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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Promyelocytic Leukemia With PML-RARA
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Gemtuzumab Ozogamicin; Drug: Arsenic Trioxide; Drug: Tretinoin

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 151
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Farhad Ravandi-Kashani; Phone Number: 713-745-0394; Email: fravandi@mdanderson.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • M D Anderson Cancer Center
      • Contact: Farhad Ravandi-Kashani; Phone Number: 713-745-0394
      • Principal Investigator: Farhad Ravandi-Kashani
    • Houston, Texas, United States, 77094
      • Recruiting
      • MD Anderson Regional Care Center-Katy
      • Contact: Farhad Ravandi-Kashani; Phone Number: 713-745-0394
      • Principal Investigator: Farhad Ravandi-Kashani
    • Nassau Bay, Texas, United States, 77058
      • Recruiting
      • MD Anderson Regional Care Center-Bay Area
      • Contact: Farhad Ravandi-Kashani; Phone Number: 713-745-0394
      • Principal Investigator: Farhad Ravandi-Kashani
    • Sugar Land, Texas, United States, 77478
      • Recruiting
      • MD Anderson Regional Care Center-Sugar Land
      • Contact: Farhad Ravandi-Kashani; Phone Number: 713-745-0394
      • Principal Investigator: Farhad Ravandi-Kashani
    • The Woodlands, Texas, United States, 77384
      • Recruiting
      • MD Anderson Regional Care Center-The Woodlands
      • Contact: Farhad Ravandi-Kashani; Phone Number: 713-745-0394
      • Principal Investigator: Farhad Ravandi-Kashani

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (tretinoin, arsenic trioxide, gemtuzumab ozogamicin); INDUCTION: Patients receive tretinoin PO BID, arsenic trioxide 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.

Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Gemtuzumab Ozogamicin; Given IV; Other Names: Mylotarg; Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody; CDP-771; CMA-676; gemtuzumab; hP67.6-Calicheamicin; WAY-CMA-676; Drug: Arsenic Trioxide; Given IV; Other Names: Arsenic (III) Oxide; Arsenic Sesquioxide; Arsenous Acid Anhydride; Trisenox; Arsenous Acid; Arsenous Oxide; White Arsenic; Drug: Tretinoin; Given PO; Other Names: Vesanoid; ATRA; Renova; Retin-A; Airol; Avita; Stieva-A; 2,4,6,8-Nonatetraenoic acid, 3, 7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-, (all-E)-; Aberel; Aknoten; all trans-Retinoic acid; All-trans Retinoic Acid; All-trans Vitamin A Acid; all-trans-Retinoic acid; all-trans-Vitamin A acid; beta-Retinoic Acid; Cordes Vas; Dermairol; Epi-Aberel; Eudyna; Retin-A MICRO; Retin-A-Micro; Retisol-A; Ro 5488; Stieva-A Forte; Trans Retinoic Acid; Trans Vitamin A Acid; Tretinoinum; Vitamin A acid, all-trans-; Vitinoin; retinoic acid; trans-Retinoic acid; vitamin A acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Farhad Ravandi-Kashani, M.D. Anderson Cancer Center

Publications and helpful links

General Publications

• Jen WY, Marvin-Peek J, Kantarjian HM, Alvarado Y, Borthakur G, Jabbour E, Wierda W, Kadia TM, Daver NG, DiNardo CD, Short NJ, Jain N, Ferrajoli A, Kornblau S, Yilmaz M, Ohanian M, McCue D, Burger J, Hammond D, Patel K, Issa GC, Pemmaraju N, Sasaki K, Maiti A, Abbas HA, Chien K, Takahashi K, Haddad F, Bose P, Masarova L, Montalban-Bravo G, Swaminathan M, Brandt M, Pierce S, Garcia-Manero G, Ravandi F. Long-term follow-up of a phase 2 study of all-trans retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin in acute promyelocytic leukemia. Cancer. 2025 Jan 1;131(1):e35662. doi: 10.1002/cncr.35662. Epub 2024 Nov 25.

Helpful Links

• M D Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2011
• Primary Completion (Estimated): December 18, 2027
• Study Completion (Estimated): December 18, 2027

Study Registration Dates

• First Submitted: August 2, 2011
• First Submitted That Met QC Criteria: August 2, 2011
• First Posted (Estimated): August 4, 2011

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Leukemia, Myeloid, Acute; Hemic and Lymphatic Diseases; Leukemia, Promyelocytic, Acute; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological; Biological Factors; Carbohydrates; Glycosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Inorganic Chemicals; Diterpenes; Aminoglycosides; Oxides; Oxygen Compounds; Calicheamicins; Vitamin A; Arsenicals; Arsenic Trioxide; Gemtuzumab; Tretinoin; arsenous acid
• Other Study ID Numbers: 2010-0981 (Other Identifier: M D Anderson Cancer Center); NCI-2011-02767 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No