Chemotherapy Plus Monoclonal Antibody in Treating Patients With Acute Promyelocytic Leukemia

Phase II Study Of Combined Modality Postremission Therapy As Determined By Molecular Response (Adaptive Regulation) In The Treatment Of Acute Promyelocytic Leukemia (APL)

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining monoclonal antibody therapy with chemotherapy may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy and monoclonal antibody in treating patients who have acute promyelocytic leukemia.

Study Overview

• Status: Completed
• Conditions: Leukemia
• Intervention / Treatment: Drug: arsenic trioxide; Biological: filgrastim; Drug: idarubicin; Drug: tretinoin; Biological: lintuzumab

Detailed Description

OBJECTIVES:

• Determine the disease-free and overall survival of patients with acute promyelocytic leukemia in clinical complete remission following tretinoin-based induction therapy treated with monoclonal antibody HuG1-M195, arsenic trioxide, idarubicin, and tretinoin.
• Determine the rate of molecular complete remission in patients treated with this regimen.
• Determine the toxicity of this regimen in this patient population.
• Determine the number and length of hospitalizations of patients treated with this regimen.

OUTLINE: Patients receive monoclonal antibody HuG1-M195 (MOAB HuM195) IV over 40-60 minutes twice weekly for 3 weeks. Approximately 2-4 weeks after completion of MOAB HuM195, patients receive arsenic trioxide IV over 1-4 hours daily for a total of 25 days with no more than 5 days between doses.

Beginning approximately 4-6 weeks after completion of arsenic trioxide, patients receive idarubicin IV daily on days 1-3 or 1-4 and filgrastim (G-CSF) subcutaneously daily beginning on day 5 or 6 and continuing until blood counts recover. Treatment repeats every 4 weeks for patients who remain RT-PCR positive or are newly converted to RT-PCR negative (molecular complete remission) following a prior course of idarubicin for a maximum of 3 courses. Patients who remain RT-PCR positive following course 3 of idarubicin receive no further treatment on study.

Beginning 3 months after completion of idarubicin, patients in molecular complete remission receive oral tretinoin daily for 14 days. Treatment repeats every 3 months for a total of 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed monthly.

PROJECTED ACCRUAL: Approximately 35 patients will be accrued for this study within 2-3 years.

• Study Type: Interventional
• Enrollment (Anticipated): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Diagnosis of acute promyelocytic leukemia by positive RT-PCR assay for PML/RAR-alfa rearrangement or a t(15;17) karyotype

  • Achieved clinical complete remission within the past 1-2 months
  • Prior induction therapy must have contained tretinoin
• No other acute myeloid leukemia diagnosis

PATIENT CHARACTERISTICS:

Age:

• Any age

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin less than 2 mg/dL
• Transaminases no greater than 3 times upper limit of normal

Renal:

• Creatinine less than 2 mg/dL OR
• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• Ejection fraction normal or greater than 50% by echocardiogram or MUGA

Other:

• No other concurrent active malignancy
• No other serious or life-threatening condition that would preclude study
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 4 months after study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• At least 1 week since prior retinoids

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• No prior postremission therapy of any form

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
reverse transcriptase-polymerase chain reaction negativity

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: November 1, 2000
• Primary Completion (Actual): March 1, 2007

Study Registration Dates

• First Submitted: May 6, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): January 16, 2013
• Last Update Submitted That Met QC Criteria: January 15, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: adult acute myeloid leukemia with t(15;17)(q22;q12); childhood acute myeloid leukemia in remission; adult acute myeloid leukemia in remission; childhood acute promyelocytic leukemia (M3); adult acute promyelocytic leukemia (M3)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia; Leukemia, Promyelocytic, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Dermatologic Agents; Antibiotics, Antineoplastic; Keratolytic Agents; Arsenic Trioxide; Idarubicin; Tretinoin; Lintuzumab
• Other Study ID Numbers: 00-072; MSKCC-00072; NCI-H01-0073