Tretinoin + Arsenic Trioxide for Acute Promyelocytic Leukemia

Not currently recruiting at 190 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Children's Oncology Group

Must be taking: ATRA, Hydroxyurea, Corticosteroids

Disqualifiers: Secondary APL, Prolonged QT, Pregnancy, others

No Placebo Group All 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 Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two drugs, tretinoin and arsenic trioxide, for treating newly diagnosed acute promyelocytic leukemia (APL), a type of blood cancer. The goal is to determine if these drugs can effectively treat APL while reducing the long-term side effects typically caused by standard chemotherapy. The trial seeks to eliminate or reduce the use of anthracyclines, a common chemotherapy drug that can harm the heart over time. Suitable candidates for this trial have a new diagnosis of APL confirmed by blood or bone marrow tests and have not received other chemotherapy treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients a chance to access potentially effective treatment early.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using tretinoin and arsenic trioxide together is generally safe for treating acute promyelocytic leukemia. Studies have found that this combination can lead to complete remission in 90%–100% of patients, indicating that many recover well with this treatment.

Long-term research indicates that this treatment is highly effective and has few side effects. However, a serious condition called differentiation syndrome can occur with arsenic trioxide, requiring careful management if it arises.

Overall, tretinoin and arsenic trioxide are usually well-tolerated, with some risks that doctors will monitor closely. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for acute promyelocytic leukemia?

Researchers are excited about using tretinoin and arsenic trioxide for treating Acute Promyelocytic Leukemia (APL) because these treatments offer a novel approach compared to traditional chemotherapy, which typically relies on anthracyclines. Tretinoin and arsenic trioxide target the leukemia at the genetic level, specifically addressing the PML-RARA fusion protein that is pivotal in APL. This targeted action not only helps in effectively reducing cancer cells but also tends to have a more favorable side effect profile than conventional chemotherapy. Additionally, the combination of tretinoin with arsenic trioxide has shown potential for quicker and more sustained remission, which could significantly improve patient outcomes.

What evidence suggests that tretinoin and arsenic trioxide might be an effective treatment for acute promyelocytic leukemia?

Studies have shown that using tretinoin and arsenic trioxide together effectively treats acute promyelocytic leukemia (APL). In this trial, participants will receive a combination of tretinoin and arsenic trioxide, which research from the APOLLO trial suggested works well for newly diagnosed patients with high-risk APL. This method has proven very effective and causes fewer blood-related side effects compared to traditional chemotherapy. Additionally, this combination has been found to be as effective as chemotherapy but without severe long-term side effects like heart damage. This makes it a promising option for those seeking effective treatment with fewer risks. ^{5 6 7 8 9}

Who Is on the Research Team?

Matthew A Kutny

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

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.

Exclusion Criteria

Lactating females who plan to breastfeed their infants are excluded

Patients with right bundle branch block plus left anterior hemiblock, bifascicular block are excluded

My heart's electrical cycle length is within a safe range.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Arsenic Trioxide
• Tretinoin

Trial Overview The 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.

How Is the Trial Designed?

Group I: Treatment (tretinoin, arsenic trioxide, chemotherapy) Experimental Treatment 9 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)

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+

Published Research Related to This Trial

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New data with arsenic trioxide in leukemias and myelodysplastic syndromes. Sekeres, MA.[2019]

Arsenic trioxide (ATO) showed a complete remission (CR) rate of 97.5% in 41 patients with acute promyelocytic leukemia (APL), which is comparable to the 93.3% CR rate seen with all-trans retinoic acid (ATRA) in 30 patients.

ATO therapy resulted in a significantly shorter median time to complete remission (29 days) compared to ATRA (38.5 days), and ATRA was associated with a high incidence of retinoic acid syndrome (52.9%), suggesting ATO may be a safer and more effective first-line treatment for APL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of efficacy and adverse effects between arsenic trioxide and all-trans retinoic acid in patients with acute promyelocytic leukemia]. Jiao, L., Wang, SJ., Zhuang, JL., 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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Arsenicals in hematologic cancers. Novick, SC., Warrell, RP.[2018]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40825164/

Arsenic Trioxide and All-Trans Retinoic Acid Combination ... The results of the APOLLO trial support the use of ATO and ATRA for the treatment of newly diagnosed patients with high-risk APL.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02339740

NCT02339740 | Tretinoin and Arsenic Trioxide in Treating ... This phase III trial studies tretinoin and arsenic trioxide in treating patients with newly diagnosed acute promyelocytic leukemia.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1300874

Retinoic Acid and Arsenic Trioxide for Acute Promyelocytic ... Pilot studies of treatment with arsenic trioxide with or without ATRA have shown high efficacy and reduced hematologic toxicity. Methods. We ...

4. esmo.org esmo.org/oncology-news/arsenic-trioxide-in-combination-with-all-trans-retinoic-acid-for-the-treatment-of-newly-diagnosed-patients-with-high-risk-apl

Arsenic Trioxide in Combination with All-Trans Retinoic ... APOLLO is a pan-European academic randomised study that prospectively compared the efficacy of arsenic trioxide in combination with all-trans ...

5. nature.com nature.com/articles/s41408-022-00753-y

An effective and chemotherapy-free strategy of all-trans ... The combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has been demonstrated to have comparable effectiveness or ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5359123/

Retinoic acid and arsenic trioxide in the treatment of acute ... All-trans retinoic acid and arsenic trioxide, with chemotherapy limited to patients with high-risk disease, has led to complete remission in 90%–100% of ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02339740

NCT02339740 | Tretinoin and Arsenic Trioxide in Treating ... This phase III trial studies tretinoin and arsenic trioxide in treating patients with newly diagnosed acute promyelocytic leukemia.

8. pnas.org pnas.org/doi/10.1073/pnas.0813280106

Long-term efficacy and safety of all-trans retinoic acid ... These results demonstrate the high efficacy and minimal toxicity of ATRA/ATO treatment for newly diagnosed APL in long-term follow-up.

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2019/021248s018lbl.pdf

Trisenox - accessdata.fda.gov Differentiation syndrome, which may be life-threatening or fatal, has been observed in patients with acute promyelocytic leukemia (APL) treated with TRISENOX.