Comparison of Two Combination Chemotherapy Regimens in Treating Adults With Previously Untreated Leukemia or Lymphoma



Status:Completed
Conditions:Blood Cancer, Lymphoma, Leukemia
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - 120
Updated:4/21/2016
Start Date:March 1996
End Date:September 2011

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A Phase III Trial Comparing ARA-C/High-Dose Mitoxantrone ("ALL-2') to A Standard Vincristine/Prednisone Based Regimen ('L-20') as Induction Therapy For Adult Patients With Acute Lymphoblastic Leukemia (ALL): The ALL-4 Protocol

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die. Combining more than one drug may kill more tumor cells. It is
not yet known which regimen of combination chemotherapy is more effective for acute
lymphoblastic leukemia, lymphoblastic lymphoma, or chronic myelogenous leukemia.

PURPOSE: This randomized phase III trial is studying two different chemotherapy regimens and
comparing them to see how well they work in treating adults with acute lymphoblastic
leukemia, lymphoblastic lymphoma, or chronic myelogenous leukemia.

OBJECTIVES:

- Compare the incidence of complete remission (CR) following induction with the ALL-2
regimen (cytarabine and high-dose mitoxantrone) vs the L-20 regimen (vincristine and
prednisone) in previously untreated adult patients with acute lymphoblastic leukemia
(ALL), lymphoblastic lymphoma, and lymphoid blast crisis chronic myelogenous leukemia.

- Compare the time to CR, length of hospital stay, efficacy of treatment in Philadelphia
chromosome-positive ALL, and the proportion of patients achieving durable (greater than
5 years) remission in each treatment regimen.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
participating institution and antecedent lymphoid blast crisis of chronic myelogenous
leukemia (yes vs no). Patients are randomized to one of two treatment arms.

Arm I:

- Patients receive induction therapy consisting of cytarabine IV over 3 hours on days 1-5
with high-dose mitoxantrone IV on day 3 and methotrexate intrathecally on days 2 and 4.
Patients receive sargramostim (GM-CSF) subcutaneously or IV over 4 hours beginning on
day 7 and continuing until blood counts recover.

- At 7-14 days following induction therapy, patients receive consolidation therapy
consisting of vincristine IV on days 1, 8, 15, 22, and 29, oral prednisone 2-3 times
daily on days 1-30 and methotrexate intrathecally on days 8, 15, 22, and 29.

- At 2-3 weeks following the last dose of vincristine, patients receive an additional
course of consolidation therapy consisting of cyclophosphamide IV on day 1 and GM-CSF
subcutaneously beginning on day 3 and continuing until blood counts recover.

- At 3-4 weeks following the second consolidation course, patients receive a third course
of consolidation therapy consisting of cytarabine IV bolus on day 1 followed by
continuous infusion cytarabine on days 1-4 with etoposide IV over 1 hour on days 1-3
and methotrexate intrathecally on days 2 and 4. Patients receive GM-CSF subcutaneously
beginning on day 6 and continuing until blood counts recover.

- Following recovery from the third consolidation course, patients receive a fourth
consolidation course consisting of pegaspargase IV or intramuscularly (IM) on day 1.

- Following recovery from consolidation therapy patients receive 2 sequences of
maintenance therapy with sequence one consisting of vincristine IV on days 1 and 8,
oral prednisone 2-3 times daily on days 1-8, doxorubicin IV on day 15, oral
mercaptopurine 2-3 times daily on days 36-64, oral methotrexate on days 39, 46, 53, and
60, dactinomycin IV on day 85, and methotrexate intrathecally on days 36 and 43.

- At 2 weeks following sequence one of maintenance therapy, patients receive sequence two
consisting of the same regimen as in the first sequence with the addition of
cyclophosphamide IV and carmustine IV on day 15.

- Patients with CNS involvement receive whole brain radiotherapy in addition to
chemotherapy regimens.

Arm II:

- Patients receive induction therapy consisting of vincristine IV on days 1, 8, 15, 22,
and 29, oral prednisone 2-3 times daily on days 1-29, cyclophosphamide IV on day 5,
doxorubicin IV on days 23-25 and 42, methotrexate intrathecally on days 3, 5, 13, 16,
32, and 34 and GM-CSF subcutaneously or IV over 4 hours beginning from days 7 and 27
and continuing until blood counts recover.

- At approximately 3 weeks following induction therapy, patients receive consolidation
therapy consisting of cytarabine IV bolus on day 1 followed by continuous infusion
cytarabine on days 1-5, with daunorubicin IV on days 1-3 and methotrexate intrathecally
on days 2 and 4. Patients receive GM-CSF subcutaneously beginning on day 7 and
continuing until blood counts recover.

- At 6-8 weeks following the first course of consolidation therapy, patients receive a
second consolidation course consisting of cytarabine IV bolus on day 1 followed by
continuous infusion cytarabine on days 1-4 with methotrexate IV on days 1-4 and
methotrexate intrathecally on days 2 and 4. Patients receive GM-CSF subcutaneously
beginning on day 6 and continuing until blood counts recover.

- At 6-8 weeks following the second course of consolidation therapy, patients receive a
third consolidation course consisting of pegaspargase IV or IM on day 1.

- At 3-4 weeks following the third course of consolidation therapy, patients receive a
fourth consolidation course consisting of cyclophosphamide IV on day 1.

- At 3 weeks following the completion of consolidation therapy, patients receive the same
maintenance regimen as in Arm I.

Treatment continues in patients achieving complete response. Patients in both arms receive
alternating sequences of maintenance therapy over 2 years.

DISEASE CHARACTERISTICS:

- Diagnosis of one of the following malignancies:

- Acute lymphoblastic leukemia (ALL) of B- or T-cell lineage

- Philadelphia chromosome-positive ALL eligible

- Lymphoblastic lymphoma

- Chronic myelogenous leukemia in lymphoid blast crisis

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- Karnofsky 20-100%

Life expectancy:

- Not specified

Hematopoietic:

- Not specified

Hepatic:

- Bilirubin no greater than 2.0 mg/dL

- Glucocorticoids for higher bilirubin allowed prior to entry, at principal
investigator's discretion

Renal:

- Creatinine no greater than 2.0 mg/dL

- Glucocorticoids or renal radiotherapy for higher creatinine allowed prior to entry,
at principal investigator's discretion

Cardiovascular:

- Left ventricular ejection fraction at least 50%

Other:

- Not pregnant

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No prior biologic therapy

Chemotherapy

- No prior chemotherapy

Endocrine therapy

- No prior endocrine therapy

Radiotherapy

- No prior radiotherapy

Surgery

- No prior surgery
We found this trial at
7
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2010 E 90th St
Cleveland, Ohio 44195
(866) 223-8100
Cleveland Clinic Taussig Cancer Center At Taussig Cancer Institute, more than 250 highly skilled doctors,...
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125 Science Dr
Durham, North Carolina 27710
888.275.3853
Duke Comprehensive Cancer Center Leading-edge cancer care and research have been a hallmark of Duke...
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10833 Le Conte Avenue # 8-950
Los Angeles, California 90095
(310) 825-5268
Jonsson Comprehensive Cancer Center at UCLA In the late 1960s, a group of scientists and...
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Los Angeles, CA
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40 Sunshine Cottage Road
Valhalla, New York 10595
(914) 594-4000
New York Medical College The College was founded in 1860 by a group of New...
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1365 Clifton Rd NE
Atlanta, Georgia 30322
(404) 778-1900
Winship Cancer Institute at Emory University Winship Cancer Institute of Emory University is Georgia
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Atlanta, GA
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1275 York Ave
New York, New York 10021
(212) 639-2000
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
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