AALL02P2

Treatment of Late Isolated Extramedullary Relapse from Acute Lymphoblastic Leukemia (ALL) (Initial CR1 ≥ 18 months)

No phase specified.

Online reverences:

• cancer.gov
• clinicaltrials.gov

This trial is for ALL (either B-precursor or T-Lineage) in first bone marrow remission with first isolated CNS and/or testicular relapse. Length of initial complete remission must be greater than 18 months from the time of initial diagnosis. Bone marrow must be M1 by morphology.

Comments:

• CNS Relapse is defined as at least 5 WBCs/microliter in the CSF with blasts present on cytospin.
• Any number of WBC in CSF with immunophenotypic proof of leukemic relapse, meaning that they test for TdT or CD-10 positive cells for B-precursor leukemia or TdT and CD-7 for T-cell leukemia
• Testicular Relapse is defined as biopsy-proven testicular involvement.
• Total anthracycline dosage before treatment on this protocol must be ≤ 360 mg/m2.

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

Comments on treatment plan:

• Common induction, consolidation, re-induction, and intensification.
• Isolated testicular relapse will start induction with a single dose of high-dose methotrexate and will not receive either testicular nor cranial radiation.
• Isolated CNS relapse will not receive the initial dose of HDMTX prior to Induction, but will receive cranial radiation after completing the initial 12 months of therapy.
• Combined testicular and CNS relapse will be treated with a mixture of the testicular and CNS therapies as described in detail in the protocol.
• Maintenance therapy differs according to the type of relapse.

Induction

(weeks 1-4)

(week -2 is when testicular/CNS treatments occur)

Days 1, 8, 15, 22: vincristine IV

Days 1-28: dexamethasone

Days 1, 8, 15: Daunorubicin

Day 1 (testicular relapse only) or Days 1, 8, 15 (CNS relapse): Triple ITs (methotrexate, hydrocortisone, ara C)

(additional treatment if CNS is not clear)

Consolidation

(weeks 5-10, unless additional treatment has occurred because of CNS disease remaining)

Days 1, 2, 22, 23: high dose Ara C (over 3 hours every 12 hours x 4 doses) (G-CSF 24 hours after last dose)

Days 1, 23: PEG asparaginase

Intensification I

(weeks 11-22, unless additional treatment has occurred because of CNS disease remaining)

Day 1 of weeks 11, 14, 17, 20: high dose methotrexate IV with leucovorin rescue

Days 2-6 of weeks 11, 14, 17, 20: 6MP PO

Day 1 of weeks 12, 15, 18, 21: etoposide IV/mesna

Day 1 of weeks 12, 15, 18, 21: Cyclophosphamide IV

Day 1 of weeks 13, 16, 19, 22 if CNS relapse or weeks 16 and 22 testicular relapse: TITs (triple ITs, mtx, hydrocortisone, ara C)

Re-induction

(weeks 23 -26, unless additional treatment has occurred because of CNS disease remaining)

The total dose of anthracyclines on this study is capped at 450 mg/m2;

Patients 13 years or older receive dexamethasone discontinuously (daily during weeks
23 and 25 only). Patients less than 13 years of age receive dexamethasone continuously for 28 days.

Days 1, 8, 15, 22: vincristine

Days 1-28 or days 1-7 and 15-21 if age greater than 13: dexamethasone

Days 1, 8, 15: daunorubicin

Intensification II

(weeks 27-50, unless additional treatment has occurred because of CNS disease remaining)

Days 1, 2 weeks 27, 33, 39, 45): HD ara C IV

Day 2 weeks 27, 33, 39, 45): PEG asparaginase

Day 22 (weeks 30, 36, 42, 48 if CNS positive, weeks 30 and 42 if testicular relapse): TITs

Day 29 weeks 31, 37, 43, 49: HD methotrexate

Days 30-34 weeks 31, 37, 43, 49: 6MP PO

Day 36 weeks 32, 38, 44, 50: etoposide IV/mesna

Day 36 weeks 32, 38, 44, 50: cyclophosphamide

Radiation and Chemotherapy

(Weeks 51-54, unless additional treatment has occurred because of CNS disease remaining)

Days 1-21 or days 1-7 and 15-21 if age greater than 13: dexamethasone

Days 1, 8, 15: vincristine

Days 1, 15: PEG asparaginase

FOR CNS RELAPSE PATIENTS ONLY. Cranial radiation of 1200 cGy (8 daily fractions of 150 cGy
each) will be delivered during this phase of therapy.

Maintenance for Isolated CNS Relapse ONLY

Weeks 55 -104

Maintenance consists of 10 week cycles x 5.

Days 1-5: dexamethasone

Days 1-42: 6MP

Days 1, 8, 15, 22, 29, 36: methotrexate IM

Days 43, 50, 57, 64: vincristine

Days 43, 50, 57, 64: cyclophosphamide

Maintenance for Isolated Testicular Relapse (ITR)

weeks 55-74 - repeat 10 week cycle twice

Day 1: TIT

Days 1-5: dexamethasone

Days 1-42: 6MP

Days 1, 8, 15, 22, 29, 36: methotrexate IM

Days 43, 50, 57, 64: vincristine

Days 43, 50, 57, 64: cyclophosphamide