Combination Chemotherapy and Radiation Therapy in Treating Patients With Acute Lymphoblastic Leukemia That Has Relapsed in the CNS or Testes

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00096135
First received: November 9, 2004
Last updated: August 4, 2014
Last verified: August 2014
  Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Giving combination chemotherapy together with radiation therapy may kill more cancer cells.

PURPOSE: This clinical trial is studying how well giving chemotherapy together with radiation therapy works in treating patients with acute lymphoblastic leukemia that has relapsed in the CNS and/or testes.


Condition Intervention
Leukemia
Biological: filgrastim
Drug: cyclophosphamide
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: dexamethasone
Drug: etoposide
Drug: leucovorin calcium
Drug: mercaptopurine
Drug: methotrexate
Drug: pegaspargase
Drug: therapeutic hydrocortisone
Drug: vincristine sulfate
Radiation: radiation therapy

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Late Isolated Extramedullary Relapse From Acute Lymphoblastic Leukemia (ALL) (Initial CR1≥ 18 Months)

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Event-free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Monitoring of efficacy results will be performed in comparison with historical results.

  • Toxicity graded using the NCI CTCAE version 4.0 [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]
    Tabulated and analyzed using descriptive statistics.


Enrollment: 168
Study Start Date: November 2004
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (combination chemotherapy)
All patients receive common induction (vincristine sulfate, dexamethasone, daunorubicin hydrochloride & intrathecal triple therapy (ITT: methotrexate, therapeutic hydrocortisone and cytarabine)), consolidation (cytarabine, pegaspargase, filgrastim, testicular radiation therapy for testicular patients only), re-induction (vincristine, dexamethasone, daunorubicin), and intensification chemotherapy (methotrexate, leucovorin calcium, mercaptopurine, etoposide, cyclophosphamide & ITT (see above). Patients are stratified to maintenance therapy according to site of extramedullary relapse (CNS vs testicular).
Biological: filgrastim
given subcutaneously (SC)
Other Names:
  • Granulocyte Colony-Stimulating Factor
  • r-metHuG-CSF
  • G-CSF
  • Neupogen
  • NSC 614629
Drug: cyclophosphamide
IV over 15-30 minutes
Other Names:
  • CYTOXAN
  • NSC #26271
Drug: cytarabine
IV over 3 hours twice daily
Other Names:
  • Cytosine arabinoside
  • Ara-C
  • Cytosar
  • NSC #6387
Drug: daunorubicin hydrochloride
IV over 15 minutes
Other Names:
  • Daunomycin
  • rubidomycin
  • Cerubidine
  • NSC #82151
Drug: dexamethasone
oral twice daily
Other Names:
  • Decadron
  • Hexadrol
  • Dexone
  • Dexameth
  • NSC #34521
Drug: etoposide
IV over 1 hour
Other Names:
  • VePesid
  • Etopophos
  • VP-16
  • NSC #141540
Drug: leucovorin calcium
rescue IV over 24 hours
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC 03590
Drug: mercaptopurine
oral
Other Names:
  • 6-MP
  • Purinethol
  • 6-mercaptopurine
  • NSC #000755
Drug: methotrexate
intramuscularly (IM)
Other Names:
  • MTX
  • amethopterin
  • Trexall
  • NSC #000740
Drug: pegaspargase
intramuscularly (IM)
Other Names:
  • PEG-asparaginase
  • PEGLA
  • PEG-L-asparaginase
  • polyethylene glycol-L-asparaginase
  • Oncaspar
  • NSC 624239
Drug: therapeutic hydrocortisone Drug: vincristine sulfate
given IV
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Radiation: radiation therapy
Patients with isolated testicular relapse will start Induction with a single dose of high-dose methotrexate (HDMTX) and will not receive either testicular or cranial radiation. Patients with isolated CNS relapse will NOT receive the initial dose of HDMTX prior to Induction, but will receive 1200 cGy of cranial radiation after completing the initial 12 months of intensive systemic chemotherapy.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Months to 29 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of acute lymphoblastic leukemia (ALL)

    • B-precursor lineage (T-precursor lineage closed to accrual as of 05/20/10)
    • In first bone marrow remission (M1 by morphology) AND duration of first complete remission ≥ 18 months from time of initial diagnosis
  • First isolated CNS and/or testicular relapse

    • Isolated CNS relapse, as defined by 1 of the following:

      • WBC ≥ 5/mm^3 in cerebrospinal fluid (CSF) with blasts present on cytospin
      • Any number of WBC in CSF with immunophenotypic proof of leukemic relapse, defined by the following:

        • Identifiable blasts AND 1 of the following:

          • B-lineage (TdT OR CD-10-positive on 2 consecutive CSF samples obtained 4 weeks apart)
          • T-lineage (TdT AND CD-7 OR TdT positivity alone on 2 consecutive CSF samples obtained 4 weeks apart) (Closed to accrual as of 05/20/10)
    • Isolated testicular relapse, defined as biopsy proven testicular involvement
  • No Down syndrome
  • No T-cell ALL or T-cell non-Hodgkin lymphoma
  • No known optic nerve and/or retinal involvement

PATIENT CHARACTERISTICS:

Age

  • 18 months to 29 years at relapse

Performance status

  • Karnofsky 30-100% (for patients > 16 years of age) OR
  • Lansky 30-100% (for patients ≤ 16 years of age)

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • Not specified

Renal

  • Creatinine adjusted according to age as follows:

    • No greater than 0.4 mg/dL (≤ 5 months)
    • No greater than 0.5 mg/dL (6 months -11 months)
    • No greater than 0.6 mg/dL (1 year-23 months)
    • No greater than 0.8 mg/dL (2 years-5 years)
    • No greater than 1.0 mg/dL (6 years-9 years)
    • No greater than 1.2 mg/dL (10 years-12 years)
    • No greater than 1.4 mg/dL (13 years and over [female])
    • No greater than 1.5 mg/dL (13 years to 15 years [male])
    • No greater than 1.7 mg/dL (16 years and over [male]) OR
  • Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min

Cardiovascular

  • Shortening fraction ≥ 27% by echocardiogram OR
  • Ejection fraction ≥ 50% by MUGA

Other

  • Not pregnant or nursing

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior bone marrow transplantation

Chemotherapy

  • Prior total anthracycline dosage ≤ 360 mg/m^2

Endocrine therapy

  • Not specified

Radiotherapy

  • Not specified

Surgery

  • Not specified

Other

  • No prior systemic therapy for concurrent extramedullary relapse
  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: NCT00096135

  Show 153 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Julio C. Barredo, MD University of Miami Miller School of Medicine-Sylvester Cancer Center
Study Chair: Caroline A. Hastings, MD Children's Hospital & Research Center Oakland
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00096135     History of Changes
Other Study ID Numbers: AALL02P2, CDR0000390345, COG-AALL02P2, NCI-2011-01623
Study First Received: November 9, 2004
Last Updated: August 4, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
recurrent childhood acute lymphoblastic leukemia
B-cell childhood acute lymphoblastic leukemia
T-cell childhood acute lymphoblastic leukemia
TdT positive childhood acute lymphoblastic leukemia

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

ClinicalTrials.gov processed this record on September 22, 2014