Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia (AML-19)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2012 by European Organisation for Research and Treatment of Cancer - EORTC.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Gruppo Italiano Malattie EMatologiche dell'Adulto
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00091234
First received: September 7, 2004
Last updated: July 23, 2012
Last verified: July 2012
  Purpose

RATIONALE: Monoclonal antibodies such as gemtuzumab ozogamicin can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known whether gemtuzumab ozogamicin is more effective than standard supportive care in treating older patients who have acute myeloid leukemia.

PURPOSE: This randomized phase II/III trial is studying two different gemtuzumab ozogamicin regimens to see how well they work compared to standard supportive care in treating older patients with previously untreated acute myeloid leukemia.


Condition Intervention Phase
Leukemia
Drug: gemtuzumab ozogamicin
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Gemtuzumab Ozogamicin (GO) Monotherapy Versus Standard Supportive Care for Previously Untreated AML in Elderly Patients Who Are Not Eligible for Intensive Chemotherapy: A Randomized Phase II/III Trial (AML-19) of the EORTC-LG and GIMEMA-ALWP

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Proportion of patients able to start continuation therapy (Phase II) [ Designated as safety issue: No ]
  • Overall survival (Phase III)

Secondary Outcome Measures:
  • Rate of complete remission (CR+CRp)by the end of continuation therapy, for patients in the GO arms (Phase II) [ Designated as safety issue: No ]
  • Overall survival (Phase II) [ Designated as safety issue: No ]
  • Toxicity (CTCAE grading), including time to hematological recovery (Phase II & III) [ Designated as safety issue: No ]
  • Rate of complete remisison (CR+CRp) by the end of induction and by the end of continuation therapy, for patients in GO arm (Phase III) [ Designated as safety issue: Yes ]
  • Disease-free survival for patients who reached CR or CRp (Phase III)
  • Progression-free survival from randomization for patients in GO arm (Phase III)

Estimated Enrollment: 279
Study Start Date: June 2004
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Compare the feasibility, toxicity, and antileukemic activity of two different dosing regimens of gemtuzumab ozogamicin (GO) vs standard supportive care in older patients with previously untreated acute myeloid leukemia who are not candidates for intensive chemotherapy. (phase II)
  • Compare the efficacy and toxicity of the best dosing regimen of GO selected from phase II vs standard supportive care, in terms of overall survival, in these patients. (phase III)

OUTLINE: This is a randomized, open-label, multicenter phase II study followed by a phase III study. Patients are stratified according to age (61 to 75 vs 76 to 80 vs 81 and over), CD33-positivity of bone marrow blasts (< 20% vs 20-80% vs > 80% vs unknown), initial WBC before hydroxyurea administration (< 30,000/mm^3 vs ≥ 30,000/mm^3), WHO performance status (0-1 vs 2 vs 3-4), and participating center.

  • Phase II: Patients are randomized to 1 of 3 treatment arms.

    • Arm I: Patients receive gemtuzumab ozogamicin (GO) IV over 2 hours on days 1 and 8. Patients with stable or responding disease at day 36 receive GO IV over 2 hours every 4 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.
    • Arm II: Patients receive GO IV over 2 hours on days 1, 3, and 5. Patients with stable or responding disease at day 36 receive GO IV over 2 hours every 4 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.
    • Arm III: Patients receive standard supportive care.
  • Phase III: Patients are randomized to 1 of 2 treatment arms.

    • Arm I: Patients receive the selected treatment (arm I or arm II) from phase II.
    • Arm II: Patients receive standard supportive care. Patients who receive GO treatment are followed monthly for 1 year and then every 3 months thereafter. Patients who receive standard supportive care are followed at least every 4 weeks.

PROJECTED ACCRUAL: A total of 259 patients (75 for phase II [25 per treatment arm] and 184 for phase III [92 per treatment arm]) will be accrued for this study within 2.5 years.

  Eligibility

Ages Eligible for Study:   61 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed acute myeloid leukemia (AML)

    • At least 20% bone marrow blasts by bone marrow aspiration or biopsy
    • All subtypes except M3 (acute promyelocytic leukemia) are allowed
  • Previously untreated primary or secondary disease (including AML after myelodysplastic syndromes)
  • Ineligible for intensive chemotherapy, as defined by 1 of the following criteria:

    • 61 to 75 years old AND WHO performance status > 2 AND/OR unwilling to receive intensive chemotherapy
    • Over 75 years old
  • No blast crisis of chronic myeloid leukemia
  • No AML supervention after other myeloproliferative disease
  • WBC < 30,000/mm^3 and meets 1 of the following criteria:

    • WBC < 30,000/mm^3 at diagnosis AND had no prior treatment with hydroxyurea
    • WBC ≥ 30,000/mm^3 at diagnosis AND received mandatory pretreatment with hydroxyurea (up to 14 days duration) until WBC < 30,000/mm^3
  • No active CNS leukemia

PATIENT CHARACTERISTICS:

Age

  • See Disease Characteristics
  • 61 and over

Performance status

  • See Disease Characteristics

Life expectancy

  • Not specified

Hematopoietic

  • See Disease Characteristics

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)

Renal

  • Creatinine ≤ 1.5 times ULN

Cardiovascular

  • No arrhythmia requiring chronic treatment
  • No congestive heart failure
  • No symptomatic ischemic heart disease
  • No other severe cardiovascular disease

Pulmonary

  • No severe pulmonary dysfunction ≥ grade 3

Other

  • No alcohol abuse
  • No severe neurological or psychiatric disease
  • No active uncontrolled infection or severe systemic infection
  • No other malignancy
  • No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up
  • HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)
  • No concurrent antiangiogenic drugs

Chemotherapy

  • See Disease Characteristics
  • Concurrent low-dose cytostatic agents (i.e., thioguanine or mercaptopurine) allowed for palliative care (standard supportive care arm only)

Endocrine therapy

  • Prior corticosteroids (duration ≤ 14 days ) for primary or secondary AML allowed

Radiotherapy

  • Not specified

Surgery

  • Not specified

Other

  • No other concurrent cytotoxic drugs
  • No other concurrent experimental therapy
  • No concurrent tyrosine kinase inhibitors
  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: NCT00091234

Contacts
Contact: Hilde Breyssens hilde.breyssens@eortc.be

  Show 45 Study Locations
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Gruppo Italiano Malattie EMatologiche dell'Adulto
Investigators
Principal Investigator: Sergio Amadori, MD EORTC - AZIENDA OSPEDALLERA UNIVERSITARIA - POLICLINICO TOR VERGATA, IT
Principal Investigator: Giuliana Alimena GIMEMA - Universita Degli Studi "La Sapeinza"
  More Information

Additional Information:
Publications:
Amadori S, Suciu S, Selleslag D, et al.: Phase II-III study of gemtuzumab ozogamicin monotherapy versus best supportive care in older patients with newly diagnosed AML unfit for intensive chemotherapy: first results of the EORTC-GIMEMA AML-19 trial. [Abstract] Blood 112 (11): A-762, 2008.

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00091234     History of Changes
Other Study ID Numbers: EORTC-06031, EORTC-06031
Study First Received: September 7, 2004
Last Updated: July 23, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Belgium: Federal Agency for Medicinal Products and Health Products
Italy: Ethics Committee

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
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)
untreated adult acute myeloid leukemia
secondary acute myeloid leukemia
adult acute basophilic leukemia
adult acute eosinophilic leukemia
adult erythroleukemia (M6a)
adult pure erythroid leukemia (M6b)
adult acute megakaryoblastic leukemia (M7)
adult acute minimally differentiated myeloid leukemia (M0)
adult acute monoblastic leukemia (M5a)
adult acute monocytic leukemia (M5b)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myelomonocytic leukemia (M4)

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Gemtuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 14, 2014