OBI-3424 for T-Cell Acute Lymphoblastic Leukemia

Recruiting at 169 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: SWOG Cancer Research Network

Must not be taking: Chemotherapy, Investigational agents

Disqualifiers: Pregnancy, Active infections, Recent transplant, 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: 3

Duration: Up to 51 weeks

67 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safety and effectiveness of a new chemotherapy drug, OBI-3424, for patients with T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma that has returned or is not responding to traditional treatments. OBI-3424 stops cancer cells from growing and spreading. The trial will monitor how well this drug reduces leukemia in the body. People battling relapsed or treatment-resistant T-cell leukemia or lymphoma, with evidence of acute leukemia in their blood or bone marrow, might be a good fit for this trial. As a Phase 1, Phase 2 trial, this research focuses on understanding how OBI-3424 works in people and measuring its effectiveness in an initial, smaller group. Participants have the opportunity to be among the first to benefit from this promising treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have had chemotherapy or investigational agents within 14 days before joining, except for certain drugs like steroids and some oral medications. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that OBI-3424 is likely to be safe for humans?

Research has shown that OBI-3424 is generally well-tolerated by patients. Some studies observed side effects like low blood platelet levels and anemia, but these were dose-related and did not worsen over time. The recommended dose is 12 mg/m² every three weeks. Thus, while some side effects exist, they remain manageable and do not increase with repeated treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard chemotherapy treatments for T-cell acute lymphoblastic leukemia, OBI-3424 is an experimental prodrug specifically activated by the enzyme AKR1C3, which is often overexpressed in cancer cells. This targeted approach means OBI-3424 can selectively attack cancer cells while sparing healthy ones, potentially reducing harmful side effects associated with traditional chemotherapy. Researchers are excited because this novel mechanism of action could offer a more effective and less toxic treatment option, especially for patients who haven't responded well to existing therapies.

What evidence suggests that OBI-3424 might be an effective treatment for T-cell acute lymphoblastic leukemia?

Research has shown that OBI-3424, the investigational treatment studied in this trial, yields promising results in treating T-cell acute lymphoblastic leukemia (T-ALL) in early tests. Studies have found that this drug, activated by a specific enzyme, effectively combats aggressive forms of T-ALL. OBI-3424 targets cancer cells, preventing their growth and spread. Initial findings suggest it may benefit patients whose leukemia has returned or does not respond to other treatments. This offers hope that OBI-3424 could become a strong option for treating this challenging condition. ^{1 4 6 7 8}

Who Is on the Research Team?

Anjali S Advani

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

Adults diagnosed with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) who have at least 5% lymphoblasts in blood or bone marrow, and no central nervous system disease. They must be over 18, with adequate kidney and liver function, not pregnant or nursing, and willing to use contraception. Excluded are those recently receiving certain chemotherapies, post-allogeneic transplant patients within 90 days, individuals with uncontrolled infections or severe graft versus host disease.

Inclusion Criteria

I have chronic hepatitis B but my viral load is undetectable or I am on treatment.

Prothrombin time (PT)/partial thromboplastin time (PTT)/fibrinogen (as clinically indicated) (within 14 days prior to registration to obtain baseline measurements)

I can take care of myself but may not be able to do heavy physical work.

Exclusion Criteria

I haven't had chemotherapy in the last 14 days, except for certain allowed medications.

I do not have an uncontrolled infection.

I am not pregnant or nursing and will use effective birth control during and up to 6 months after treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AKR1C3-activated prodrug OBI-3424 intravenously over 30 minutes on days 1 and 8, with treatment repeating every 21 days for up to 17 cycles

Up to 51 weeks

2 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 5 years

Monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• OBI-3424

Trial Overview The trial is testing OBI-3424's effectiveness for T-ALL that has returned after treatment or hasn't responded to it. OBI-3424 is a chemotherapy drug designed to kill cancer cells by preventing them from growing and spreading.

How Is the Trial Designed?

Group I: Treatment (AKR1C3-activated prodrug OBI-3424) Experimental Treatment 5 Interventions

Patients receive AKR1C3-activated prodrug OBI-3424 IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients who have not achieved a PR by the 4th cycle of treatment are removed from the study (unless clinically benefitting in the opinion of the treating investigator).Patients undergo blood sample collection during screening and CSF sample collection on study. Patients also undergo bone marrow aspirate or core biopsy and may undergo CT scan throughout the study.

OBI-3424 is already approved in United States for the following indications:

Approved in United States as OBI-3424 for:

• Orphan Drug Designation for T-cell acute lymphoblastic leukemia (T-ALL)
• Orphan Drug Designation for Hepatocellular Carcinoma (HCC)

Who Is Running the Clinical Trial?

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

A pediatric patient with a rare atypical BCR/ABL1 e8a2 fusion transcript achieved complete remission from Ph+ B-cell precursor acute lymphoblastic leukemia after 33 days of treatment, highlighting the potential for effective outcomes even with uncommon genetic variants.

The study emphasizes the importance of genetic evaluation in diagnosing acute lymphoblastic leukemia, using methods like fluorescent in situ hybridization and PCR to detect rare BCR/ABL1 transcripts, which can guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case report of pediatric acute lymphoblastic leukemia with e8a2 BCR/ABL1 fusion transcript. Mroczkowska, A., Jaźwiec, B., Urbańska-Rakus, J., et al.[2022]

In a phase 2 trial involving 349 patients with newly diagnosed T-cell acute lymphoblastic leukaemia, the ALL-T11 protocol achieved a high 3-year event-free survival rate of 86.4% and an overall survival rate of 91.3%, indicating effective treatment outcomes with reduced reliance on cranial radiotherapy and stem cell transplantation.

The study demonstrated that the addition of nelarabine and intensified L-asparaginase therapy led to a high complete remission rate of 89%, while the treatment was associated with manageable side effects, including a low incidence of severe neuropathy and febrile neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nelarabine, intensive L-asparaginase, and protracted intrathecal therapy for newly diagnosed T-cell acute lymphoblastic leukaemia in children and young adults (ALL-T11): a nationwide, multicenter, phase 2 trial including randomisation in the very high-risk group. Sato, A., Hatta, Y., Imai, C., et al.[2023]

In a study of 46 patients with ABL-class fusion positive precursor B-cell acute lymphoblastic leukemia, a significant number showed poor early treatment responses, with 71.4% having high levels of minimal residual disease after initial treatment.

The addition of tyrosine kinase inhibitors (TKIs) to treatment improved outcomes, as only 1 out of 13 patients receiving TKIs relapsed compared to 8 out of 33 patients who did not receive TKIs, highlighting the potential benefit of TKIs in this challenging subtype of leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relapses and treatment-related events contributed equally to poor prognosis in children with ABL-class fusion positive B-cell acute lymphoblastic leukemia treated according to AIEOP-BFM protocols. Cario, G., Leoni, V., Conter, V., et al.[2021]

In a study of 89 patients with BCR-ABL positive acute lymphoblastic leukemia, second-generation tyrosine kinase inhibitors (TKIs) like dasatinib showed significantly better overall survival (64.0% vs. 34.9%) and relapse-free survival (55.0% vs. 17.2%) compared to first-generation TKIs like imatinib.

Both first-generation and second-generation TKIs had similar rates of complete remission and complete molecular remission, but achieving complete molecular remission was identified as a key favorable prognostic factor for overall survival and relapse-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of clinical efficacy between first-generation and second-generation tyrosine kinase inhibitors based regimen in the treatment of patients with BCR-ABL positive acute lymphoblastic leukemia]. Liu, Y., Mi, RH., Chen, L., et al.[2020]

In a study of 325 patients aged 21 and younger with T-cell acute lymphoblastic leukemia (T-ALL) who experienced induction failure, the 10-year overall survival rate improved to 54.7% with contemporary therapies, compared to just 27.6% in historical cohorts from 1985 to 2000.

Among patients who achieved complete remission after induction, those who underwent allogeneic hematopoietic stem cell transplantation (HSCT) had significantly better disease-free survival rates (63.8%) compared to those who did not receive a transplant (45.5%), highlighting the potential benefit of HSCT in improving outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome for Children and Young Adults With T-Cell ALL and Induction Failure in Contemporary Trials. Raetz, EA., Rebora, P., Conter, V., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04315324

Study to Test OBI-3424 in Patients With T-Cell Acute ... This phase I/II trial studies the safety, side effects and best dose of OBI-3424 and how well it works in treating patients with T-cell acute lymphoblastic ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31015346/

OBI-3424, a Novel AKR1C3-Activated Prodrug, Exhibits ... OBI-3424 exerted profound in vivo efficacy against T-ALL PDXs derived predominantly from aggressive and fatal disease, and therefore may ...

3. aacrjournals.org aacrjournals.org/clincancerres/article/25/14/4493/81788/OBI-3424-a-Novel-AKR1C3-Activated-Prodrug-Exhibits

OBI-3424, a Novel AKR1C3-Activated Prodrug, Exhibits ... In this study we investigated the efficacy of a novel prodrug, OBI-3424, in preclinical models of pediatric acute lymphoblastic leukemia (ALL). OBI-3424 is ...

4. nature.com nature.com/articles/s41416-023-02280-4

Phase 1 dose-escalation study evaluating the safety ... The RP2D is 12 mg/m 2 once every 3 weeks. OBI-3424 was well tolerated; dose-dependent, noncumulative thrombocytopenia and anemia were dose-limiting.

5. swog.org swog.org/patients/trials-open-patients/testing-drug-obi-3424-people-t-cell-acute-lymphoblastic-leukemia-or-t

Testing the Drug OBI-3424 in People with T-Cell Acute ... This trial is testing a new medicine, called OBI-3424, in people with T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6635081/

OBI-3424, a novel AKR1C3-activated prodrug, exhibits potent ... OBI-3424 is a highly selective prodrug that is converted by aldo-keto reductase family 1 member C3 (AKR1C3) to a potent DNA alkylating agent.

7. uchicagomedicine.org uchicagomedicine.org/find-a-clinical-trial/clinical-trial/cirb210385

CLINICAL TRIAL / NCT04315324 This phase I/II trial studies the safety, side effects and best dose of OBI-3424 and how well it works in treating patients with T-cell acute lymphoblastic ...

8. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_1/7050/760569/Abstract-7050-Preclinical-evaluation-of-the-AKR1C3

Abstract 7050: Preclinical evaluation of the AKR1C3-activated ... We evaluated the anti-tumor activity of OBI-3424 across a panel of hepatoblastoma PDXs and examined AKR1C3 expression as a response biomarker.