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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00002704
First received: November 1, 1999
Last updated: January 31, 2013
Last verified: November 2007
  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.


Condition Intervention Phase
Leukemia
Biological: filgrastim
Drug: asparaginase
Drug: cyclophosphamide
Drug: daunorubicin hydrochloride
Drug: dexamethasone
Drug: etoposide
Drug: leucovorin calcium
Drug: liposomal cytarabine
Drug: mercaptopurine
Drug: mesna
Drug: methotrexate
Drug: therapeutic hydrocortisone
Drug: thiotepa
Drug: vincristine sulfate
Radiation: low-LET electron therapy
Radiation: low-LET photon therapy
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: TREATMENT OF ISOLATED CNS RELAPSE OF ACUTE LYMPHOBLASTIC LEUKEMIA -- A PEDIATRIC ONCOLOGY GROUP-WIDE PHASE II STUDY

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Enrollment: 156
Study Start Date: January 1996
Primary Completion Date: June 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
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 Intrathecal Therapy. ARA-C/ASP/CTX/MP/MTX/VP-16; with CF; plus TIT. 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. 2-Drug Combination Chemotherapy Alternating with 2-Drug Combination Chemotherapy. MP/MTX; alternating with CTX/VCR.
Biological: filgrastim Drug: asparaginase Drug: cyclophosphamide Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: etoposide Drug: leucovorin calcium Drug: liposomal cytarabine Drug: mercaptopurine Drug: mesna Drug: methotrexate Drug: therapeutic hydrocortisone Drug: thiotepa Drug: vincristine sulfate Radiation: low-LET electron therapy Radiation: low-LET photon therapy

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002704

  Show 70 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Julio C. Barredo, MD Medical University of South Carolina
  More Information

Additional Information:
Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00002704     History of Changes
Other Study ID Numbers: NCI-2012-01528, POG-9412, CDR0000064509
Study First Received: November 1, 1999
Last Updated: January 31, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
recurrent childhood acute lymphoblastic leukemia
T-cell childhood acute lymphoblastic leukemia
B-cell childhood acute lymphoblastic leukemia
TdT positive childhood acute lymphoblastic leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
6-Mercaptopurine
Cytarabine
Methotrexate
Cyclophosphamide
Thiotepa
Asparaginase
Daunorubicin
Dexamethasone
Etoposide
Vincristine
BB 1101
Lenograstim
Dexamethasone acetate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Cortisol succinate
Hydrocortisone
Dexamethasone 21-phosphate
Hydrocortisone-17-butyrate
Leucovorin
Levoleucovorin

ClinicalTrials.gov processed this record on August 26, 2014