Know Cancer

or
forgot password

A Feasibility Pilot and Phase 2 Study Of Chemoimmunotherapy With Epratuzumab (IND #12034) for Children With Relapsed CD22-Positive Acute Lymphoblastic Leukemia (ALL)


Phase 2
2 Years
31 Years
Not Enrolling
Both
Recurrent Childhood Acute Lymphoblastic Leukemia

Thank you

Trial Information

A Feasibility Pilot and Phase 2 Study Of Chemoimmunotherapy With Epratuzumab (IND #12034) for Children With Relapsed CD22-Positive Acute Lymphoblastic Leukemia (ALL)


PRIMARY OBJECTIVES:

I. 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.

II. Determine the toxic effects of this regimen in these patients. III. Determine the
antitumor activity of this regimen in these patients.

SECONDARY OBJECTIVES:

I. Determine the pharmacokinetics of epratuzumab in these patients. II. Determine the
biologic activity of epratuzumab using measurements of minimal residual disease in these
patients.

III. 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 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.


Inclusion Criteria:



- 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

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

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

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

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

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

- Albumin ≥ 2 g/dL

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

- 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)

- Shortening fraction ≥ 27% by echocardiogram

- Ejection fraction ≥ 45% by MUGA

- No dyspnea at rest

- No exercise intolerance

- Pulse oximetry > 94%

- No active or uncontrolled infection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- 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

- 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

- Recovered from prior radiotherapy

- No concurrent radiotherapy

- At least 2 days since prior hydroxyurea

- No other concurrent investigational drugs

- No other concurrent anticancer agents

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Feasibility of an intensive chemoimmunotherapy approach for the treatment of relapsed CD-22 positive B-precursor acute lymphoblastic leukemia

Outcome Time Frame:

14 days

Safety Issue:

No

Principal Investigator

Elizabeth Raetz

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

ADVL04P2

NCT ID:

NCT00098839

Start Date:

February 2005

Completion Date:

Related Keywords:

  • Recurrent Childhood Acute Lymphoblastic Leukemia
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma

Name

Location

Baylor College of MedicineHouston, Texas  77030
Johns Hopkins UniversityBaltimore, Maryland  21205
Mayo ClinicRochester, Minnesota  55905
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Medical University of South CarolinaCharleston, South Carolina  29425-0721
Midwest Children's Cancer CenterMilwaukee, Wisconsin  53226
Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
Loma Linda University Medical CenterLoma Linda, California  92354
Newark Beth Israel Medical CenterNewark, New Jersey  07112
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
Eastern Maine Medical CenterBangor, Maine  04401
Children's Hospital Los AngelesLos Angeles, California  90027-0700
Children's National Medical CenterWashington, District of Columbia  20010-2970
Children's Hospital Central CaliforniaMadera, California  93638-8762
Primary Children's Medical CenterSalt Lake City, Utah  84113-1100
University of New Mexico Cancer CenterAlbuquerque, New Mexico  87131-5636
Nationwide Children's HospitalColumbus, Ohio  43205-2696
University of Alabama at BirminghamBirmingham, Alabama  35294-3300
University of RochesterRochester, New York  14642
Wayne State UniversityDetroit, Michigan  48202
Indiana University Medical CenterIndianapolis, Indiana  46202
University of KentuckyLexington, Kentucky  40536-0098
Oregon Health and Science UniversityPortland, Oregon  97201
Tulane University Health Sciences CenterNew Orleans, Louisiana  70112
David Geffen School of Medicine at UCLALos Angeles, California  90095
M D Anderson Cancer CenterHouston, Texas  77030
Seattle Children's HospitalSeattle, Washington  98105
Kaiser Permanente-OaklandOakland, California  94611
New York University Langone Medical CenterNew York, New York  10016
Columbia University Medical CenterNew York, New York  10032
University of Minnesota Medical Center-FairviewMinneapolis, Minnesota  55455
C S Mott Children's HospitalAnn Arbor, Michigan  48109
UMDNJ - Robert Wood Johnson University HospitalNew Brunswick, New Jersey  08903
Miller Children's HospitalLong Beach, California  90806
Childrens Hospital of Orange CountyOrange, California  92868-3874
Saint Joseph Children's Hospital of TampaTampa, Florida  33607
Children's Healthcare of Atlanta - EglestonAtlanta, Georgia  30322
The Childrens Mercy HospitalKansas City, Missouri  64108
Children's Hospital ColoradoAurora, Colorado  80045
Lucile Packard Children's Hospital Stanford UniversityPalo Alto, California  94304
University of California San Francisco Medical Center-ParnassusSan Francisco, California  94143