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: August 19, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Leukemia
Drug: arsenic trioxide
Drug: gemtuzumab ozogamicin
Drug: mercaptopurine
Drug: methotrexate
Drug: tretinoin
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: S0535, A Phase II Study of ATRA, Arsenic Trioxide and Gemtuzumab Ozogamicin in Patients With Previously Untreated High-Risk Acute Promyelocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • 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 ]

Estimated Enrollment: 70
Study Start Date: November 2007
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Drug: arsenic trioxide Drug: gemtuzumab ozogamicin Drug: mercaptopurine Drug: methotrexate Drug: tretinoin

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00551460

  Show 192 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Investigators
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
  More Information

Additional Information:
No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00551460     History of Changes
Other Study ID Numbers: CDR0000572619, S0535, U10CA032102
Study First Received: October 30, 2007
Last Updated: August 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Southwest Oncology Group:
adult acute promyelocytic leukemia (M3)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
untreated adult acute myeloid leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Promyelocytic, Acute
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Methotrexate
Arsenic trioxide
Gemtuzumab
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on October 02, 2014