Combination Chemotherapy With or Without Filgrastim and/or Tretinoin in Treating Patients With Acute Myeloid Leukemia

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00005863
First received: June 2, 2000
Last updated: December 18, 2013
Last verified: January 2006
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. It is not yet known whether combination chemotherapy with filgrastim and/or tretinoin is more effective than combination chemotherapy alone for acute myeloid leukemia.

PURPOSE: This randomized phase III trial is studying combination chemotherapy with filgrastim and/or tretinoin to see how well they work compared to combination chemotherapy alone in treating patients with acute myeloid leukemia.


Condition Intervention Phase
Leukemia
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Biological: filgrastim
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: etoposide
Drug: fludarabine phosphate
Drug: tretinoin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: Protocol for Patients With High Risk (Resistant, Refractory, Relapsed or Adverse Cytogenetic) AML

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: August 1998
Study Completion Date: December 2004
Detailed Description:

OBJECTIVES:

  • Compare standard induction chemotherapy with cytarabine, daunorubicin, and etoposide vs fludarabine and cytarabine in terms of achievement of remission, reasons for remission failure, duration of remission, survival, toxicity, and supportive care needs in patients with high risk acute myeloid leukemia.
  • Determine if the use of filgrastim (G-CSF) or tretinoin administered during and following chemotherapy improves outcome in this patient population.
  • Determine the impact of these treatment regimens on quality of life in these patients.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to type of disease (resistant vs refractory vs relapsed vs adverse cytogenetic), age (under 15 vs 15 to 29, vs 30 to 49 vs 50-59 vs 60-69 vs 70 and over), performance status, and de novo and secondary leukemia. Patients with relapsed disease are further stratified according to duration of first remission (less than 6 months vs 6 to 12 months vs 12 months and over), and prior transplantation (yes vs no).

Patients are randomized into one of two treatment arms for induction chemotherapy.

  • Arm I: Patients receive induction chemotherapy consisting of cytarabine IV every 12 hours on days 1-10, daunorubicin IV on days 1, 3, and 5 and etoposide IV over 1 hour on days 1-5. Patients receive a second course of therapy with cytarabine IV every 12 hours on days 1-8 and daunorubicin and etoposide as in course 1.
  • Arm II: Patients receive 2 courses of induction chemotherapy consisting of fludarabine IV over 30 minutes followed by cytarabine IV over 4 hours on days 1-5.

Patients are further randomized into one of two treatment arms for colony stimulating factor therapy.

  • Arm I: Patients receive filgrastim (G-CSF) subcutaneously or IV daily beginning on day 1 of each course of induction chemotherapy and continuing until blood counts recover, for up to a maximum of 28 days.
  • Arm II: Patients receive no G-CSF during and following induction chemotherapy. Patients are further randomized into one of two treatment arms for retinoid therapy.
  • Arm I: Patients receive oral tretinoin daily beginning on day 1 of induction chemotherapy and continuing for up to a maximum of 90 days.
  • Arm II: Patients receive no retinoid therapy during and following induction chemotherapy.

Following completion of induction chemotherapy, patients achieving complete remission and blood count recovery may receive subsequent therapy consisting of consolidation chemotherapy and/or autologous or allogeneic transplantation.

Quality of life is assessed at 3 months.

PROJECTED ACCRUAL: Approximately 800-1,000 patients will be accrued for this study within 4-5 years.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of acute myeloid leukemia (AML) including de novo or secondary AML, or a preexisting myelodysplastic syndrome

    • Overt resistant disease with more than 15% bone marrow blasts after induction course
    • Primary refractory disease

      • Failure to achieve first complete remission after at least 2 induction courses
    • Relapse from first remission with more than 5% bone marrow blasts
    • Complete or partial remission following 1 induction course with adverse cytogenetic abnormalities at diagnosis
  • No acute promyelocytic leukemia
  • No chronic myeloid leukemia in blast transformation
  • No prior relapse from a second or greater remission

PATIENT CHARACTERISTICS:

Age:

  • Any age

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

  • Not specified

Renal:

  • Creatinine clearance at least 30 mL/min

Other:

  • No other active malignancy
  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • See Disease Characteristics

Endocrine therapy

  • Not specified

Radiotherapy

  • Not specified

Surgery

  • Not specified
  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: NCT00005863

Locations
United Kingdom
Birmingham Heartlands Hospital
Birmingham, England, United Kingdom, B9 5SS
Sponsors and Collaborators
Medical Research Council
Investigators
Study Chair: D. W. Milligan, MD Birmingham Heartlands Hospital
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00005863     History of Changes
Other Study ID Numbers: CDR0000067895, MRC-LEUK-AML-HR, EU-20008
Study First Received: June 2, 2000
Last Updated: December 18, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
adult acute erythroid leukemia (M6)
childhood acute erythroleukemia (M6)
recurrent childhood acute myeloid leukemia
recurrent adult acute myeloid leukemia
adult acute myeloid leukemia in remission
childhood acute myeloid leukemia in remission
adult acute myeloblastic leukemia without maturation (M1)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myelomonocytic leukemia (M4)
adult acute monoblastic leukemia (M5a)
adult acute megakaryoblastic leukemia (M7)
childhood acute myeloblastic leukemia without maturation (M1)
childhood acute myeloblastic leukemia with maturation (M2)
childhood acute myelomonocytic leukemia (M4)
childhood acute monoblastic leukemia (M5a)
childhood acute monocytic leukemia (M5b)
childhood acute megakaryocytic leukemia (M7)
secondary acute myeloid leukemia
de novo myelodysplastic syndromes
adult acute monocytic leukemia (M5b)
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
adult acute minimally differentiated myeloid leukemia (M0)
childhood acute minimally differentiated myeloid leukemia (M0)
atypical chronic myeloid leukemia, BCR-ABL1 negative
myelodysplastic/myeloproliferative neoplasm, unclassifiable
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)

Additional relevant MeSH terms:
Leukemia, Myeloid
Neoplasms
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Leukemia
Syndrome
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Disease
Pathologic Processes
Fludarabine
Fludarabine phosphate
Daunorubicin
Tretinoin
Lenograstim
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents

ClinicalTrials.gov processed this record on September 18, 2014