158 Participants Needed

Tretinoin + Arsenic Trioxide for Acute Promyelocytic Leukemia

Recruiting at 183 trial locations
Age: < 65
Sex: Any
Trial Phase: Phase 3
Sponsor: Children's Oncology Group
Must be taking: ATRA, Hydroxyurea, Corticosteroids
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

This phase III trial studies tretinoin and arsenic trioxide in treating patients with newly diagnosed acute promyelocytic leukemia. Standard treatment for acute promyelocytic leukemia involves high doses of a common class of chemotherapy drugs called anthracyclines, which are known to cause long-term side effects, especially to the heart. Tretinoin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Arsenic trioxide may stop the growth of cancer cells by either killing the cells, by stopping them from dividing, or by stopping them from spreading. Completely removing or reducing the amount of anthracycline chemotherapy and giving tretinoin together with arsenic trioxide may be an effective treatment for acute promyelocytic leukemia and may reduce some of the long-term side effects.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you can continue taking hydroxyurea, corticosteroids, and intrathecal cytarabine before starting the trial treatment.

What data supports the effectiveness of the drug combination of Tretinoin and Arsenic Trioxide for treating Acute Promyelocytic Leukemia?

Research shows that combining arsenic trioxide with tretinoin can lead to complete remission in over 80% of patients with relapsed acute promyelocytic leukemia, and it is effective in newly diagnosed cases as well, providing excellent survival outcomes.12345

Is the combination of Tretinoin and Arsenic Trioxide safe for humans?

The combination of Tretinoin (all-trans retinoic acid) and Arsenic Trioxide has been studied for treating acute promyelocytic leukemia and is generally well tolerated. Common side effects include fatigue, rash, fluid retention, and changes in heart rhythm, but it is considered relatively safe at the doses used for this condition.45678

What makes the drug combination of Tretinoin and Arsenic Trioxide unique for treating acute promyelocytic leukemia?

This drug combination is unique because it uses both Tretinoin and Arsenic Trioxide together to target acute promyelocytic leukemia, aiming to reduce relapse rates by combining their different mechanisms: Tretinoin helps immature blood cells mature, while Arsenic Trioxide induces cell death in cancerous cells. This approach is different from traditional treatments that typically use Tretinoin with chemotherapy and reserve Arsenic Trioxide for relapsed cases.126910

Research Team

MA

Matthew A Kutny

Principal Investigator

Children's Oncology Group

Eligibility Criteria

This trial is for patients newly diagnosed with acute promyelocytic leukemia (APL), confirmed by bone marrow or blood tests, and who have the PML-RARalpha transcript. They can't have had previous APL treatments except certain steroids, hydroxyurea, or up to 5 days of ATRA. Pregnant women, breastfeeding mothers, those with heart issues like prolonged QT syndrome or significant arrhythmias are excluded.

Inclusion Criteria

I don't need a lumbar puncture to join the study, even if I have CNS symptoms.
My sample for testing will come from bone marrow, but if not possible, blood will be used.
My test shows I have the PML-RARalpha gene change.
See 6 more

Exclusion Criteria

Lactating females who plan to breastfeed their infants are excluded
My heart's electrical cycle length is within a safe range.
I do not have a history of serious irregular heartbeats.
See 8 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Patients receive tretinoin and arsenic trioxide, with additional treatments for high-risk patients, to achieve hematologic complete remission

Up to 70 days
Daily visits for treatment administration

Consolidation Therapy

Patients receive tretinoin and arsenic trioxide in cycles to consolidate remission

Up to 168 days (3 courses of 56 days each)
Multiple visits per cycle for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 years
Monthly for 12 months, every 3 months for 36 months, every 6 months for 48 months, then annually for 2 years

Treatment Details

Interventions

  • Arsenic Trioxide
  • Tretinoin
Trial OverviewThe study is testing tretinoin and arsenic trioxide as a treatment for new acute promyelocytic leukemia cases. It aims to see if this combination reduces long-term side effects compared to traditional chemotherapy drugs known as anthracyclines that can affect the heart.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (tretinoin, arsenic trioxide, chemotherapy)Experimental Treatment9 Interventions
See Detailed Description

Arsenic Trioxide is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Trisenox for:
  • Acute promyelocytic leukemia (APL)
🇪🇺
Approved in European Union as Trisenox for:
  • Acute promyelocytic leukemia (APL)

Find a Clinic Near You

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials
467
Recruited
241,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Findings from Research

Arsenic trioxide is highly effective in treating acute promyelocytic leukemia (APL), achieving complete remissions in over 80% of relapsed patients and molecular remission in 90% of those who reach complete remission.
Clinical trials indicate that arsenic trioxide not only benefits relapsed APL patients but also shows promise in first-line treatment and consolidation therapy, improving event-free and overall survival rates.
New data with arsenic trioxide in leukemias and myelodysplastic syndromes.Sekeres, MA.[2019]
In a study of 20 patients with acute promyelocytic leukemia (APL), the combination of all-trans retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)) resulted in a high complete remission (CR) rate of 94.4%, with 17 out of 18 evaluable patients achieving CR.
The treatment was well-tolerated, showing no significant side effects, indicating that this combination therapy is both effective and safe for APL patients.
[Preliminary observation of the combination of arsenic trioxide and all-trans retinoic acid for the treatment of acute promyelocytic leukemia].Zhao, YZ., Li, HQ., Li, DP., et al.[2018]
Arsenic trioxide (AT) has shown high efficacy in treating acute promyelocytic leukemia (APL), achieving complete remission in 80% to 90% of patients with refractory or relapsed cases, while being well tolerated at a dose of 0.15 mg/kg/d.
Common side effects include fatigue, rash, and QTc-interval prolongation, but ongoing research is exploring its combination with retinoic acid and potential use in other blood cancers and solid tumors.
Arsenicals in hematologic cancers.Novick, SC., Warrell, RP.[2018]

References

Use of arsenic trioxide in remission induction and consolidation therapy for acute promyelocytic leukaemia in the Australasian Leukaemia and Lymphoma Group (ALLG) APML4 study: a non-randomised phase 2 trial. [2018]
New data with arsenic trioxide in leukemias and myelodysplastic syndromes. [2019]
Oral Arsenic Regimen for APL Deemed "Revolutionary". [2023]
[Therapeutic effects of combination of arsenic trioxide with low-dose all-trans retinoic acid on induction of remission acute promyeloeytic leukemia]. [2018]
United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. [2022]
[Preliminary observation of the combination of arsenic trioxide and all-trans retinoic acid for the treatment of acute promyelocytic leukemia]. [2018]
Arsenicals in hematologic cancers. [2018]
[Comparison of efficacy and adverse effects between arsenic trioxide and all-trans retinoic acid in patients with acute promyelocytic leukemia]. [2018]
[Arsenic trioxide, a new drug for the treatment of acute promyelocytic leukemia resistant to tretinoine]. [2018]
Long term curative effects of sequential therapy with all-trans retinoic acid, arsenious oxide and chemotherapy on patients with acute promyelocytic leukemia. [2018]