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SWOG S0333 - "A Phase II Study of Double Induction Chemotherapy for Newly Diagnosed Non-L3 Adult Acute Lymphoblastic Leukemia with Investigation of Minimal Residual Disease and Risk of Relapse Following Maintenance Chemotherapy"
Treatment Plan (Supplied Drug: None)
1st REGISTRATION - FIRST INDUCTION CHEMO*#
Allopurinol: 300mg/d, PO, Days 1-7
Daunorubicin: 60mg/m2/d, IV, Days 1, 2 & 3
Vincristine: 1.4mg/m2/d (2.0mg max), IV, Days 1, 8, 15 & 22
Prednisone: 60mg/m2/d, PO or IV, Days 1-35 (full dose through Day 28, then tapered to zero from Days 29-35)
PEG L-asparaginase: 2000 IU/m2, IM or IV, Day 15 (except pancreatitis pts)
Bactrim: 1 DS tab, PO, BID (2x/wk), until Prednisone has been discontinued
Day 28 - BM Aspir/Bx
Pts w/A1 marrow will complete Prednisone tapering through Day 35, and may be eligible for Second Induction Chemo upon achieving B1 perip blood status.
2nd REGISTRATION - SECOND INDUCTION CHEMO*#
Allopurinol: 300mg, PO, Days 1-7
Ara-C: 3g/m2, IV over 3 hrs, Days 1-5
Dexamethasone: 0.1%, QID, eye drops, Days 1-6
G-CSF: 5µg//kg/d, SC or IV, Day 7 (until granulocytes >1500/µl x 2 consecutive days)
Mitoxantrone: 80mg/m2, IV, Day 3
Day 28 - BM Aspir/Bx
Pts w/A1 marrow are eligible for Consolidation Chemo upon achieving B1 perip blood status. Pts w/resistant disease will be removed from protocol tx.
3rd REGISTRATION - CONSOLIDATION CHEMO
Cyclophosphamide: 650mg/m2, IV, Days 1, 15 & 29
Ara-C: 75mg/m2/d, IV push, Days 2-5 & 16-19
6-Mercaptopurine: 60mg/m2, PO, Days 1-28
Methotrexate: 12mg, Intrathecally or Intraventricularly, Days 2, 9, 16 & 23
G-CSF: 5µg/kg/d (as needed to maintain neutrophils >1000)
POST-CONSOLIDATION THERAPY MAINTENANCE THERAPY
Course 1
6-Mercaptopurine: 60mg/m2/day, PO, Days 1-63
Methotrexate: 20mg/m2/wk, PO, Days 1, 8, 15, 22, 29, 36, 43, 50 & 57
Course 2 (when WBC recovers to >3000/µl after Course 1)
Vincristine: 1.5mg/m2 (2.0mg max), IV, Days 1, 8, 15 & 22
Adriamycin: 25mg/m2, IV, Days 1, 8, 15 & 22
Dexamethasone: 10mg/m2/day, PO, Days 1-28
Course 3 (when WBC recovers to >3000/µl after Course 2)
Cyclophosphamide: 650mg/m2, IV, Day 1
6-Thioguanine: 60mg/m2/day, PO, Days 1-14
Ara-C: 75mg/m2/day, IV push, Days 3-6 & 10-13
Course 4 (when WBC recovers to >3000/µl after Course 3)
6-Mercaptopurine: 60mg/m2/day, PO, QD x 2 yrs
Methotrexate: 20mg/m2, PO, q week x 2 yrs
* Pts w/CNS leukemia will receive methotrexate & leucovorin calcium in addition to induction chemo.
# See protocol re: pts found to have t(9:22) or a variant or to express the p190 or p210 transcript for BCR/ABL.
Eligibility
1st REGISTRATION
Morphologically-confirmed ALL w/FAB class L1-2 or mixed lineage ALL based on blood and marrow studies w/i 14 days pre-regist. No FAB class L3, NH lymphoma, CML in lymphoid blast crisis, mixed lineage AML, or M0 AML.
No pts known to have Ph+ or BCR/ABL+ ALL. If cytogenetic data is unknown at regist and it would be detrimental to delay therapy initiation, the pt may be enrolled w/the understanding that if they are found to be Ph+, they will be deemed unevaluable from time Ph+ status is confirmed.
Age >18 & <65.
Zubrod 0-3.
No prior remission induction chemo for ALL. Hydroxyurea to control WBC count is allowed.
Serum creat <1.5x IULN or CrCl (estim or meas) >60 cc/min, or both (w/i 14 days pre-regist).
Normal LVF w/ejection fraction >50% by MUGA or 2D echo w/i 42 days pre-regist. (Use same scan throughout tx).
No symptomatic CHF, CAD, cardiomyopathy, or uncontrolled arrhythmias. Either echo or MUGA w/ejection fraction >50% w/i 28 days pre-regist. Use same method throughout tx. If pt has s/s of ischemia or CHF after cardiac eval, a repeat study must be obtained pre-regist.
No known chronic liver disease or hx of Hep B or C. Hep A pts are not excluded. If abnormal LFTs >5x IULN, must have negative hepatitis serology pre-regist.
No other prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical cancer, adequately treated Stg I or II cancer currently in complete remission, or any other cancer disease-free >5 yrs.
Must be registered to SWOG 9007, the Cytogenetics study. Pre-tx BM specimens must be collected w/i 14 days pre-regist and submitted to an approved SWOG Cytogenetics lab for analysis (may use CMH). In addition, pre-tx BM samples (preferred) or blood (only if aspirate is a dry tap) should be submitted to the SWOG FISH lab at: City of Hope National Medical Ctr (Lab #31). NOTE: Protocol also requires submission of remission, follow-up, & relapse specimens.
Must be registered on SWOG S9910, the Centralized Reference Laboratories & Tissue Repositories protocol. Pre-tx marrow &/or perip blood must be submitted to Lab #93 (SWOG ALL/CLL/CML Repository - Fred Hutchinson Cancer Research Center). Specimens will be stored in the repository only if pt consents to that optional storage. In addition, pre-tx flow cytometry specimens of marrow and perip blood must be submitted to the Wood Flow Cytometry Lab. Specimens must be collected w/i 14 days pre-regist. NOTE: Protocol also requires submission of remission, follow-up, & relapse specimens.
No pregnant or nursing women. Men/Women of reproductive potential must use effective contraception.
PRESTUDY REQUIREMENTS:
H&P, wt, PS
CBC/diff/platelets
Serum creat &/or CrCl
Total bili*
SGOT or SGPT*
Hepatitis panel (including Hep C)*
HSV, CMV titer*
HIV*
BM aspir/bx
Marrow/Blood specimens**
Lumbar puncture (for CSF cell count, cytology diff, & sugar protein)
MUGA or Echo
EKG/CXR*
* For good medical practice; results do not determine eligibility.
** For cytogenetic studies see SWOG 9007. For surface marker studies see SWOG S9910. For PCR & FISH studies, submit 1 Wright-stained perip smear, 1 Wright-Giemsa stained BM aspir smear, 5 unstained smears, and slides from the BM aspir/bx.
Signed informed consent.
SEE PROTOCOL FOR 2nd, 3rd, & 4th REGISTRATION ELIGIBILITY REQUIREMENTS.