Phase III Randomized Study of Dexamethasone Versus Prednisone During Induction and High-Dose Methotrexate With Leucovorin Rescue Versus Escalating-Dose Methotrexate Without Leucovorin Rescue During Interim Maintenance I in Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia.

Dexamethasone Compared With Prednisone During Induction Therapy and Methotrexate With or Without Leucovorin During Maintenance Therapy in Treating Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia

Note: this outline was patched together from the NCI online protocol and input from parents of kids with ALL. It is summarized here for our convenience, so that we can quickly compare our protocols. We do not guarantee the accuracy of this outline - it is not an official document. You can contact your child's oncologist and ask for the complete protocol document if you are interested in the details of your child's protocol.

This trial on the site.

Classification of newly diagnosed leukemia

All newly diagnosed ALL patients are enrolled in COG AALL03B1, Classification of Acute Lymphoblastic Leukemia.

At diagnosis of ALL, the oncologists at the local hospital determine an initial risk classification as follows:

(This method of risk classification is known as "NCI/Rome criteria".)

At diagnosis samples of blood/bone marrow aspirate/CFS are taken and studied for cytogenetic/immunophenotype characteristics (see later in the protocol how the results of these tests might effect the treatment.)

HR ALL is treated on AALL0232, as outlined below. SR ALL is treated on AALL0331. The protocols for infant, T-cell, and very high risk will be added to this site when they are available.


Briefly, the four arms are:

What is escalating dose methotrexate?

Escalating dose means that they start with 100 mg/m2 and raise the dose by 50 mg/m2 until toxicity is apparent, meaning that the ANC goes down or mucositis is apparent. The methotrexate is given every 10 days. This is called "Capizzi I methotrexate" and was a component of previous trials, CCG 1961 (arms C/D) and POG 9906, during interim maintenance. The augmented arms of CCG 1961 (arms C/D) proved to give the highest EFS (this information is published as abstracts on the Blood Journal web site, ASH, 2004; click on the ASH (American Society of Hematology) link on the right - ASH Annual Meeting Abstracts. Then click on the 2004 annual meeting abstracts.)

What is high dose methotrexate?

High dose methotrexate (HD MTX) is 5 grams/m2 administered by IV. Leucovorin rescue is used and begins 42 hours after MTX treatment begins and continues until the MTX is cleared. HD MTX was used successfully in BFM-style protocols in conjunction with 6-MP and is also referred to as "Protocol M".

Why dexamethasone vs prednisone?

Dexamethasone seems to work better but has serious (and potentially long-lasting) side effects, prednisone is less toxic. This study aims to find the optimum steroid dosage.

Here is a flow chart for this trial on the Grand Rapids Clinical Oncology Program web site.

Induction, 4 weeks

Arms DC and DH:

Note: Patients with CNS3 disease also receive IT MTX on days 15 and 22

Arms PC and PH:

Note: Patients with CNS3 disease also receive IT MTX on days 15 and 22

Patients in all arms are evaluated at day 29 of induction:

Extended induction therapy (only for patients with M2 disease or M1 disease with over 1% MRD):

Patients on all arms who have M1 disease and less than 1% MRD after extended induction proceed to consolidation therapy and continue as SER patients. All other patients are removed from study (and probably put on the highest risk study).


However, it looks like it is the "1%" amount that directs the path of treatment at the end of induction(s), although the positive/negative definition is included in the definitions for SER or RER, which in itself directs treatment later on.

Note: CNS 3 patients are assigned to regimen DH with double delayed intensification, 2 extra Induction ITs and craniospinal radiation.

Consolidation (about 7-8 weeks)

Arms DC, DH, PC, PH:

Note: Patients with CNS3 disease receive MTX on days 1 and 8 only.

Interim maintenance I

DC (dexamethasone, escalating-dose MTX)

DH (dexamethasone, high-dose MTX)

PC (prednisone, escalating-dose MTX) (same as DC in this phase of treatment)

PH (prednisone, high-dose MTX) (same as DH in this phase of treatment)

Delayed intensification(s)

(Note that SER patients received two delayed intensifications.)

Arms DC, DH, PC, PH:

After delayed intensification I:

Interim maintenance II

Delayed intensification II

Maintenance therapy

Maintenance therapy repeats every 12 weeks until total duration of therapy is 2 years from the start of interim maintenance I for female patients and 3 years from the start of interim maintenance I for male patients.

Patients with testicular disease may receive testicular radiotherapy for 8 days during one of the first 3 courses of maintenance therapy.

Patients are followed every 2 months for 2 years, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

and this: RER : Randomize and receive SDI
SER : Randomize, receive DDI, and cranial XRT (1200 cGy)

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Last Updated 4/06

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