jolivet, J.[2014]

The combination of the hypomethylating agent decitabine (DAC) and the monoclonal antibody TRC105 shows a more durable anti-leukemic effect in a xenograft model of relapsed/refractory acute myeloid leukemia (AML) compared to DAC alone.

This combination therapy enhances reactive oxygen species (ROS) activity, which is linked to a reduction in leukemia burden, suggesting a potential new treatment strategy for AML patients that warrants further clinical evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic effect of TRC105 and decitabine combination in AML xenografts. Baik, J., Felices, M., Yingst, A., et al.[2021]

The combination of troxacitabine and araC (cytarabine) shows a synergistic effect in treating acute myelogenous leukemia, significantly delaying DNA synthesis recovery and improving survival rates in both in vitro and in vivo studies with leukemia cell lines and tumor-bearing mice.

In vivo experiments demonstrated that this combination increased median survival time by 17% compared to araC alone, without adding extra toxicity, suggesting a promising treatment option for patients with acute leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complementary antineoplastic activity of the cytosine nucleoside analogues troxacitabine (Troxatyl) and cytarabine in human leukemia cells. Bouffard, DY., Jolivet, J., Leblond, L., et al.[2014]

The VALOR study, involving 711 patients, showed that the combination of vosaroxin and cytarabine resulted in better complete remission rates and survival for older patients (≥60 years) with relapsed/refractory acute myeloid leukemia (AML) compared to placebo/cytarabine.

Vosaroxin demonstrated a safety profile similar to existing AML treatments, making it a promising option for older patients who often face poor outcomes due to comorbidities and unfavorable cytogenetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vosaroxin in relapsed/refractory acute myeloid leukemia: efficacy and safety in the context of the current treatment landscape. Sedov, V., Stuart, RK.[2020]

Citations

1. withpower.com withpower.com/trial/phase-1-leukemia-3-2024-c43a8

TRX103 for Blood Cancers This Phase 1 medical study run by Tr1X, Inc. is evaluating whether TRX-103 will have tolerable side effects & efficacy for patients with Blood Cancers, ...

2. cirm.ca.gov cirm.ca.gov/our-progress/awards/trx103-prevention-gvhd-patients-receiving-hla-mismatched-related-or-unrelated-allogeneic-hsct-treatment-hematologic-malignancies/

TRX103 for prevention of GvHD in patients receiving HLA ... TRX103 will suppress GvHD by secretion of IL-10 and other cytokines in target tissues and organs, as well as through the stimulation of production of de-novo ...

3. mskcc.org mskcc.org/cancer-care/clinical-trials/24-322

A Phase 1 Study of TRX103 in People With Blood Cancers ... The people in this study are having stem cell transplantation as a treatment for a blood cancer such as: Acute lymphocytic leukemia; Acute myeloid leukemia ...

4. delta.larvol.com delta.larvol.com/Products/?ProductId=67e7526a-2c81-4090-a3ee-f4e5b24a4511

TRX103 / Tr1X Development of allogeneic engineered type I regulatory T cells (TRX103) to modulate inflammation and pathogenic T cells in refractory Crohn's disease.

5. clinconnect.io clinconnect.io/trials/NCT06462365?queryID=ce43674d1e9f78ce013c&apos=8975

Prevention of GvHD in Participants With Hematological This clinical trial is studying a new treatment called TRX-103 for patients with certain blood cancers, like Acute Lymphoblastic Leukemia and Acute Myeloid ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2666636725004713

A Phase I, First in Human Open Label Study to Evaluate ... A Phase I, First in Human Open Label Study to Evaluate the Safety and Tolerability of TRX103 Cell Infusion in Subjects with Hematological Malignancies ...

7. biospace.com biospace.com/press-releases/tr1x-awarded-8-million-cirm-grant-to-support-trx103-phase-1-2a-clinical-trial-for-graft-versus-host-disease

Tr1X Awarded $8 Million CIRM Grant to Support TRX103 ... The Company has reported positive initial persistence and safety data in the first two patient cohorts, with additional data anticipated to be ...