Combination Chemotherapy in Treating Children With Lymphoma

Lymphoma Clinical Trial

Official title:

A Pilot Study For The Treatment of Newly-Diagnosed Disseminated Anaplastic Large Cell Ki-1 Lymphoma and T-Large Cell Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002590
• Other study ID #: 5941
• Secondary ID: CCG-5941CDR00000
• Status: Completed
• Phase: Phase 2
• First received: November 1, 1999
• Last updated: July 23, 2014
• Start date: July 1994
• Est. completion date: March 2007

Study information

• Verified date: July 2014
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating children who have lymphoma.

Description:

OBJECTIVES: I. Estimate the toxicity and feasibility of intensifying the New York I (NYI) regimen by adding etoposide and cytarabine, increasing the dose of methotrexate, using pegaspargase, and compressing the treatment duration (11 months) in previously untreated children with disseminated anaplastic (Ki-1 positive) large cell and large cell T-cell lymphoma. II. Provide preliminary data for a future phase III study that will compare this intensified regimen with the high-risk ALL regimen NYI in children with disseminated lymphoblastic lymphoma. III. Continue to investigate the immunophenotype, cytogenetics, and molecular biology of lymphoblastic lymphoma and their relationship to leukemia. IV. Obtain preliminary data on treatment of anaplastic large cell (Ki-1) and T-cell large cell lymphoma treated with intensive NYI.

OUTLINE: Patients with CNS disease at diagnosis receive craniospinal irradiation on Regimen A at the conclusion of Maintenance chemotherapy. The following acronyms are used: ARA-C Cytarabine, NSC-63878 CF Leucovorin calcium, NSC-3590 CTX Cyclophosphamide, NSC-26271 DNR Daunorubicin, NSC-82151 DOX Doxorubicin, NSC-123127 G-CSF Granulocyte Colony-Stimulating Factor (Amgen), NSC-614629 MTX Methotrexate, NSC-740 PEG-ASP Pegaspargase, NSC-624239 PRED Prednisone, NSC-10023 TG Thioguanine, NSC-752 VCR Vincristine, NSC-67574 VP-16 Etoposide, NSC-141540 Induction: 5-Drug Combination Systemic Chemotherapy with Hematopoietic Stimulation plus 2-Drug Combination Intrathecal Chemotherapy. VCR/PRED/CTX/DNR/PEG-ASP; with G-CSF; plus IT ARA-C/IT MTX. Consolidation: 7-Drug Combination Systemic Chemotherapy with Hematopoietic Stimulation plus Single-Agent Intrathecal Chemotherapy. VCR/PRED/PEG-ASP/VP-16/TG/ARA-C/MTX/CF; with G-CSF; plus IT MTX. Maintenance: Sequential Pulses of 2-, 3-, 3-, and 2-Drug Systemic Chemotherapy Combinations plus Single-Agent Intrathecal Chemotherapy. CTX/TG/IT MTX; VCR/PRED/DOX; VCR/MTX/CF/PEG-ASP; ARA-C/VP-16. Regimen A: Radiotherapy. Craniospinal irradiation using megavoltage equipment.

PROJECTED ACCRUAL: 40 patients will be entered over approximately 10 months. If 4 or more toxic deaths occur in the first 15 patients or 5 or more toxic deaths occur in the first 30 patients, accrual will stop. As of 05/96, asparaginase has been replaced with pegaspargase; 15-25 additional patients will be accrued. As of 01/97, a maximum of 35 patients will be accrued for PEG asparaginase-containing treatment regimen. As of 5/97, this study is open only to patients with anaplastic large cell and T cell large cell lymphoma. Approximately 60-90 patients will be accrued.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 221
• Est. completion date: March 2007
• Est. primary completion date: March 2001
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 20 Years

Eligibility

DISEASE CHARACTERISTICS: Histologically confirmed and previously untreated anaplastic large cell Ki-1 lymphoma and T-cell large cell lymphoma Malignant lymphoblasts (identified by immunophenotype) in pleural fluid, ascitic fluid, or bone marrow sufficient for diagnosis Large cell lymphoma with T-cell phenotype eligible Localized mediastinal disease and bone lymphoma eligible CNS disease eligible and defined as: Any clearly identifiable tumor cells in cerebral spinal fluid Cranial nerve palsy (if not explained by extra cranial tumor) Clinical Spinal Cord Compression Isolated intra cerebral mass No cranial nerve palsies requiring immediate CNS irradiation

PATIENT CHARACTERISTICS: Age: Under 21 Performance status: Not specified Hematopoietic:

Not specified Hepatic: Not specified Renal: Not specified Cardiovascular: Shortening fraction greater than 27% on echocardiogram (ECHO) OR Left ventricular ejection fraction greater than 47% on radionuclide scan (RCNA) OR Cardiac function assessed as within normal limits by cardiologist ECHO or RCNA obtained as close as clinically possible to start of therapy

PRIOR CONCURRENT THERAPY: No prior therapy except emergency treatment of airway obstruction or superior vena cava syndrome No more than 72 hours between emergency radiotherapy or steroids and initiation of protocol therapy

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma

Intervention

Biological:
• filgrastim

Drug:
• cyclophosphamide

• cytarabine

• daunorubicin hydrochloride

• doxorubicin hydrochloride

• etoposide

• leucovorin calcium

• methotrexate

• pegaspargase

• prednisone

• thioguanine

• vincristine sulfate

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Canada	IWK Grace Health Centre	Halifax	Nova Scotia
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Children's Hospital Medical Center - Cincinnati	Cincinnati	Ohio
United States	Ireland Cancer Center	Cleveland	Ohio
United States	Children's Hospital of Columbus	Columbus	Ohio
United States	Children's Hospital of Denver	Denver	Colorado
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Long Beach Memorial Medical Center	Long Beach	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	Vanderbilt Cancer Center	Nashville	Tennessee
United States	Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Children's Hospital of Orange County	Orange	California
United States	St. Joseph's Hospital and Medical Center	Paterson	New Jersey
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Doernbecher Children's Hospital	Portland	Oregon
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	UCSF Cancer Center and Cancer Research Institute	San Francisco	California
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

References & Publications (4)

Abromowitch M, Sposto R, Perkins S, et al.: Outcome of Children's Cancer Group (CCG) 5941: a pilot study for the treatment of newly diagnosed pediatric patients with disseminated lymphoblastic lymphoma. [Abstract] Proceedings of the American Society of Cl

Abromowitch M, Sposto R, Perkins S, Zwick D, Siegel S, Finlay J, Cairo MS; Children's Oncology Group. Shortened intensified multi-agent chemotherapy and non-cross resistant maintenance therapy for advanced lymphoblastic lymphoma in children and adolescent — View Citation

Lones MA, Perkins SL, Sposto R, Tedeschi N, Kadin ME, Kjeldsberg CR, Wilson JF, Zwick DL, Cairo MS. Non-Hodgkin's lymphoma arising in bone in children and adolescents is associated with an excellent outcome: a Children's Cancer Group report. J Clin Oncol. 2002 May 1;20(9):2293-301. — View Citation

Lowe EJ, Sposto R, Perkins SL, Gross TG, Finlay J, Zwick D, Abromowitch M; Children's Cancer Group Study 5941. Intensive chemotherapy for systemic anaplastic large cell lymphoma in children and adolescents: final results of Children's Cancer Group Study 5 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Estimate toxicity and feasibility of 11 month multiagent chemotx	Estimate the toxicity and feasibility of a short (11 month) aggressive multiagent chemotherapy regimen - Intensive NYI\NHL		No
Secondary	Provide preliminary data for a future phase III study			No
Secondary	Investigate the biology of lymphoblastic lymphoma	To continue to investigate the biology of lymphoblastic lymphoma and its relationship to leukemia through the study of immunophenotyping, cytogenetics and molecular analysis.		No
Secondary	Obtain preliminary data on treatment of anaplastic large cell	To obtain preliminary data on treatment of anaplastic large cell (Ki-1) and T-cell large cell lymphoma treated with intensive NYI.		No