S0535, Gemtuzumab and Combination Chemotherapy in Treating Patients With Previously Untreated Acute Promyelocytic Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00551460
First received: October 30, 2007
Last updated: July 15, 2013
Last verified: July 2013

October 30, 2007
July 15, 2013
November 2007
June 2016   (final data collection date for primary outcome measure)
  • Continuous complete remission at 3 years [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Mortality rate at 6 weeks [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Continuous complete remission at 3 years
  • Mortality rate at 6 weeks
Complete list of historical versions of study NCT00551460 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
S0535, Gemtuzumab and Combination Chemotherapy in Treating Patients With Previously Untreated Acute Promyelocytic Leukemia
S0535, A Phase II Study of ATRA, Arsenic Trioxide and Gemtuzumab Ozogamicin in Patients With Previously Untreated High-Risk Acute Promyelocytic Leukemia

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as gemtuzumab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Gemtuzumab may also stop the growth of promyelocytic leukemia by blocking blood flow to the cancer. Giving gemtuzumab together with combination chemotherapy may be more effective in treating promyelocytic leukemia.

PURPOSE: This phase II trial is studying how well giving gemtuzumab together with combination chemotherapy works in treating patients with previously untreated promyelocytic leukemia.

OBJECTIVES:

  • To assess the event-free survival and death during the first six weeks in patients with previously untreated, high-risk acute promyelocytic leukemia treated with a combined regimen of tretinoin, arsenic trioxide, and gemtuzumab ozogamicin.
  • To estimate the frequency and severity of toxicities of this regimen in this group of patients.
  • To investigate the molecular response rate utilizing this regimen in high-risk patients.

OUTLINE:

  • Induction chemotherapy: Patients receive oral tretinoin twice daily beginning on day 1 until CR (up to 90 days), gemtuzumab ozogamicin IV over 2 hours on day 1, and arsenic trioxide IV over 2 hours 5 days a week beginning on day 10 until CR (up to 60 days) in the absence of disease progression or unacceptable toxicity. Patients achieving A1 bone marrow, B1 peripheral blood, and C1 extramedullary disease status proceed to consolidation therapy after maintaining B1 peripheral blood status for ≥ 7 days.
  • Consolidation therapy: Beginning between 2-8 weeks after documentation of complete response (CR), patients receive consolidation therapy.

    • Consolidation courses 1 and 2: Patients receive arsenic trioxide IV over 2 hours 5 days a week for 5 weeks. Treatment repeats every 7 weeks for up to 2 courses. Patients remaining in A1 bone marrow, B1 peripheral blood, and C1 extramedullary disease status continue with consolidation courses 3 and 4.
    • Consolidation courses 3 and 4: Within 4 weeks of completing consolidation course 2, patients receive oral tretinoin twice daily on days 1-7 and daunomycin IV bolus or over 1 hour on days 1-3. Within 2-8 weeks after recovery to B1 peripheral blood status, patients receive consolidation course 4 as in course 3. Patients who remain in B1 peripheral blood and C1 extramedullary disease status continue on consolidation courses 5 and 6.
    • Consolidation courses 5 and 6: Beginning between 2-8 weeks after recovery to B1 peripheral blood status, patients receive gemtuzumab IV over 2 hours on day 1. Between 2-8 weeks after recovery to B1 peripheral blood status, patients receive consolidation course 6 as in course 5. Patients who remain in A1 bone marrow, B1 peripheral blood, and C1 extramedullary disease status proceed to maintenance therapy.
  • Maintenance therapy: Beginning 2-8 weeks after recovery of blood counts, patients receive oral tretinoin twice daily on days 1-7 every other week for 1 year, oral mercaptopurine once daily for 1 year, and oral methotrexate once weekly for 1 year.

Patients undergo bone marrow aspirates and biopsies periodically during study. Samples are analyzed for cytogenetics by fluorescence in situ hybridization (FISH) and for PML-RARα by polymerase chain reaction (PCR).

After completion of study treatment, patients are evaluated at 3, 6, 9, 12, 18, 24, and 36 months.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Leukemia
  • Drug: arsenic trioxide
  • Drug: gemtuzumab ozogamicin
  • Drug: mercaptopurine
  • Drug: methotrexate
  • Drug: tretinoin
Experimental: Treatment

Induction:

ATRA 45mg/m2 PO D1-CR Gemtuzumab Ozogamicin 9 mg/m2 IV D1 Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk D10-CR

Consolidation 1 and 2:

Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk x 5 weeks, repeat after 2 weeks rest

Consolidation 2 and 3:

ATRA 45 mg/m2 PO D1-7 Daunomycin 50 mg/m2/d IV D1-3

Consolidation 5 and 6:

GO 9mg/m2 IV D1

Maintenance:

ATRA 45 mg/m2/d PO D1-7 every 14 days 6-MP 60 mg/m2/d PO daily for 1 year Methotrexate 20 mg/m2 PO once/wk for 1 year

Interventions:
  • Drug: arsenic trioxide
  • Drug: gemtuzumab ozogamicin
  • Drug: mercaptopurine
  • Drug: methotrexate
  • Drug: tretinoin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
70
Not Provided
June 2016   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Morphologically confirmed acute promyelocytic leukemia (APL) based on bone marrow examination

    • APL-RARα-negative by RT-PCR are not eligible
  • High-risk disease, defined as WBC > 100,000/mm^3
  • Bone marrow specimens must be made available for cytogenetic studies

PATIENT CHARACTERISTICS:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No prolonged QTc > 0.47 sec
  • No other malignancy within the past 5 years, except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or stage II cancer from which the patients is currently in complete remission

PRIOR CONCURRENT THERAPY:

  • No prior systemic chemotherapy for acute leukemia

    • At least 3 days since prior tretinoin (ATRA) allowed
  • Prior hydroxyurea, corticosteroids, or leukapheresis to control high cell counts allowed
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00551460
CDR0000572619, S0535, U10CA032102
Yes
Southwest Oncology Group
Southwest Oncology Group
National Cancer Institute (NCI)
Study Chair: Jeffrey E. Lancet, MD H. Lee Moffitt Cancer Center and Research Institute
Study Chair: Rami Komrokji, MD H. Lee Moffitt Cancer Center and Research Institute
Study Chair: Cheryl L. Willman, MD University of New Mexico Cancer Center
Study Chair: Marilyn L. Slovak, PhD Beckman Research Institute
Southwest Oncology Group
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP