Clinical Trials /

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

NCT01409161

Description:

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.

Related Conditions:
  • Acute Promyelocytic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Tretinoin and Arsenic Trioxide With or Without Gemtuzumab Ozogamicin in Treating Patients With Previously Untreated Acute Promyelocytic Leukemia
  • Official Title: Phase II Study of Treatment of Acute Promyelocytic Leukemia (APL) With ATRA, Arsenic Trioxide and Gemtuzumab Ozogamicin (GO)

Clinical Trial IDs

  • ORG STUDY ID: 2010-0981
  • SECONDARY ID: NCI-2011-02767
  • SECONDARY ID: 2010-0981
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT01409161

Conditions

  • Acute Promyelocytic Leukemia With PML-RARA

Interventions

DrugSynonymsArms
Arsenic TrioxideArsenic (III) Oxide, Arsenic Sesquioxide, Arsenous Acid, Arsenous Acid Anhydride, Arsenous Oxide, Trisenox, White ArsenicTreatment (tretinoin, arsenic trioxide, gemtuzumab ozogamicin)
Gemtuzumab OzogamicinCalicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody, CDP-771, CMA-676, gemtuzumab, hP67.6-Calicheamicin, Mylotarg, WAY-CMA-676Treatment (tretinoin, arsenic trioxide, gemtuzumab ozogamicin)
Tretinoin2,4,6,8-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-, VitinoinTreatment (tretinoin, arsenic trioxide, gemtuzumab ozogamicin)

Purpose

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

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (tretinoin, arsenic trioxide, gemtuzumab ozogamicin)ExperimentalINDUCTION: 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.
  • Arsenic Trioxide
  • Gemtuzumab Ozogamicin
  • Tretinoin

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:10 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Monitored using a Bayesian time-to-event model.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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