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

National Cancer Institute (NCI)

Status and phase

Completed

Phase 2

Conditions

Leukemia

Treatments

Drug: asparaginase

Drug: cyclophosphamide

Drug: methotrexate

Radiation: low-LET electron therapy

Radiation: low-LET photon therapy

Drug: mesna

Biological: filgrastim

Drug: leucovorin calcium

Drug: liposomal cytarabine

Drug: daunorubicin hydrochloride

Drug: mercaptopurine

Drug: vincristine sulfate

Drug: therapeutic hydrocortisone

Drug: thiotepa

Drug: etoposide

Drug: dexamethasone

Study type

Interventional

Funder types

NIH

Identifiers

NCT00002704

NCI-2012-01528

CDR0000064509 (Registry Identifier)

POG-9412

Details and patient eligibility

About

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.

Full 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.

Enrollment

156 patients

Sex

All

Ages

Under 20 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

156 participants in 1 patient group

Arm I

Experimental group

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 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.

Treatment: