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

Trial Summary

What is the purpose of this trial?

The purpose of this Phase 1, first in human open-label study is to assess the safety and tolerability of TRX-103 in patients with hematological malignancies undergoing HLA-mismatched related or unrelated hematopoietic stem cell transplantation (HSCT). It is anticipated that up to 36 Subjects will be enrolled during a 18-24 month enrollment period. TRX-103 will be infused one time post HSCT.

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.

What data supports the effectiveness of the drug TRX-103 for blood cancers?

Research on troxacitabine, a component similar to TRX-103, shows it has strong anti-cancer activity in leukemia, especially when combined with other drugs like cytarabine. This suggests that TRX-103 might also be effective in treating blood cancers. ^{1 2 3 4 5}

How is the drug TRX-103 different from other blood cancer treatments?

TRX-103 targets a specific receptor called endoglin (CD105), which is found on certain leukemia cells and is involved in blood vessel formation. This makes it unique because it can potentially prevent the growth of leukemia by blocking this receptor, especially when combined with other treatments. ^{6 7 8 9 10}

Research Team

Maria Grazia Roncarolo, MD

Principal Investigator

Tr1X, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

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]

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]

References

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

Therapeutic effect of TRC105 and decitabine combination in AML xenografts. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Phase II study of troxacitabine, a novel dioxolane nucleoside analog, in patients with refractory leukemia. [2017]

3. Germany pubmed.ncbi.nlm.nih.gov

Complementary antineoplastic activity of the cytosine nucleoside analogues troxacitabine (Troxatyl) and cytarabine in human leukemia cells. [2014]

4. France pubmed.ncbi.nlm.nih.gov

[Troxacitabine]. [2014]

5. England pubmed.ncbi.nlm.nih.gov

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

6. United States pubmed.ncbi.nlm.nih.gov

Phase I and Preliminary Phase II Study of TRC105 in Combination with Sorafenib in Hepatocellular Carcinoma. [2021]

7. Japan pubmed.ncbi.nlm.nih.gov

Increased CD34+CD38 -CD123 + cells in myelodysplastic syndrome displaying malignant features similar to those in AML. [2021]

8. England pubmed.ncbi.nlm.nih.gov

The role of CALM-AF10 gene fusion in acute leukemia. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Targeting CD123 in hematologic malignancies: identifying suitable patients for targeted therapy. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Endoglin: a novel target for therapeutic intervention in acute leukemias revealed in xenograft mouse models. [2021]