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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Completed	under 18	NCI	CCG-181P

Objectives

I.  Compare "cure-oriented" therapies for ALL/AUL patients who develop first 
bone marrow relapse while receiving chemotherapy on front-line studies of 
varying intensity.
II.  Evaluate induction rates using "standard" combination chemotherapy with 
VPL (vincristine/prednisone/L-asparaginase) in patients relapsing off 
front-line studies of varying intensity.
III.  Evaluate high-dose cytosine arabinoside/L-asparaginase as reinduction 
therapy for those who fail standard VPL reinduction.
IV.  Compare allogeneic marrow transplantation following a preparative regimen 
of high-dose cytosine arabinoside/total-body irradiation to intensive 
maintenance chemotherapy with 
cyclocytidine/adriamycin/L-ASP/prednisone/vincristine/methotrexate without 
marrow transplantation (cytosine arabinoside substituted for cyclocytidine, 
per Addendum 5, May 1986).
V.  Evaluate the role of initial relapse patterns (bone marrow alone vs. bone 
marrow plus other sites) in long-term survival.
VI.  Evaluate the role of cellular phenotypes (morphologic and immunologic) as 
prognostic factors in relapsed patients.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

See General Eligibility Criteria

General Eligibility Criteria:

Children with acute lymphoblastic 
leukemia who have developed bone marrow relapse while on therapy on the 
following CCG protocols:  101, 141, 141A, 143, 905, 161, 161P, 162P, 162, 
163P, 163, 162A, 104, 105, 106, 107, 123, 192, and 193P.  Patients who relapse 
from any of these protocols while off chemotherapy for more than 3 months are 
excluded.  Patients who have a CNS or extramedullary relapse at the time of 
bone marrow relapse or a history of extramedullary relapse are eligible.  
Marrow must be classed as M3.  A life expectancy of at least 4 weeks is 
required.  Patients who have been successfully reinduced elsewhere on a 
differing regimen and who then are referred to a CCG-181P participating 
transplant institution may be entered on study for the transplant only, but 
will be followed separately.  To be eligible for allogeneic bone marrow 
transplant, patients must have a sibling donor who is an identical HLA/DR/MLC 
match or is mismatched for only one A or B locus antigen and is free of 
significant illness.  Patients must be free of significant functional defects 
in major organs and must be free of significant infection.  It is anticipated 
that some institutions will elect to transplant patients with incompatible 
donors either utilizing treated autologous marrow or T-depleted donor marrow; 
these patients will remain on study, but will be evaluated separately.

Expected Enrollment

157 patients will be entered.  With an anticipated accrual rate of 4 patients 
per month, accrual is expected to be completed within 3.25 years.  A follow-up 
period of 2.5 years is anticipated.

Outline

Nonrandomized study.  All patients receive Induction; those who do not achieve 
an M1 marrow receive Salvage Therapy.  Patients who achieve an M1 marrow 
receive Maintenance/Intensification on Regimens A or B, depending on the 
availability of an HLA/DR/MLC-matched sibling.  Patients with CNS disease at 
entry receive additional therapy on Regimen C.  Patients with testicular 
involvement at entry receive additional therapy on Regimen D; patients with 
CNS relapse without bone marrow relapse while on or off Maintenance therapy 
are treated on Regimen E.
Induction.  3-Drug Combination Chemotherapy plus Intrathecal Therapy.  VPL:  
Vincristine, VCR, NSC-67574; Prednisone, PRED, NSC-10023; E. coli 
L-Asparaginase, L-ASP, NSC-109229 (or, in the case of allergic reaction, 
Erwinia L-ASP, NSC-106977); plus intrathecal Methotrexate, MTX, NSC-740.
Salvage Therapy.  2-Drug Combination Chemotherapy.  Cytosine arabinoside, 
ARA-C, NSC-63878; L-ASP.
Maintenance/Intensification.  Regimen A:  6-Drug Combination Chemotherapy plus 
Intrathecal Therapy with (if indicated) Leukovorin Rescue.  Cyclocytidine, 
CYC, NSC-145668 (per Addendum 5, May 1986, ARA-C is now substituted for CYC); 
Adriamycin, ADR, NSC-123127; L-ASP; PRED; VCR; MTX; plus intrathecal MTX (or, 
if indicated, intrathecal ARA-C); with Citrovorum Factor, CF, NSC-3590.
Maintenance/Intensification.  Regimen B:  Single-agent Ablative Chemotherapy 
plus Radiotherapy plus Bone Marrow Therapy.  ARA-C; plus total-body 
irradiation (TBI) using supervoltage equipment (i.e., Co60, 4 and 6 MeV linear 
accelerators, and higher photon energies) and, in selected patients, a cranial 
boost using megavoltage equipment with a minimum energy of Co60 and a maximum 
energy of 6 MeV x-rays; plus allogeneic bone marrow transplant.
Regimen C:  Intrathecal Therapy.  Intrathecal MTX; or, if indicated, 
intrathecal ARA-C; Hydrocortisone, HC, NSC-10483.
Regimen D:  Radiotherapy.  Testicular irradiation using megavoltage equipment 
with a minimum energy of Co60 and a maximum energy of 10 MeV photons.
Regimen E:  Intrathecal Therapy plus Radiotherapy plus 2-Drug Combination 
Chemotherapy.  Intrathecal ARA-C; plus craniospinal irradiation using 
megavoltage equipment with a minimum energy of Co60 and a maximum energy of 6 
MeV x-rays; plus ARA-C; L-ASP.

Harris R, Feig S, Coccia P, et al.: ALL in second remission: a CCSG study comparing intensive maintenance chemotherapy to bone marrow transplantation. [Abstract] Proceedings of the American Society of Clinical Oncology 6: A-643, 163, 1987.

Nachman J, Sather HN, Buckley JD, et al.: Young adults 16-21 years of age at diagnosis entered on Childrens Cancer Group acute lymphoblastic leukemia and acute myeloblastic leukemia protocols. Results of treatment. Cancer 71 (10 Suppl): 3377-85, 1993.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Children's Cancer Group

Richard Harris, MD, Protocol chair		Ph: 513-636-8610; 800-344-2462 Email: richard.harris@cchmc.org