Clinical Trials

Epratuzumab and Combination Chemotherapy in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia

Location:

Trial status:

Inactive

Why is this study being done?

OBJECTIVES:

Primary

- Determine the feasibility of epratuzumab administered alone and in combination with re-induction combination chemotherapy in pediatric patients with relapsed CD22-positive acute lymphoblastic leukemia.

- Determine the toxic effects of this regimen in these patients.

- Determine the antitumor activity of this regimen in these patients.

Secondary

- Determine the pharmacokinetics of epratuzumab in these patients.

- Determine the biologic activity of epratuzumab using measurements of minimal residual disease in these patients.

- Determine the human anti-human antibody (HAHA) response in patients treated with this regimen.

OUTLINE: This is a multicenter study comprising a feasibility part A (closed to accrual as of 10/30/06) followed by a pilot part B study. Patients enrolled in part B are stratified according to relapse (first early marrow relapse occurring < 36 months from initial diagnosis vs first late marrow relapse occurring ≥ 36 months from initial diagnosis vs in second or subsequent relapse).

- Part A (closed to accrual as of 10/30/06):

- Reduction therapy: Patients receive epratuzumab IV over 1 hour on days -14, -10, -6, and -2 and cytarabine intrathecally (IT) on day -14*.

NOTE: *Patients who receive IT chemotherapy within 7 days of study entry as prior maintenance chemotherapy (e.g., before the diagnosis of relapse) will not receive this first dose of IT cytarabine.

- Re-induction therapy (block 1): Patients receive vincristine IV on days 1, 8, 15, and 22; oral prednisone two or three times daily on days 1-29; pegaspargase intramuscularly (IM) on days 2, 9, 16, and 23; dexrazoxane IV followed by doxorubicin IV over 15 minutes on day 1; methotrexate IT on days 15 and 29 for CNS-negative disease; and epratuzumab IV over 1 hour on days 8, 15, 22, and 29. Patients with CNS-positive disease also receive triple IT therapy (ITT) consisting of methotrexate, cytarabine, hydrocortisone on days -10, -6, 1 and 15.

- Re-induction therapy (block 2): Beginning at least 7 days after the last dose of IT chemotherapy, patients receive etoposide IV over 2 hours and cyclophosphamide IV over 30 minutes on days 1-5. Patients also receive high-dose methotrexate IV continuously over 24 hours on day 22. Beginning 42 hours after the start of the methotrexate infusion (day 24), patients receive leucovorin calcium IV every 6 hours for a minimum of 3 doses. Patients with CNS-negative disease also receive methotrexate IT on days 1 and 22. Patients with CNS-positive disease will receive triple IT as in re-induction therapy (block 1) on days 1 and 22. Patients receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 6 and continuing until blood counts recover.

- Re-induction therapy (part 3): Beginning at least 7 days after the last dose of IT chemotherapy, patients receive cytarabine IV over 3 hours twice daily on days 1, 2, 8, and 9 and asparaginase IM on days 2 and 9. Patients receive G-CSF SC once daily beginning on day 10 and continuing until blood counts recover.

- Part B:

- Re-induction therapy (block 1): Patients receive vincristine, prednisone, pegaspargase, doxorubicin, cytarabine, methotrexate, and epratuzumab as in phase I re-induction therapy (block 1). Patients with CNS-negative disease receive methotrexate IT on days 1 and 22. Patients with CNS-positive disease receive triple IT therapy comprising methotrexate, cytarabine, and hydrocortisone on days 8, 15, 22, and 29.

- Re-induction therapy (blocks 2 and 3): Patients receive re-induction therapy blocks 2 and 3 as in the part A re-induction therapy (blocks 2 and 3) portion of the study.

Patients are followed annually.

PROJECTED ACCRUAL: A total of 116 patients will be accrued for this study.

Who is eligible to participate?

DISEASE CHARACTERISTICS:

- Diagnosis of B-cell precursor acute lymphoblastic leukemia (ALL)

- At least 25% expression of CD22 by immunophenotyping

- In marrow relapse (M3 bone marrow) with or without associated extramedullary disease as defined by 1 of the following:

- In first or later marrow relapse occurring any time after initial diagnosis (part A [closed to accrual as of 10/30/06] or B)

- In first, early marrow relapse with or without associated extramedullary disease occurring < 36 months from the time of initial diagnosis (part B only)

- No B-cell L3 morphology OR evidence of MYC translocation by molecular or cytogenetic analysis

- No Down syndrome

- Patients with CNS or other extramedullary site involvement are allowed

PATIENT CHARACTERISTICS:

Age

- 2 to 31 years old

Performance status

- Karnofsky 50-100% (for patients > 10 years of age)

- Lansky 50-100% (for patients ≤ 10 years of age)

Life expectancy

- Not specified

Hematopoietic

- WBC ≤ 50,000/mm^3 (part A only [closed to accrual as of 10/30/06])

Hepatic

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- ALT ≤ 5 times ULN ( unless disease-related)

- Albumin ≥ 2 g/dL

Renal

- Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min OR

- Creatinine as defined by age as follows:

- ≤ 0.5 mg/dL (for patients < 1 year old)

- ≤ 0.8 mg/dL (for patients 1 to 5 years old)

- ≤ 1.0 mg/dL (for patients 6 to 10 years old)

- ≤ 1.2 mg/dL (for patients 11 to 15 years old)

- ≤ 1.5 mg/dL (for patients > 15 years old)

Cardiovascular

- Shortening fraction ≥ 27% by echocardiogram OR

- Ejection fraction ≥ 45% by MUGA

Pulmonary

- No dyspnea at rest

- No exercise intolerance

- Pulse oximetry > 94%

Other

- No active or uncontrolled infection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Recovered from prior immunotherapy

- At least 4 months since prior stem cell transplantation or rescue AND no evidence of active graft-vs-host disease

- At least 7 days since prior hematopoietic growth factors

- At least 7 days since prior biologic therapy*

- No other concurrent immunotherapy

- No other concurrent biologic therapy NOTE: *A longer washout period may be required for agents with known adverse events that occur beyond 7 days after administration

Chemotherapy

- Recovered from prior chemotherapy

- No waiting period for children who relapse while receiving standard ALL maintenance therapy

- No prior cumulative anthracycline exposure > 400 mg/m^2*

- No concurrent chemotherapy NOTE: *Each 10 mg/m2 of idarubicin should be calculated as the isotoxic equivalent of 30 mg/m2 of daunorubicin or doxorubicin

Endocrine therapy

- Not specified

Radiotherapy

- Recovered from prior radiotherapy

- No concurrent radiotherapy

Surgery

- Not specified

Other

- At least 2 days since prior hydroxyurea

- No other concurrent investigational drugs

- No other concurrent anticancer agents

Last updated: 08/03/2012

NCT ID:

NCT00098839