Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy in Treating Patients With Untreated Acute Lymphoblastic Leukemia

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	15 and over	NCI	CLB-19802 NCT00003700, CALGB-19802

Objectives

1. Determine the complete response rate and toxicity of escalating doses of daunorubicin in patients under 60 years old with untreated acute lymphoblastic leukemia (ALL).
2. Determine the complete response rate and toxicity of a constant dose of daunorubicin in patients at least 60 years old with untreated ALL.
3. Determine the toxicity of high dose cytarabine during postremission therapy in these patients.
4. Determine the CNS relapse rate of ALL when prophylactic intrathecal methotrexate and high-dose intravenous chemotherapy replace cranial irradiation.

Entry Criteria

Disease Characteristics:

• Histologically proven acute lymphoblastic leukemia (FAB L1 or L2) or acute undifferentiated leukemia



• Must be registered on companion protocol CALGB-9862

Prior/Concurrent Therapy:

Biologic therapy

• Prior emergency leukapheresis allowed
• No other prior biologic therapy for leukemia

Chemotherapy

• Prior emergency treatment with hydroxyurea for hyperleukocytosis allowed
• No other prior chemotherapy for leukemia
• No other concurrent chemotherapy

Endocrine therapy

• No prior endocrine therapy for leukemia
• No concurrent hormonal therapy (except steroids for adrenal failure or hormones for nondisease related conditions)

Radiotherapy

• One prior dose of cranial radiotherapy for CNS leukostasis allowed
• No other prior radiotherapy for leukemia
• No concurrent palliative radiotherapy except whole brain irradiation for CNS disease

Surgery

• Not specified

Patient Characteristics:

Age

• 15 and over

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Expected Enrollment

A total of 140 patients will be accrued for this study within 15 months.

Outline

• Course I: Patients are assigned to 1 of 2 induction treatment groups based on age.
  • Group 1 (under age 60): Patients receive cyclophosphamide IV over 15-30 minutes on day 1, escalating doses of daunorubicin IV over 5-10 minutes on days 1-3, vincristine IV on days 1, 8, 15, and 22, oral prednisone on days 1-21, asparaginase intramuscularly on days 5, 8, 11, 15, 18, and 22, and filgrastim (G-CSF) subcutaneously (SC) beginning on day 4 and continuing for at least 7 days and then until blood counts recover.
  
  
  
  • Group 2 (age 60 and over): Patients receive vincristine, asparaginase, cyclophosphamide, and G-CSF as in group 1, fixed dose daunorubicin IV over 5-10 minutes on days 1-3, and oral prednisone on days 1-7.
  
  
  

  Patients are then evaluated for bone marrow cellularity on day 29. Those with M0, M1, or M2 cellularity proceed to course II. Patients with M3 cellularity may proceed to course II or be removed from study.




• Course II (early intensification): Patients receive intrathecal methotrexate and cyclophosphamide IV over 15-30 minutes on day 1, cytarabine IV over 3 hours on days 1-3, and G-CSF SC beginning on day 4.

  Bone marrow is again examined on day 29. Patients with M0 or M1 cellularity after course I and no sign of relapse after course II proceed to course III. Patients with M2 or M3 cellularity after course I must have M0 or M1 cellularity after course II to proceed to course III. Patients with M2 or M3 cellularity after course II are removed from study.




• Course III: Patients receive intrathecal methotrexate, vincristine IV, and methotrexate IV over 3 hours on days 1, 8, and 15 and oral methotrexate every 6 hours for 4 doses beginning 6 hours after starting methotrexate IV on days 1, 2, 8, 9, 15, and 16. Patients receive leucovorin calcium IV 6 hours after the last oral methotrexate dose on days 2, 9, and 16 and oral leucovorin calcium beginning 12 hours after leucovorin calcium IV for at least 4 doses on days 3, 4, 10, 11, 17, and 18.

  Patients must be off leucovorin calcium for a minimum of 3 days before beginning days 8 and 15 of treatment. Patients who maintain M0 or M1 cellularity on day 29 of course III continue therapy. Those with M2 or M3 cellularity after course III are removed from the study.




• Course IV (Late intensification): Repeat course I.



• Course V (Late intensification): Repeat course II.



• Course VI (CNS intensification): Repeat course III.



• Course VII (Prolonged maintenance): Patients receive oral mercaptopurine daily, vincristine IV once every 4 weeks, oral prednisone on days 1-5, and oral methotrexate on days 1, 8, 15, and 22. Courses repeat every 4 weeks for up to 18 months.

Patients with testicular disease receive gonadal radiotherapy anytime after course I. Chemotherapy is not halted during radiotherapy.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually for 10 years.

Stock W, Yu D, Johnson J, et al.: Intensified Daunorubicin during induction and post-remission therapy of adult acute lymphoblastic leukemia (ALL): results of CALGB 19802. [Abstract] Blood 102 (11 Pt 1): A-1375, 2003.

Stock W, Dodge RK, Vardiman JW, et al.: Treatment of adult acute lymphoblastic leukemia (ALL): phase II trial of dose intensification of Daunorubicin and Cytarabine followed by high-dose Methotrexate and intrathecal Methotrexate in place of cranial irradiation (CALGB 19802). [Abstract] Blood 98 (11 Pt 1): A-2472, 2001.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Wendy Stock, MD, Protocol chair		Ph: 773-834-8982; 888-824-0200

Registry Information
Official Title		Phase II Study in Adults with Untreated Acute Lymphoblastic Leukemia Testing Increased Doses of Daunorubicin During Induction, and Cytarabine During Consolidation, Followed by High-Dose Methotrexate and Intrathecal Methotrexate in Place of Cranial Irradiation
Trial Start Date		1999-01-15
Registered in ClinicalTrials.gov		NCT00003700
Date Submitted to PDQ		1998-12-18
Information Last Verified		2004-08-09
NCI Grant/Contract Number		U10-CA31946

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