Birmingham, Alabama 35294

  • Leukemia

Purpose:

Phase II trial to study the effectiveness of radiation therapy following chemotherapy in treating children with CNS relapse from acute lymphoblastic leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with radiation therapy may kill more cancer cells.


Study summary:

OBJECTIVES: I. Determine the efficacy and toxicity of intensified systemic treatment with delayed central nervous system (CNS) irradiation in children with acute lymphoblastic leukemia and isolated CNS disease. II. Determine the efficacy of systemic thiotepa in reducing or clearing blasts in the cerebrospinal fluid of these patients. III. Evaluate the toxicity of single dose thiotepa followed by dexamethasone, vincristine, daunorubicin, and triple intrathecal therapy in these patients. IV. Determine the response rate of intrathecal sustained release cytarabine (DTC101) in patients with first bone marrow remission with first isolated CNS relapse. V. Assess the safety and toxicity of DTC101 in these patients. OUTLINE: Patients with significant neurologic symptoms (e.g., seizures, cranial nerve palsy, paresis, mental status changes) are entered directly on the Induction regimen and do not receive the Therapeutic Window. The following acronyms are used: ARA-C Cytarabine, NSC-63878 ASP Asparaginase, NSC-109229 (E. coli) or 106977 (Erwinia) CF Leucovorin calcium, NSC-3590 CTX Cyclophosphamide, NSC-26271 DM Dexamethasone, NSC-34521 DNR Daunorubicin, NSC-82151 DTC101 Sustained release cytarabine G-CSF Granulocyte Colony-Stimulating Factor (Amgen), NSC-614629 HC Hydrocortisone, NSC-10483 Mesna Mercaptoethane sulfonate, NSC-113891 MP Mercaptopurine, NSC-755 MTX Methotrexate, NSC-740 TIT Triple Intrathecal Therapy, IT MTX/IT HC/IT ARA-C TMP-SMX Trimethoprim-sulfamethoxazole TSPA Thiotepa, NSC-6396 VCR Vincristine, NSC-67574 VP-16 Etoposide, NSC-141540 THERAPEUTIC WINDOW: Single Agent Chemotherapy. TSPA or DTC101. ** Thiotepa window closed as of 7/6/98 ** ** DTC101 window opened 11/15/99 ** INDUCTION: 3-Drug Combination Chemotherapy plus Triple Intrathecal Therapy. DM/DNR/VCR; plus TIT. CONSOLIDATION: 2-Drug Combination Chemotherapy plus Triple Intrathecal Therapy. ARA-C/ASP; plus TIT. INTENSIFICATION I: 4-Drug Combination Chemotherapy with Leucovorin Rescue plus Triple Intrathecal Therapy. CTX/MP/MTX/VP-16; with CF; plus TIT. RE-INDUCTION: 3-Drug Combination Chemotherapy plus Triple Intrathecal Therapy. DM/DNR/VCR; plus TIT. INTENSIFICATION II: 6-Drug Combination Chemotherapy with Leucovorin Rescue plus Triple Intrathecal Therapy. ARA-C/ASP/CTX/MP/MTX/VP-16; with CF; plus TIT. CHEMORADIOTHERAPY: Radiotherapy plus 3-Drug Combination Chemotherapy. Craniospinal irradiation using x-rays with energies of 4-6 MV (electrons acceptable for spinal cord irradiation); plus ASP/DM/VCR. MAINTENANCE: 2-Drug Combination Chemotherapy Alternating with 2-Drug Combination Chemotherapy. MP/MTX; alternating with CTX/VCR.


Criteria:

DISEASE CHARACTERISTICS: - Acute lymphoblastic leukemia in first bone marrow remission (M1) with first isolated initial CNS relapse - More than 5 WBC/microliter in cerebrospinal fluid (CSF) with blasts on cytospin OR immunophenotypic proof (encouraged) of relapse in CSF - Identifiable blasts and presence on 2 CSF samples 3 weeks apart - If B-cell terminal deoxynucleotidyl transferase (TdT) OR CD-10 - If T-cell TdT alone OR with CD-7 PATIENT CHARACTERISTICS: - Age: Over 6 months and under 21 years at relapse - Patients receiving sustained release cytarabine - Performance status: Older than 10 years - Karnofsky greater than 50% Less than 10 years - Lansky greater than 50% - Platelet count greater than 40,000/mm3 - Bilirubin less than 2.0 mg/dL - SGPT less than 5 times normal - Creatinine less than 1.5 times normal for age - Normal metabolic parameters (serum electrolytes, calcium, and phosphorus) - No clinical evidence of obstructive hydrocephalus, compartmentalization of the CSF flow, ventriculoperitoneal or ventriculoatrial shunt PRIOR CONCURRENT THERAPY: - Prior cumulative anthracycline dose less than 375 mg/sqm - Patients receiving sustained release cytarabine - At least 7 days since prior investigational drug - At least 3 weeks since prior CNS directed therapy (6 weeks is prior nitrosourea) - At least 1 week since intrathecal chemotherapy - At least 8 weeks since prior craniospinal radiotherapy


Study is Available At:


Original ID:

NCI-2012-01528


NCT ID:

NCT00002704


Secondary ID:

POG-9412


Study Acronym:


Brief Title:

Radiation Therapy and Chemotherapy in Treating Children With CNS Relapse From Acute Lymphoblastic Leukemia


Official Title:

TREATMENT OF ISOLATED CNS RELAPSE OF ACUTE LYMPHOBLASTIC LEUKEMIA -- A PEDIATRIC ONCOLOGY GROUP-WIDE PHASE II STUDY


Overall Status:

Completed


Study Phase:

Phase 2


Genders:

Both


Minimum Age:

N/A


Maximum Age:

20 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

National Cancer Institute (NCI)


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Intervention Model: Single Group Assignment, Mask


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

156


Enrollment Type:

Actual


Overall Contact Information

Official Name:Julio C. Barredo, MD
Study Chair
Medical University of South Carolina

Study Dates

Start Date:January 1996
Primary Completion Date:June 2004
Primary Completion Type:Actual
Verification Date:November 2007
Last Changed Date:January 31, 2013
First Received Date:November 1, 1999

Study Outcomes

There are no available Study Outcomes

Study Interventions

Intervention Type:Biological
Name:filgrastim
Arm Name:Arm I
Intervention Type:Drug
Name:asparaginase
Arm Name:Arm I
Intervention Type:Drug
Name:cyclophosphamide
Arm Name:Arm I
Intervention Type:Drug
Name:daunorubicin hydrochloride
Arm Name:Arm I
Intervention Type:Drug
Name:dexamethasone
Arm Name:Arm I
Intervention Type:Drug
Name:etoposide
Arm Name:Arm I
Intervention Type:Drug
Name:leucovorin calcium
Arm Name:Arm I
Intervention Type:Drug
Name:liposomal cytarabine
Arm Name:Arm I
Intervention Type:Drug
Name:mercaptopurine
Arm Name:Arm I
Intervention Type:Drug
Name:mesna
Arm Name:Arm I
Intervention Type:Drug
Name:methotrexate
Arm Name:Arm I
Intervention Type:Drug
Name:therapeutic hydrocortisone
Arm Name:Arm I
Intervention Type:Drug
Name:thiotepa
Arm Name:Arm I
Intervention Type:Drug
Name:vincristine sulfate
Arm Name:Arm I
Intervention Type:Radiation
Name:low-LET electron therapy
Arm Name:Arm I
Intervention Type:Radiation
Name:low-LET photon therapy
Arm Name:Arm I

Study Arms

Study Arm Type:Experimental
Arm Name:Arm I
Description:Single Agent Chemotherapy. TSPA or DTC101. 3-Drug Combination Chemotherapy plus Triple Intrathecal Therapy. DM/DNR/VCR; plus TIT. 2-Drug Combination Chemotherapy plus Triple Intrathecal Therapy. ARA-C/ASP; plus TIT. 4-Drug Combination Chemotherapy with Leucovorin Rescue plus Triple Intrathecal Therapy. CTX/MP/MTX/VP-16; with CF; plus TIT. 3-Drug Combination Chemotherapy plus Triple Intrathecal Therapy. DM/DNR/VCR; plus TIT. 6-Drug Combination Chemotherapy with Leucovorin Rescue plus Triple Intra

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Reference
Citation:Eapen M, Zhang MJ, Devidas M, Raetz E, Barredo JC, Ritchey AK, Godder K, Grupp S, Lewis VA, Malloy K, Carroll WL, Davies SM, Camitta BM. Outcomes after HLA-matched sibling transplantation or chemotherapy in children with acute lymphoblastic leukemia in a second remission after an isolated central nervous system relapse: a collaborative study of the Children's Oncology Group and the Center for International Blood and Marrow Transplant Research. Leukemia. 2007 Nov 22; [Epub ahead of print]
PMID:18033318
Reference Type:Results Reference
Citation:Barredo JC, Devidas M, Lauer SJ, Billett A, Marymont M, Pullen J, Camitta B, Winick N, Carroll W, Ritchey AK. Isolated CNS relapse of acute lymphoblastic leukemia treated with intensive systemic chemotherapy and delayed CNS radiation: a pediatric oncology group study. J Clin Oncol. 2006 Jul 1;24(19):3142-9.
PMID:16809737

Data Source: ClinicalTrials.gov

Date Processed: September 23, 2021

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