Tretinoin and Arsenic Trioxide With or Without Gemtuzumab Ozogamicin in Treating Patients With Previously Untreated Acute Promyelocytic Leukemia

Acute Promyelocytic Leukemia With PML-RARA Clinical Trial

Official title:

Phase II Study of Treatment of Acute Promyelocytic Leukemia (APL) With ATRA, Arsenic Trioxide and Gemtuzumab Ozogamicin (GO)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01409161
• Other study ID #: 2010-0981
• Secondary ID: NCI-2011-0276720
• Status: Recruiting
• Phase: Phase 2
• Start date: October 5, 2011
• Est. completion date: December 18, 2025

Study information

• Verified date: May 2024
• Source: M.D. Anderson Cancer Center
• Contact: Farhad Ravandi-Kashani
• Phone: 713-745-0394
• Email: fravandi[@]mdanderson.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies how well tretinoin and arsenic trioxide with or without gemtuzumab ozogamicin works in treating patients with previously untreated acute promyelocytic leukemia. Drugs used in chemotherapy, such as tretinoin and arsenic trioxide, 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. Immunotoxins, such as gemtuzumab ozogamicin, may find certain cancer cells and kill them without harming normal cells. Giving tretinoin and arsenic trioxide together with gemtuzumab ozogamicin may kill more cancer cells.

Description:

PRIMARY OBJECTIVES:

I. Assess whether a combination of all-trans retinoic acid (ATRA [tretinoin]), and arsenic trioxide (ATO) can produce long-term event-free survival in patients with low-risk untreated acute promyelocytic leukemia (APL).

II. Assess whether administration of gemtuzumab ozogamicin (GO) at the diagnosis in patients with high-risk APL (white blood cell [WBC] > 10,000) and if the WBC rises to > 10,000 after start of treatment (in patients with low-risk disease) will improve complete response (CR) rate without increasing toxicity in high-risk untreated APL.

OUTLINE:

INDUCTION: Patients receive tretinoin orally (PO) twice daily (BID), arsenic trioxide intravenously (IV) over 1-2 hours daily, and gemtuzumab ozogamicin IV over 2 hours once at weeks 1-4.

CONSOLIDATION: Patients achieving CR receive arsenic trioxide IV 5 days per week during weeks 1-4, 9-12, 17-20, and 25-28 and tretinoin PO BID for 2 weeks on and 2 weeks off. Treatment repeats every 8 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6-12 months.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 151
• Est. completion date: December 18, 2025
• Est. primary completion date: December 18, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years and older

Eligibility

Inclusion Criteria:

• A diagnosis of APL based on the presence of the PML-RAR-alpha fusion gene by cytogenetics, polymerase chain reaction (PCR), or POD test

• Ability to understand and the willingness to sign a written informed consent document indicating that they are aware of the investigational nature of the study

• Patients in whom therapy for APL was initiated on an emergent basis are eligible (patients may have already started treatment with ATRA, ATO, and/or one dose of idarubicin due to the urgency to start therapy early)

• Women of child-bearing potential must have a negative serum pregnancy test at screening; in addition to having a negative pregnancy test confirmed at screening, all female participants of childbearing potential must have a negative pregnancy test confirmed within 48 hours prior to dosing with the study drug

• All sexually active subjects (males and females of child-bearing potential) agree to use 2 effective methods of contraception for the duration of the study

Exclusion Criteria:

• Fridericia corrected QT (QTcF) interval on the electrocardiogram (EKG) greater than 480 milliseconds

• Patients with creatinine > 2.5 times upper limit of normal unless felt to be related the underlying leukemia by the treating physician or hemolysis or Gilbert's disease

• Patients with total bilirubin >= 2.0 times upper limit of normal unless felt to be related the underlying leukemia by the treating physician or hemolysis or Gilbert's disease

• Patients with alanine aminotransferase (ALT)/aspartate aminotransferase (AST) > 3 times upper limit of normal unless felt to be related the underlying leukemia by the treating physician or hemolysis or Gilbert's disease

Related Conditions & MeSH terms

• Acute Promyelocytic Leukemia With PML-RARA
• Leukemia
• Leukemia, Promyelocytic, Acute

Intervention

Drug:
• Arsenic Trioxide
Given IV
• Gemtuzumab Ozogamicin
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Tretinoin
Given PO

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas
United States	MD Anderson Regional Care Center-Katy	Houston	Texas
United States	MD Anderson Regional Care Center-Bay Area	Nassau Bay	Texas
United States	MD Anderson Regional Care Center-Sugar Land	Sugar Land	Texas
United States	MD Anderson Regional Care Center-The Woodlands	The Woodlands	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event free survival	Monitored using a Bayesian time-to-event model.	The time from the start of treatment to first documentation of disease relapse or death, assessed up to 2 years

External Links

•   M D Anderson Cancer Center