OBI-3424 for T-Cell Acute Lymphoblastic Leukemia

Recruiting at 117 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 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)

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 3

Duration: Up to 51 weeks

39 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well OBI-3424 works in treating patients with T-cell acute lymphoblastic leukemia that has come back (relapsed) or does not response to treatment (refractory). Drugs used in chemotherapy, such as OBI-3424, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. OBI-3424 may reduce the amount of leukemia in the body.

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.

What makes the drug OBI-3424 unique for treating T-cell acute lymphoblastic leukemia?

OBI-3424 is unique because it is a prodrug (a medication that is converted into an active form in the body) designed to target cancer cells with high levels of a specific enzyme, potentially offering a more targeted approach compared to traditional chemotherapy. ^{1 2 3 4 5}

Research Team

Anjali S Advani

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Treatment (AKR1C3-activated prodrug OBI-3424) Experimental Treatment 1 Intervention

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.

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+

Findings from Research

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 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]

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 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 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]

References

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

A case report of pediatric acute lymphoblastic leukemia with e8a2 BCR/ABL1 fusion transcript. [2022]

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

Outcome for Children and Young Adults With T-Cell ALL and Induction Failure in Contemporary Trials. [2023]

3. China 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]. [2020]

4. Italy 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. [2021]

5. England 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. [2023]