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

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT01409161
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 150
• Locations: 5
• Arm: 1
• Anticipated Duration (Months): 146.4
• Patients Per Site: 30
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Promyelocytic Leukemia With PML-RARA	Drug: Arsenic Trioxide; Drug: Gemtuzumab Ozogamicin; Other: Laboratory Biomarker Analysis; Drug: Tretinoin	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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).

2. 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 Design

• Study Type: Interventional
• Anticipated Enrollment: 150 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Treatment of Acute Promyelocytic Leukemia (APL) With ATRA, Arsenic Trioxide and Gemtuzumab Ozogamicin (GO)
• Actual Study Start Date: Oct 5, 2011
• Anticipated Primary Completion Date: Dec 18, 2022
• Anticipated Study Completion Date: Dec 18, 2023

Arms and Interventions

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.

Drug: Arsenic Trioxide; Given IV; Other Names: Arsenic (III) Oxide Arsenic Sesquioxide Arsenous Acid Arsenous Acid Anhydride Arsenous Oxide Trisenox White Arsenic ; Drug: Gemtuzumab Ozogamicin; Given IV; Other Names: Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody CDP-771 CMA-676 gemtuzumab hP67.6-Calicheamicin Mylotarg WAY-CMA-676 ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Tretinoin; Given PO; Other Names: 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

Outcome Measures

Primary Outcome Measures

1. Event free survival [The time from the start of treatment to first documentation of disease relapse or death, assessed up to 2 years]

   Monitored using a Bayesian time-to-event model.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	M D Anderson Cancer Center	Houston	Texas	United States	77030
2	MD Anderson Regional Care Center-Katy	Houston	Texas	United States	77094
3	MD Anderson Regional Care Center-Bay Area	Nassau Bay	Texas	United States	77058
4	MD Anderson Regional Care Center-Sugar Land	Sugar Land	Texas	United States	77478
5	MD Anderson Regional Care Center-The Woodlands	The Woodlands	Texas	United States	77384

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Kiran Naqvi, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT01409161
• Other Study ID Numbers: 2010-0981; NCI-2011-02767; 2010-0981
• First Posted: Aug 4, 2011
• Last Update Posted: May 10, 2022
• Last Verified: May 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Leukemia; Leukemia, Promyelocytic, Acute; Vitamins; Vitamin A; Tretinoin; Retinol palmitate; Arsenic Trioxide; Gemtuzumab; Calicheamicins

Study Results

No Results Posted as of May 10, 2022