Know Cancer

forgot password

A Collaborative Trial for the Treatment of Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplasia

Phase 3
21 Years
Not Enrolling
Leukemia, Myelocytic, Acute

Thank you

Trial Information

A Collaborative Trial for the Treatment of Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplasia

The study compares the effectiveness of two doses of cytarabine combined with set doses of
daunomycin and etoposide as an initial course of chemotherapy to eliminate minimal residual
disease. Subsequent therapy is tailored according to cytogenetic risk features, assessments
of minimal residual disease, and availability of a suitable donor for bone marrow
transplant. Patients with higher risk disease features are given more intense therapy. For
higher risk groups, transplant is given to patients with suitable donors.

Secondary objectives include:

- To assess the prognostic value of biological markers in childhood Acute Myeloid
leukemia (AML).

- To compare the amounts of leukemia cells in the blood and bone marrow to study minimal
residual disease(MRD).

- To relate non-invasive cardiac evaluation with health-related quality of life in AML
patients treated with cardiotoxic therapy during and following therapy.

Detailed Description of Treatment Plan Induction I Patients will be randomly assigned to
receive induction therapy that consists of daunomycin, etoposide, and high-dose or low-dose

High-Dose Cytarabine (HDAC) arm:

Cytarabine 3 gm/m2 IV days 1, 3, 5 Daunomycin 50 mg/m2 IV days 2, 4, 6 Etoposide 100 mg/m2
IV days 2-6

Low-Dose Cytarabine(LDAC) arm:

Cytarabine 100 mg/m2 IV days 1-10 (20 doses) Daunomycin 50 mg/m2 IV days 2, 4, 6 Etoposide
100 mg/m2 IV days 2-6

Induction II

Patients who have < 1% MRD after Induction I will receive daunomycin, cytarabine, etoposide

Daunomycin 50 mg/m2 IV days 1, 3, 5 Cytarabine 100 mg/m2 IV 1-8 (16 doses) Etoposide 100
mg/m2 IV days 1-5

Patients who have ≥ 1% MRD after Induction I will receive daunomycin, cytarabine, etoposide
(ADE) + gemtuzumab ozogamicin:

Daunomycin 50 mg/m2 IV days 1, 3, 5 Cytarabine 100 mg/m2IV days 1-8 (16 doses) Etoposide:
100 mg/m2 IV on days 1-5 Gemtuzumab ozogamicin (GO) 3 mg/m2 IV on day 1.

Consolidation I (Chemotherapy course 3)

The chemotherapy administered in course 3 will be based on the participant's response and
cytogenetic/morphologic subgroup

MRD+ patients (except those who received ADE + GO) Gemtuzumab ozogamicin 6 mg/m2 IV on day 1

MRD+ patients who had No response(NR) to induction I

These patients should proceed to Stem Cell Transplant (SCT) as soon as possible. In cases
where SCT is delayed (e.g., during searches for unrelated donors), these patients should
receive chemotherapy according to their cytogenetic or morphologic subtype until the time of

MRD- patients (i.e., patients who were MRD- after ADE or after GO) will receive risk-based
intensification (RBI)

t(9;11) and inv(16) Cytarabine 500 mg/m2/day by continuous infusion for 120 hours Cladribine
(2CDA) 9 mg/m2: IV over 30 minutes daily for 5 days

Amend 8 M4/M5 without t(9;11) or inv(16): CE Cytarabine 3 gm/m2 IV q12h x 6 doses (days
1-3) by continuous infusion for 3 hours. Etoposide 125 mg/m2 IV on days 2-5 by continuous
infusion for at least one hour

t(8;21) and others: HAM Cytarabine 3 g/m2 IV x 6 doses (days 1-3) Mitoxantrone 10 mg/m2 IV
days 3-4

Standard-risk patients with matched related donors and high-risk patients will proceed to
stem cell transplant per institutional practice

Consolidation II (Chemotherapy course 4):

Cytarabine 3 gm/m2 IV q12 hours on days 1, 2, 8, 9 (8 doses) L-Asparaginase 6000 Units/m2 IM
3 hours after 4th and 8th doses of cytarabine

Consolidation III (Chemotherapy course 5) Mitoxantrone 10 mg/m2 IV days 1-3 Cytarabine 1
gm/m2 IV over 2 hours q12 hours on days 1-3 (6 doses)

Patients who are in first remission are eligible to be enrolled on the St. Jude protocols
NKAML protocol and receive Natural Killer (NK) cell therapy instead of Consolidation III or
after Consolidation III. At the discretion of their primary physician, these patients will
be offered the option of enrolling on NKAML.

Some patients with biphenotypic leukemia respond poorly to AML-directed therapy, but respond
quite well to lymphoid-directed therapy. Patients with such markers who have no response to
induction I or who fail to achieve complete response (CR) after induction II will therefore
receive lymphoid directed induction therapy. Other biphenotypic patients will continue to
receive AML-directed therapy as described above

All patients will undergo lumbar puncture and receive an age-appropriate dose of intrathecal
(IT) cytarabine at the time of diagnosis.

Patients without Central Nervous System disease (CNS)(i.e., less than 5 leukocytes per
microliter of CSF (colony-stimulating factor) will receive one dose of intrathecal (IT)
methotrexate, hydrocortisone, and cytarabine (MHA) with each course of chemotherapy
beginning with induction II.

Patients with overt CNS leukemia (more or equal to 5 leukocytes per l microliter of CSF and
the presence of leukemic blast cells on CSF cytospin) will receive weekly IT MHA therapy
beginning 1 week after the initial dose of IT cytarabine and continuing until the CSF is
free of blast cells (minimum number of doses, 4). These patients will then receive 4
additional doses of intrathecal therapy with methotrexate, hydrocortisone, and cytarabine
(IT MHA) (minimum total number of doses, 8) at approximately 1-month intervals (generally
given with each subsequent course of chemotherapy).

Inclusion Criteria:

- Diagnosis of acute myeloid leukemia by immunophenotyping, morphology, and
cytochemical staining; myelodysplasia; or biphenotypic leukemia.

- Age less than or equal to 21 years at time of study entry.

- No prior therapy for this malignancy (patients with secondary AML following treatment
of primary malignancy are eligible) except for one dose of intrathecal therapy.

- Negative pregnancy test

- Patient does not have Down syndrome, acute promyelocytic leukemia (APL), or juvenile
myelomonocytic leukemia (JMML)

Exclusion Criteria:

- Positive pregnancy test

- Down syndrome, acute promyelocytic leukemia (APL), or juvenile myelomonocytic
leukemia (JMML)

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Minimal Residual Disease (MRD).

Outcome Description:

Detection of Minimal Residual Disease following one course of chemotherapy where positive MRD was defined as one or more leukemic cell per 1000 mononuclear bone-marrow cells (>=0.1%).

Outcome Time Frame:

Day 22 MRD measurement

Safety Issue:


Principal Investigator

Jeffrey Rubnitz, M.D., PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

St. Jude Children's Research Hospital


United States: Institutional Review Board

Study ID:




Start Date:

August 2002

Completion Date:

June 2012

Related Keywords:

  • Leukemia, Myelocytic, Acute
  • Leukemia,Erythroblastic, Acute
  • Erythroblastic Leukemia, Acute
  • Leukemia, Myeloid, Acute
  • Myeloid Leukemia, Acute
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia



MD Anderson Cancer Center Houston, Texas  77030-4096
Stanford University Medical Center Stanford, California  94305-5408
Dana-Farber Cancer Institute Boston, Massachusetts  02115
St. Jude Children's Research Hospital Memphis, Tennessee  38105-2794
Texas Children's Cancer Center Houston, Texas  77030-2399
Seattle Children's Hospital Seattle, Washington  98105
Children's Hospital of Michigan (Wayne State University) Detroit, Michigan  48201
Cook Children's Medical Center Fort Worth, Texas  76104