- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00187083
A Study of Children With Refractory or Relapsed ALL
A Study of Children With Refractory or Relapsed Acute Lymphoblastic Leukemia (ALLR16)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The present protocol will compare the biologic effects of PEG-asparaginase vs native-forms of asparaginase in a randomized trial using the same dosages and schedules used in the POG 9411 study. Comprehensive studies, including the measurement of antibodies and asparagine levels as well as the pharmacokinetics of L-asparaginase, will be performed. This protocol will also study the changes in topoisomerase I and topoisomerase II levels and the fractions of topoisomerase I/II translocations in malignant lymphoblasts after upfront window topotecan therapy, and correlate oncolytic response with these changes.
Secondary objectives include:
- To compare changes in asparagine levels 28 days after initiation of treatment with asparaginase between the two groups.
- To estimate the pharmacokinetics of L-asparaginase, compare the pharmacokinetics between the two groups of patients, and correlate the pharmacokinetics with the development of antibody to asparaginase and depletion of asparagine.
- To measure the pharmacokinetics and pharmacodynamics of topotecan in patients with recurrent acute lymphoblastic leukemia
- To determine whether the frequency of recombinogenesis in lymphocytes is increased during or after etoposide therapy relative to the pre-therapy level, and to explore whether etoposide pharmacokinetics are related to the Day 7 or post-therapy level of recombinogenesis.
Detailed Description of Treatment Plan
WINDOW Topotecan 2.4 mg/m2 ; IV over 30 min in 5 doses Days 1-5
STANDARD INDUCTION Dexamethasone 6 mg/m2/day orally Days 8-35 Vincristine 1.5 mg/m2 (max 2.0 mg) days 8, 15, 22, 29
RANDOMIZE E. coli asparaginase 10,000 U/m2/day IM (or Erwinia if previous allergy to E. coli) Days 8, 11, 13, 15, 18, 20, 22, 25, 27, 29, 32, 34
OR
PEG-Asparaginase 2500 U/m2/day IM Days 8, 15, 22, 29
ITHMA Days 8, 22, 36
CONSOLIDATION
Fludarabine: 15 mg/m2 IV over 30 min; days 1,2,3,4 Ara-C: 2 g/m2 IV days 1,2,3,4
Patients who achieve remission on R16 induction or consolidation may be eligible for either a matched sibling or a fully matched/one-antigen-mismatched unrelated donor transplant
For patients not undergoing bone marrow transplant:
SECONDARY CONSOLIDATION
VP 16: 50 mg/m2 PO qd for 14 days. Vincristine: 1.5 mg/m2 (max 2.0 mg) IV; days 1, 8. IT MHA day 1
CONTINUATION CHEMOTHERAPY
Cycle 1:
Cyclophosphamide 1 g/m2 IV on days 1 and 2 Vincristine 1.5 mg/m2 IV on day 1 (max 2.0 mg)
Cycle 2:
VP-16 50 mg/m2 day PO daily x 14 days Decadron 6 mg/m2 PO daily ) TID x 14 days Vincristine 1.5 mg/m2 IV (max 2 mg) on days 1 and 8.
Cycle 3:
HD MTX 5 gm/m2 continuous infusion over 24 hrs E. coli Asparaginase 10,000 U/m2/dose IM qod x3 or PEG Asparaginase 2500 U/m2/dose IM x 1 (maintain same randomization for Asparaginase preparation as during induction)
Cycle 4:
High Dose Ara-C 2 g/m2/dose IV over 2 hrs q 12 hrs x 3 doses.[Total dose 6 gm/m2] Idarubicin 12 mg/m2 IV over 30 min X 1 [after completion of first dose of Ara-C] IT MHA on day 1 prior to the HDARA-C (dose of ITMHA is age adjusted as outlined in section 7.3)
STANDARD CONTINUATION CHEMOTHERAPY
Patients will receive 4-week rotational cycles of chemotherapy with the following pairs of drugs for total treatment duration of 17 months.
Week #1 Cyclophosphamide (300 mg/m2 IV) + VCR (1.5 mg/m2 IV; max 2 mg). Week #2 VM26 (200 mg/m2 IV) + Ara C (300 mg/m2 IV). Week #3 MTX (MTX should be given IM or as a 2 hr IV infusion if the patient has had previous cranial iradiation) (40 mg/m2 IV/IM) + 6 MP (75 mg/m2 PO q HS x 7) Week #4 MTX (MTX should be given IM or as a 2 hr IV infusion if the patient has had previous cranial irradiation)(40 mg/m2 IV/IM) + 6 MP (75 mg/m2 PO q HS x 7)
IT MHA: Given every 8 weeks throughout standard continuation chemotherapy for patients with CNS 1 status Given every 4 weeks for patients with CNS 2/3 status who will receive CSI at the end of chemotherapy
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
Tennessee
-
Memphis, Tennessee, United States, 38105
- St. Jude Children's Research Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria
For patients treated on frontline protocols at St. Jude:
- ALL in isolated bone marrow relapse, or combined marrow and extramedullary relapse, during or after treatment with multi-agent chemotherapy (TOTAL XI, XII, XIIIA, XIIIB), or isolated extramedullary relapse after treatment on TOTXII.
- Patients with recurrent T-Cell non-Hodgkin's lymphoma who relapse in the bone marrow with >25% blasts
For patients not treated on front-line St. Jude protocols:
• ALL in isolated bone marrow relapse, or isolated extramedullary relapse, or combined marrow and extramedullary relapse.
All patients:
- First relapse after receiving primary therapy or during primary therapy
- Life expectance of at least 8 weeks
- ECOG score 0-2 Exclusion criteria
- Life expectancy < 8 weeks
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 1
Native asparaginase
|
See Detailed Description section for details of treatment interventions.
See Detailed Description section for details of treatment interventions.
See Detailed Description section for details of treatment interventions.
See Detailed Description section for details of treatment interventions.
See Detailed Description section for details of treatment interventions.
See Detailed Description section for details of treatment interventions.
|
Experimental: 2
PEG-asparaginase
|
See Detailed Description section for details of treatment interventions.
See Detailed Description section for details of treatment interventions.
See Detailed Description section for details of treatment interventions.
See Detailed Description section for details of treatment interventions.
See Detailed Description section for details of treatment interventions.
See Detailed Description section for details of treatment interventions.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
To compare in a randomized trial the depletion of asparagine in patients who receive the native form of asparaginase or PEG-asparaginase during induction therapy.
Time Frame: December 2003
|
December 2003
|
Collaborators and Investigators
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Leukemia
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Lymphoid
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Dermatologic Agents
- Antibiotics, Antineoplastic
- Reproductive Control Agents
- Topoisomerase I Inhibitors
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Dexamethasone
- Etoposide
- Fludarabine
- Methotrexate
- Vincristine
- Asparaginase
- Idarubicin
- Topotecan
- Mercaptopurine
- Pegaspargase
- Teniposide
Other Study ID Numbers
- ALLR16
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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