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

NCT ID: NCT01409161

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

151 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-10-05

Study Completion Date

2027-12-18

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Acute Promyelocytic Leukemia With PML-RARA

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Arsenic Trioxide

Intervention Type DRUG

Given IV

Gemtuzumab Ozogamicin

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Tretinoin

Intervention Type DRUG

Given PO

Interventions

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Arsenic Trioxide

Given IV

Intervention Type DRUG

Gemtuzumab Ozogamicin

Given IV

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Tretinoin

Given PO

Intervention Type DRUG

Other Intervention Names

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Arsenic (III) Oxide Arsenic Sesquioxide Arsenous Acid Arsenous Acid Anhydride Arsenous Oxide Trisenox White Arsenic Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody CDP-771 CMA-676 gemtuzumab hP67.6-Calicheamicin Mylotarg WAY-CMA-676 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

Eligibility Criteria

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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
Minimum Eligible Age

10 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Farhad Ravandi-Kashani

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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M D Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

MD Anderson Regional Care Center-Katy

Houston, Texas, United States

Site Status RECRUITING

MD Anderson Regional Care Center-Bay Area

Nassau Bay, Texas, United States

Site Status RECRUITING

MD Anderson Regional Care Center-Sugar Land

Sugar Land, Texas, United States

Site Status RECRUITING

MD Anderson Regional Care Center-The Woodlands

The Woodlands, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Farhad Ravandi-Kashani

Role: CONTACT

713-745-0394

Facility Contacts

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Farhad Ravandi-Kashani

Role: primary

713-745-0394

Farhad Ravandi-Kashani

Role: primary

713-745-0394

Farhad Ravandi-Kashani

Role: primary

713-745-0394

Farhad Ravandi-Kashani

Role: primary

713-745-0394

Farhad Ravandi-Kashani

Role: primary

713-745-0394

References

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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.

Reference Type DERIVED
PMID: 39584789 (View on PubMed)

Related Links

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http://www.mdanderson.org

M D Anderson Cancer Center

Other Identifiers

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NCI-2011-02767

Identifier Type: REGISTRY

Identifier Source: secondary_id

2010-0981

Identifier Type: OTHER

Identifier Source: secondary_id

2010-0981

Identifier Type: -

Identifier Source: org_study_id