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Clinical Trials (PDQ®)

Phase III Randomized Study of Extended Chemotherapy Using Non-Cross Resistant Drug Combinations vs Abbreviated Chemotherapy Followed by Autologous Bone Marrow Therapy in Children with AML

Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIITreatmentCompleted21 and underNCIPOG-8821
POG-8821/22

Objectives

I.  Determine the disease-free survival and event-free survival of previously 
untreated children with acute myelocytic leukemia (AML) treated with induction 
therapy consisting of DAT (daunomycin/cytosine arabinoside/6-thioguanine) 
followed by high-dose cytosine arabinoside and seven courses of alternating 
non-cross resistant consolidation chemotherapy consisting of 
etoposide/azacytidine followed by high-dose cytosine arabinoside followed by 
DAT.
II.  Compare the treatment outcome of patients randomized to the above 
consolidation regimen with that of patients randomized to consolidation 
consisting of one course of etoposide/azacytidine followed by autologous bone 
marrow therapy using the busulfan/cyclophosphamide preparative regimen and 
marrow purged with 4-hydroxyperoxycyclophosphamide.
III.  Correlate treatment outcome with clinical and laboratory features.

Entry Criteria

Disease Characteristics:


Previously untreated acute myelocytic leukemia (M1-M7), with
or without granulocytic sarcoma

  Previously untreated granulocytic sarcoma with normal bone
  marrow (not over 25% blasts) also eligible

CNS disease allowed

Appropriate FAB classification studies and cytochemical
stains required

Cytocentrifuge and tissue slides required for CNS disease or
isolated granulocytic sarcoma at presentation

Prior hematopoietic disease or prior malignancy allowed
(including appropriate antineoplastic therapy)


Prior/Concurrent Therapy:


Biologic therapy:
  No prior therapy for current disease

Chemotherapy:
  No prior chemotherapy for AML

  Prior cumulative anthracycline dose no more 250 mg/sqm (in
  patients with prior antineoplastic therapy for prior
  malignancy)

Endocrine therapy:
  No prior therapy for current disease

Radiotherapy:
  No prior therapy for current disease

Surgery:
  No prior therapy for current disease


Patient Characteristics:


Age:
  No more than 21

Performance status:
  Not specified

Hematopoietic:
  No extreme hyperleukocytosis (100,000 or more) requiring
  leukapheresis or exchange transfusion (study coordinator
  should be notified if there is any question)

Hepatic:
  Bilirubin less than 1.2 mg/dl

Renal:
  Creatinine less than 1.2 mg/dl
  Uric acid less than 8.0 mg/dl

Cardiovascular:
  Normal cardiac function demonstrated by MUGA or
  echocardiogram if history of prior anthracycline therapy

Other:
  No proven or suspected sepsis or significant infection


Expected Enrollment

In order to accrue the required 75 patients per randomization arm, it is 
estimated that entry of 76 patients/year will be required and that the total 
accrual period will be about 2.5 years.

Outline

All patients receive identical Induction therapy; those who achieve CR are 
randomized for Consolidation on Arms I and II (patients who are not eligible 
for the transplant arm are assigned nonrandomly to Arm I).  While allogeneic 
bone marrow transplantation is not an integral part of this protocol, this 
option is available to patients with a suitable donor should it be desired; 
the timing of allogeneic marrow transplant is the same as for autologous 
marrow transplant, and it is suggested that the preparative regimen be the 
same.  Patients undergoing allogeneic marrow transplant remain on study and 
continue to be followed for eventual outcome.
Induction:  3-Drug Combination Systemic Chemotherapy plus Single-agent 
Intrathecal Chemotherapy followed by Single-agent High-Dose Systemic 
Chemotherapy.  DAT:  Daunomycin, Daunorubicin, DNM, NSC-82151; Cytosine 
arabinoside, Cytarabine, ARA-C, NSC-63878; Thioguanine, 6-TG, NSC-752; plus 
intrathecal ARA-C; followed by High-dose ARA-C.
Consolidation.
Arm I:  Alternating Courses of Combination and Single-agent Systemic 
Chemotherapy plus Intrathecal Chemotherapy.  Etoposide, VP-16, NSC-141540; 
Azacytidine, AZC, NSC-102816; alternating with High-dose ARA-C with or without 
DNM; alternating with DAT; plus intrathecal ARA-C.
Arm II:  2-Drug Combination Systemic Chemotherapy plus Single-agent 
Intrathecal Chemotherapy followed (on POG-8822) by Marrow Ablation with 2-Drug 
Combination Chemotherapy followed by Autologous Bone Marrow Therapy.  VP-16; 
AZC; plus intrathecal ARA-C; followed by Busulfan, BU, NSC-750; 
Cyclophosphamide, CTX, NSC-26271; followed by reinfusion of autologous marrow 
treated with 4-Hydroperoxycyclophosphamide (4-HC).

Published Results

Parsons SK, Gelber S, Cole BF, et al.: Quality-adjusted survival after treatment for acute myeloid leukemia in childhood: A Q-TWiST analysis of the Pediatric Oncology Group Study 8821. J Clin Oncol 17 (7): 2144-52, 1999.[PUBMED Abstract]

Raimondi SC, Chang MN, Ravindranath Y, et al.: Chromosomal abnormalities in 478 children with acute myeloid leukemia: clinical characteristics and treatment outcome in a cooperative pediatric oncology group study-POG 8821. Blood 94 (11): 3707-16, 1999.[PUBMED Abstract]

Ravindranath Y, Yeager AM, Chang MN, et al.: Autologous bone marrow transplantation versus intensive consolidation chemotherapy for acute myeloid leukemia in childhood. Pediatric Oncology Group. N Engl J Med 334 (22): 1428-34, 1996.[PUBMED Abstract]

Ravindranath Y, Yeager A, Krischer J, et al.: Intensive consolidation chemotherapy (ICC) vs purged autologous bone marrow transplantation (ABMT) early in remission for treatment of childhood acute myeloid leukemia (AML): preliminary results of Pediatric Oncology Group (POG) study 8821. [Abstract] Proceedings of the American Society of Clinical Oncology 13: A-1053, 320, 1994.

Ravindranath Y, Abella E, Krischer J, et al.: Acute myeloid leukemia (AML) in Down syndrome (DS): response and toxicity with high dose arabinosyl cytosine (ARA-C). [Abstract] Proceedings of the American Society of Clinical Oncology 12: A-1071, 323, 1993.

Related Publications

Horan JT, Alonzo TA, Lyman GH, et al.: Impact of disease risk on efficacy of matched related bone marrow transplantation for pediatric acute myeloid leukemia: the Children's Oncology Group. J Clin Oncol 26 (35): 5797-801, 2008.[PUBMED Abstract]

Ravindranath Y, Chang M, Steuber CP, et al.: Pediatric Oncology Group (POG) studies of acute myeloid leukemia (AML): a review of four consecutive childhood AML trials conducted between 1981 and 2000. Leukemia 19 (12): 2101-16, 2005.[PUBMED Abstract]

Taub JW, Matherly LH, Stout ML, et al.: Enhanced metabolism of 1-beta-D-arabinofuranosylcytosine in Down syndrome cells: a contributing factor to the superior event free survival of Down syndrome children with acute myeloid leukemia. Blood 87 (8): 3395-403, 1996.[PUBMED Abstract]

Abella E, Katz J, Ravindranath Y, et al.: Toxicity with high dose cytarabine (ARA-C) in children: experience on Pediatric Oncology Group (POG) leukemia/lymphoma studies. [Abstract] Proceedings of the American Society of Clinical Oncology 13: A-1052, 320, 1994.

Trial Contact Information

Trial Lead Organizations

Pediatric Oncology Group

Yaddanapudi Ravindranath, MBBS, Protocol chair
Ph: 313-745-5649
Email: ravi@med.wayne.edu

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.

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