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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


Phase 3
18 Years
N/A
Not Enrolling
Both
Leukemia, Lymphoma

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Trial Information

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


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.

Inclusion Criteria


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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

complete remission (CR)

Outcome Time Frame:

2 years

Safety Issue:

No

Principal Investigator

Nicole Lamanna, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

96-015

NCT ID:

NCT00002766

Start Date:

March 1996

Completion Date:

September 2011

Related Keywords:

  • Leukemia
  • Lymphoma
  • blastic phase chronic myelogenous leukemia
  • untreated adult acute lymphoblastic leukemia
  • chronic myelogenous leukemia, BCR-ABL1 positive
  • T-cell adult acute lymphoblastic leukemia
  • B-cell adult acute lymphoblastic leukemia
  • stage I adult lymphoblastic lymphoma
  • stage II adult lymphoblastic lymphoma
  • stage III adult lymphoblastic lymphoma
  • stage IV adult lymphoblastic lymphoma
  • contiguous stage II adult lymphoblastic lymphoma
  • noncontiguous stage II adult lymphoblastic lymphoma
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Lymphoma

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
Jonsson Comprehensive Cancer Center, UCLALos Angeles, California  90095-1781
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
New York Medical CollegeValhalla, New York  10595
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
Stanford Cancer Center at Stanford University Medical CenterStanford, California  94305
Winship Cancer Institute of Emory UniversityAtlanta, Georgia  30322