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

NCT01409161 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2010-0981NCI-2011-02767
• Study Type: interventional
• Target: 151
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Acute Promyelocytic Leukemia With PML-RARA

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

Treatment (tretinoin, arsenic trioxide, gemtuzumab ozogamicin)

EXPERIMENTAL

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.

Drug: Arsenic Trioxide; Drug: Gemtuzumab Ozogamicin; Other: Laboratory Biomarker Analysis; Drug: Tretinoin

Interventions

Arsenic Trioxide DRUG

Given IV

Also known as: Arsenic (III) Oxide, Arsenic Sesquioxide, Arsenous Acid, Arsenous Acid Anhydride, Arsenous Oxide, Trisenox, White Arsenic

Treatment (tretinoin, arsenic trioxide, gemtuzumab ozogamicin)

Gemtuzumab Ozogamicin DRUG

Given IV

Also known as: Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody, CDP-771, CMA-676, gemtuzumab, hP67.6-Calicheamicin, Mylotarg, WAY-CMA-676

Treatment (tretinoin, arsenic trioxide, gemtuzumab ozogamicin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (tretinoin, arsenic trioxide, gemtuzumab ozogamicin)

Tretinoin DRUG

Given PO

Also known as: 2,4,6,8-Nonatetraenoic acid, 3, 7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-, (all-E)-, Aberel, Airol, Aknoten, all trans-Retinoic acid, All-trans Retinoic Acid, All-trans Vitamin A Acid, all-trans-Retinoic acid, all-trans-Vitamin A acid, ATRA, Avita, beta-Retinoic Acid, Cordes Vas, Dermairol, Epi-Aberel, Eudyna, Renova, Retin-A, Retin-A MICRO, Retin-A-Micro, retinoic acid, Retisol-A, Ro 5488, Stieva-A, Stieva-A Forte, Trans Retinoic Acid, Trans Vitamin A Acid, trans-Retinoic acid, Tretinoinum, Vesanoid, vitamin A acid, Vitamin A acid, all-trans-, Vitinoin

Treatment (tretinoin, arsenic trioxide, gemtuzumab ozogamicin)

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

MD Anderson Regional Care Center-Katy

Houston, Texas, 77094, United States

RECRUITING

MD Anderson Regional Care Center-Bay Area

Nassau Bay, Texas, 77058, United States

RECRUITING

MD Anderson Regional Care Center-Sugar Land

Sugar Land, Texas, 77478, United States

RECRUITING

MD Anderson Regional Care Center-The Woodlands

The Woodlands, Texas, 77384, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 39584789 DERIVED

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Promyelocytic, Acute

Interventions

Arsenic Trioxide; arsenous acid; Gemtuzumab; Tretinoin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid, Acute; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds; Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors

Study Officials

• Farhad Ravandi-Kashani

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Farhad Ravandi-Kashani

CONTACT

713-745-0394; fravandi@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2011
• First Posted: August 4, 2011
• Study Start: October 5, 2011
• Primary Completion (Estimated): December 18, 2027
• Study Completion (Estimated): December 18, 2027
• Last Updated: May 5, 2026

Record last verified: 2025-12

Locations

US (5)