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

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ClinicalTrials.gov Identifier: NCT01409161
Recruitment Status : Recruiting
First Posted : August 4, 2011
Last Update Posted : November 14, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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:

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  (Clinical Trial)
Estimated Enrollment : 150 participants
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 : October 5, 2011
Estimated Primary Completion Date : October 31, 2019
Estimated Study Completion Date : October 31, 2019


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




Primary Outcome Measures :
  1. Event free survival [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   10 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01409161


Contacts
Contact: Kiran Naqvi 713-745-5073 knaqvi@mdanderson.org

Locations
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Kiran Naqvi    713-745-5073      
Principal Investigator: Kiran Naqvi         
MD Anderson Regional Care Center-Katy Not yet recruiting
Houston, Texas, United States, 77094
Contact: Kiran Naqvi    713-745-5073      
Principal Investigator: Kiran Naqvi         
MD Anderson Regional Care Center-Bay Area Not yet recruiting
Nassau Bay, Texas, United States, 77058
Contact: Kiran Naqvi    713-745-5073      
Principal Investigator: Kiran Naqvi         
MD Anderson Regional Care Center-Sugar Land Not yet recruiting
Sugar Land, Texas, United States, 77478
Contact: Kiran Naqvi    713-745-5073      
Principal Investigator: Kiran Naqvi         
MD Anderson Regional Care Center-The Woodlands Not yet recruiting
The Woodlands, Texas, United States, 77384
Contact: Kiran Naqvi    713-745-5073      
Principal Investigator: Kiran Naqvi         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Kiran Naqvi M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01409161     History of Changes
Other Study ID Numbers: 2010-0981
NCI-2011-02767 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2010-0981 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: August 4, 2011    Key Record Dates
Last Update Posted: November 14, 2018
Last Verified: November 2018

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
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Vitamins
Vitamin A
Retinol palmitate
Arsenic trioxide
Gemtuzumab
Tretinoin
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Anticarcinogenic Agents
Antineoplastic Agents
Keratolytic Agents
Dermatologic Agents