COG-AALL01P2

Intensive Induction Therapy for Children with Acute Lymphoblastic Leukemia (ALL) who Experience a Bone Marrow Relapse

A phase II trial. Dates this clinical trial was active: 1/03 to 12/05

Online references:

• cancer.gov outline
• ASH abstract of results (2006)
• ASH abstract of results (2004; MRD article)

Comments: This protocol includes 3-35 day treatment blocks. At the end of these blocks, early vs late bone marrow relapse patients are advised as follows:

• Early Relapse (less than 36 months from initial diagnosis - sometimes this is stated as less than 36 months in first complete remission): Stem cell transplantation is recommended (preferentially HLA matched family member).
• Late Relapse (greater than 36 months from initial diagnosis): If an HLA matched family donor is available, BMT is recommended. If not, continued chemotherapy is recommended. (Not specified in the protocol.)

Other comments:

• CNS disease: Craniospinal radiation is advised but not mandatory; patients going on to transplant will receive radiation as part of the conditioning, but those not going to transplant may or may not have radiation.
• Testicular disease: Testicular radiation is administered after the 3 treatment blocks, the amount of radiation depends on whether or not a BMT will be given.
• Ph+ patients receive STI571 (Gleevec, imatinib mesylate)
• M3 bone marrow is the definition of relapse, and M3 means over 25% blasts in the marrow
• MRD is measured but does not direct treatment

All patients with bone-marrow=only relapse are randomized to arm A or B; patients with CNS disease are assigned to arm B. The differences in the arms is the sequence of the 3 blocks:

• Arm A is block 1, 2, 3
• Arm B is block 1, 3, 2

(so block 1 is induction; each is 35 days)

Note: this summary is an outline only and does not contain all the specifics about bone marrow aspirates, and how their results direct treatment, ANC levels necessary to continue therapy, and other important details.

Block 1 (induction)

Day 1: Ara C IT

Day 1: doxorubicin IV

Days 1, 8, 15, 22: vincristine IV

Days 2, 8, 15, 22: PEG-asparaginase

Days 15, 29: methotrexate IT (CNS negative patients)

Days 8, 15, 22, 29: methotrexate/ara C/hydrocortisone IT (CNS positive patients)

Days 1-29: Prednisone PO

Days 1-14: STI571 (imatinib mesylate) for Ph+ patients only

Block 2

Days 1, 22: IT therapy, methotrexate if CNS negative, methotrexate/ara C/hydrocortisone if CNS positive

Days 1-5: Etoposide IV and cyclophosphamide IV

Day 6 and beyond: GCSF as necessary to bring counts up

Day 22: high-dose methotrexate IV, with leucovorin rescue

Days 1-14: STI571 (imatinib mesylate) for Ph+ patients only

Block 3

Days 1, 2 (4 doses) and Days 8, 9 (4 doses): Ara C IV

Days 2 and 9: After last ara C dose, patients receive L-asparaginase IM

Day 10 and beyond: GCSF as necessary to bring counts up

Days 1-14: STI571 (imatinib mesylate) for Ph+ patients only