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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00002704
• Collaborator: (none)
• Enrollment: 156
• Locations: 70
• Arm: 1
• Patients Per Site: 2.2

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	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

Detailed Description

OBJECTIVES:

1. 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.

2. Determine the efficacy of systemic thiotepa in reducing or clearing blasts in the cerebrospinal fluid of these patients.

3. Evaluate the toxicity of single dose thiotepa followed by dexamethasone, vincristine, daunorubicin, and triple intrathecal therapy in these patients.

4. Determine the response rate of intrathecal sustained release cytarabine (DTC101) in patients with first bone marrow remission with first isolated CNS relapse.

5. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 156 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: TREATMENT OF ISOLATED CNS RELAPSE OF ACUTE LYMPHOBLASTIC LEUKEMIA -- A PEDIATRIC ONCOLOGY GROUP-WIDE PHASE II STUDY
• Study Start Date: Jan 1, 1996
• Actual Primary Completion Date: Jun 1, 2004

Arms and Interventions

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 20 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama Comprehensive Cancer Center	Birmingham	Alabama	United States	35294
2	MBCCOP - University of South Alabama	Mobile	Alabama	United States	36688
3	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
4	University of California San Diego Cancer Center	La Jolla	California	United States	92093-0658
5	Lucile Packard Children's Hospital at Stanford	Palo Alto	California	United States	94304
6	University of California Davis Medical Center	Sacramento	California	United States	95817
7	Children's Hospital and Health Center	San Diego	California	United States	92123-4282
8	Yale Comprehensive Cancer Center	New Haven	Connecticut	United States	06520-8028
9	Walter Reed Army Medical Center	Washington	District of Columbia	United States	20307-5000
10	Shands Hospital and Clinics, University of Florida	Gainesville	Florida	United States	32610-100277
11	Sylvester Cancer Center, University of Miami	Miami	Florida	United States	33136
12	Miami Children's Hospital	Miami	Florida	United States	33155
13	CCOP - Florida Pediatric	Tampa	Florida	United States	33682-7757
14	Emory University Hospital - Atlanta	Atlanta	Georgia	United States	30322
15	Children's Memorial Hospital, Chicago	Chicago	Illinois	United States	60614
16	University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
17	CCOP - Wichita	Wichita	Kansas	United States	67214-3882
18	Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
19	MBCCOP - LSU Medical Center	New Orleans	Louisiana	United States	70112
20	Tulane University School of Medicine	New Orleans	Louisiana	United States	70112
21	CCOP - Ochsner	New Orleans	Louisiana	United States	70121
22	Marlene & Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland	United States	21201
23	Johns Hopkins Oncology Center	Baltimore	Maryland	United States	21287
24	Boston Floating Hospital Infants and Children	Boston	Massachusetts	United States	02111
25	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
26	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts	United States	01655
27	Children's Hospital of Michigan	Detroit	Michigan	United States	48201
28	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216-4505
29	Cardinal Glennon Children's Hospital	Saint Louis	Missouri	United States	63104
30	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
31	CCOP - Northern New Jersey	Hackensack	New Jersey	United States	07601
32	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
33	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
34	Schneider Children's Hospital	New Hyde Park	New York	United States	11042
35	Mount Sinai School of Medicine	New York	New York	United States	10029
36	University of Rochester Cancer Center	Rochester	New York	United States	14642
37	State University of New York Health Sciences Center - Stony Brook	Stony Brook	New York	United States	11790-9832
38	State University of New York - Upstate Medical University	Syracuse	New York	United States	13210
39	Memorial Mission Hospital	Asheville	North Carolina	United States	28801
40	Carolinas Medical Center	Charlotte	North Carolina	United States	28232-2861
41	Presbyterian Healthcare	Charlotte	North Carolina	United States	28233-3549
42	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
43	East Carolina University School of Medicine	Greenville	North Carolina	United States	27858-4354
44	Comprehensive Cancer Center of Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina	United States	27157-1082
45	Oklahoma Memorial Hospital	Oklahoma City	Oklahoma	United States	73126-0307
46	CCOP - Columbia River Program	Portland	Oregon	United States	97213
47	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania	United States	19134-1095
48	Rhode Island Hospital	Providence	Rhode Island	United States	02903
49	Medical University of South Carolina	Charleston	South Carolina	United States	29425-0721
50	Children's Hospital of Greenville Hospital System	Greenville	South Carolina	United States	29605
51	Saint Jude Children's Research Hospital	Memphis	Tennessee	United States	38105-2794
52	Medical City Dallas Hospital	Dallas	Texas	United States	75230
53	Simmons Cancer Center - Dallas	Dallas	Texas	United States	75235-9154
54	Baylor College of Medicine	Houston	Texas	United States	77030
55	San Antonio Military Pediatric Cancer and Blood Disorders Center	Lackland Air Force Base	Texas	United States	78236-5300
56	MBCCOP - South Texas Pediatric	San Antonio	Texas	United States	78284-7810
57	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284-7811
58	Cancer Center, University of Virginia HSC	Charlottesville	Virginia	United States	22908
59	Naval Medical Center, Portsmouth	Portsmouth	Virginia	United States	23708-2197
60	Massey Cancer Center	Richmond	Virginia	United States	23298-0037
61	West Virginia University Hospitals	Morgantown	West Virginia	United States	26506-9162
62	Midwest Children's Cancer Center	Milwaukee	Wisconsin	United States	53226
63	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
64	McMaster Division	Hamilton	Ontario	Canada	L8N 3Z5
65	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
66	Montreal Children's Hospital	Montreal	Quebec	Canada	H3H 1P3
67	Hopital Sainte Justine	Montreal	Quebec	Canada	H3T 1C5
68	University of Puerto Rico School of Medicine Medical Sciences Campus	San Juan		Puerto Rico	00936-5067
69	Swiss Pediatric Oncology Group Bern	Bern		Switzerland	CH 3010
70	Clinique de Pediatrie	Geneva		Switzerland	1211

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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; Children's Oncology Group; Center for International Blood and Marrow Transplant Research. 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. 2008 Feb;22(2):281-6. Epub 2007 Nov 22.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00002704
• Other Study ID Numbers: NCI-2012-01528; POG-9412; CDR0000064509
• First Posted: Jul 1, 2004
• Last Update Posted: Feb 1, 2013
• Last Verified: Nov 1, 2007

• 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; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leucovorin; Cytarabine; Dexamethasone; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Cyclophosphamide; Thiotepa; Methotrexate; Etoposide; Vincristine; Daunorubicin; Asparaginase; Mercaptopurine; Levoleucovorin

Study Results

No Results Posted as of Feb 1, 2013