Full Text View
Tabular View
No Study Results Posted
Related Studies
Bortezomib and Combination Chemotherapy in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Acute Lymphoblastic Lymphoma
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), May 2009
First Received: March 31, 2009   Last Updated: May 2, 2009   History of Changes
Sponsors and Collaborators: Children's Oncology Group
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00873093
  Purpose

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying the side effects of giving bortezomib together with combination chemotherapy and to see how well it works in treating young patients with relapsed acute lymphoblastic leukemia or acute lymphoblastic lymphoma.


Condition Intervention Phase
Leukemia
Lymphoma
Biological: filgrastim
Drug: asparaginase
Drug: bortezomib
Drug: cyclophosphamide
Drug: cytarabine
Drug: doxorubicin hydrochloride
Drug: etoposide phosphate
Drug: leucovorin calcium
Drug: methotrexate
Drug: pegaspargase
Drug: prednisone
Drug: therapeutic hydrocortisone
Drug: vincristine sulfate
Phase II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Lymphoma
Drug Information available for: Hydrocortisone acetate Cyclophosphamide Hydrocortisone Prednisone Vincristine Leucovorin Methotrexate Cytarabine hydrochloride Doxorubicin Doxorubicin hydrochloride Etoposide Citrovorum factor Proctofoam-HC Hydrocortisone hemisuccinate Hydrocortamate Myocet Etoposide phosphate Filgrastim Pegaspargase Bortezomib Hydrocortisone 21-sodium succinate Cytarabine Hydrocortisone cypionate Leucovorin Calcium Vincristine sulfate Cortisol succinate Cortisol 21-phosphate Folinic acid calcium salt pentahydrate L-Asparaginase
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: A Phase II Pilot Trial of Bortezomib (PS-341, Velcade®, IND #58,443) in Combination With Intensive Re-Induction Therapy for Children With Relapsed Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma (LL)

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

Primary Outcome Measures:
  • Toxicity as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  • Second complete remission rate at the end of block 1 reinduction chemotherapy [ Designated as safety issue: No ]
  • Event-free survival at 4 months [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Minimal residual disease [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: March 2009
Estimated Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To estimate the toxicity of bortezomib in combination with intensive reinduction chemotherapy in young patients with relapsed acute lymphoblastic leukemia or acute lymphoblastic lymphoma.
  • To estimate the second complete remission rate at the end of block 1 reinduction chemotherapy and the 4-month event-free survival of these patients.

Secondary

  • To assess minimal residual disease in bone marrow following completion of each block of reinduction chemotherapy.

OUTLINE: This is a multicenter study.

  • Reinduction block 1: Patients receive cytarabine intrathecally (IT) on day 1; vincristine sulfate IV on days 1, 8, 15, and 22; doxorubicin hydrochloride IV over 15 minutes on day 1; oral prednisone twice daily on days 1-29; bortezomib IV on days 1, 4, 8, and 11; and pegaspargase intramuscularly (IM) on days 2, 8, 15, and 22. Patients with CNS-negative disease (CNS1 or CNS2) also receive methotrexate IT on days 15 and 29; patients with CNS-positive disease (CNS3) receive triple intrathecal therapy (TIT) comprising methotrexate, hydrocortisone, and cytarabine IT on days 8, 15, 22, and 29. After completion of reinduction block 1, patients with acute lymphoblastic leukemia (ALL) and M2 or M3 bone marrow proceed directly to reinduction block 2. Patients with ALL and M1 bone marrow or acute lymphoblastic lymphoma proceed to reinduction block 2 after blood counts recover.

Patients with persistent CSF blasts after 6 doses of TIT or patients with progressive acute lymphoblastic lymphoma are removed from the study.

  • Reinduction block 2: Patients receive etoposide phosphate IV over 1-2 hours on days 1-5; cyclophosphamide IV over 1 hour on days 1-5; bortezomib IV on days 1, 4, and 8; filgrastim (G-CSF) subcutaneously (SC) or IV daily beginning on day 6 and continuing until blood counts recover*; high-dose methotrexate IV on day 22; and leucovorin calcium orally or IV every 6 hours on days 23 and 24. Patients with CNS-negative disease also receive methotrexate IT on days 1 and 22; patients with CNS-positive disease receive TIT on days 1 and 22. After completion of reinduction block 2, patients proceed to reinduction block 3 immediately or when blood counts recover. Patients with disease progression are removed from the study.

NOTE: *Patients do not receive G-CSF on day 8.

  • Reinduction block 3: Patients receive cytarabine IV over 3 hours twice daily on days 1, 2, 8, and 9; L-asparaginase IM on days 2 and 9; and G-CSF SC or IV daily beginning on day 10 and continuing until blood counts recover. After completion of study treatment, patients are followed every 6 months for 3 years and then annually for 2 years.
  Eligibility

Ages Eligible for Study:   1 Year to 31 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following:

    • Pre-B acute lymphoblastic leukemia (ALL) in first early (< 36 months from diagnosis) isolated bone marrow or combined bone marrow/extramedullary relapse as documented by histology and immunophenotyping
    • T-cell ALL in first isolated bone marrow or combined relapse as documented by histology and immunophenotyping
    • T-cell acute lymphoblastic lymphoma in first relapse as documented by histology

      • Measurable disease as documented by clinical, radiographic, or histologic criteria
  • Relapsed or refractory to conventional therapy
  • No Ph+ ALL unless refractory to ≥ 1 tyrosine kinase inhibitor therapy

    • Patients who are unable to tolerate tyrosine kinase inhibitor therapy due to toxicity are eligible
  • No mature B-cell ALL (i.e., sIg positive and kappa or lambda restricted positivity) with FAB L3 morphology and/or myc translocation
  • No known optic nerve and/or retinal involvement

    • Patients presenting with visual disturbances should have an ophthalmological exam and, if indicated, an MRI to determine optic nerve or retinal involvement
  • No extramedullary disease (i.e., isolated CNS disease or isolated testicular disease)
  • No concurrent genetic syndrome (e.g., Down syndrome, Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone marrow failure syndrome)

PATIENT CHARACTERISTICS:

  • Karnofsky performance status (PS) 60-100% (for patients > 16 years of age) OR Lansky PS 60-100% (for patients ≤ 16 years of age)
  • Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR maximum serum creatinine based on age/gender as follows:

    • 0.4 mg/dL (for patients 1 to 5 months of age)
    • 0.5 mg/dL (for patients 6 to 11 months of age)
    • 0.6 mg/dL (for patients 1 year of age)
    • 0.8 mg/dL (for patients 2 to 5 years of age)
    • 1 mg/dL (for patients 6 to 9 years of age)
    • 1.2 mg/dL (for patients 10 to 12 years of age)
    • 1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)
    • 1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients ≥ 16 years of age)
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
  • ALT < 3 times ULN for age (unless elevation due to leukemia infiltration)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by gated radionuclide study
  • Pulse oximetry ≥ 94% at sea level (> 90% if at high altitude)
  • No evidence of dyspnea at rest or exercise intolerance
  • No evidence of acute pulmonary infiltrates on chest radiograph
  • No known allergy to doxorubicin, cytarabine, etoposide, etoposide phosphate, boron, mannitol, or bortezomib
  • No CNS toxicity > grade 2
  • Seizure disorder allowed provided patient is on anticonvulsants (e.g., benzodiazepines or gabapentin) and it is well controlled
  • Able to receive asparaginase (i.e., no prior severe pancreatitis, stroke, or other toxicity)

    • Patients who initially receive asparaginase but discontinue drug due to toxicity are eligible
    • Patients with prior allergies to pegaspargase that are clinically significant are eligible provided Erwinia L-asparaginase can be substituted

PRIOR CONCURRENT THERAPY:

  • Fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy (for patients who relapse on therapy other than standard ALL maintenance therapy)*
  • No prior cumulative anthracycline exposure > 400 mg/m²
  • No prior bortezomib or other proteasome inhibitors
  • No prior reinduction attempts or treatment for prior extramedullary relapse

    • Patients with primary induction failure are not eligible
  • At least 14 days since prior cytotoxic therapy (24 hours for hydroxyurea)
  • At least 7 days since prior anticancer biologic agents or donor lymphocyte infusions
  • At least 4 months since prior stem cell transplant or rescue

    • No evidence of active graft-vs-host disease (GVHD)
  • No concurrent GVHD prophylaxis
  • No concurrent anticonvulsants known to activate the cytochrome p450 system (e.g., phenytoin, carbamazepine, and phenobarbital)

    • Concurrent benzodiazepines or gabapentin allowed
  • No concurrent corticosteroids (including steroids as antiemetics) except as treatment or prophylaxis for anaphylactic reactions OR treatment for pulmonary toxicity
  • No other concurrent anticancer chemotherapy or immunomodulating agents NOTE: *Patients who relapse while receiving standard ALL maintenance chemotherapy will not be required to undergo a waiting period prior to entry onto this study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00873093

Locations
United States, California
Children's Hospital Central California Recruiting
Madera, California, United States, 93638-8762
Contact: Vonda L. Crouse     559-353-5480        
Children's Hospital of Orange County Recruiting
Orange, California, United States, 92868
Contact: Violet Shen     714-532-8636        
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94115
Contact: Clinical Trials Office - UCSF Helen Diller Family Comprehensi     877-827-3222        
United States, Florida
Lee Cancer Care of Lee Memorial Health System Recruiting
Fort Myers, Florida, United States, 33901
Contact: Clinical Trials Office - Lee Cancer Care of Lee Memorial Healt     877-680-0008        
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202-5289
Contact: Clinical Trials Office - Indiana University Cancer Center     317-274-2552        
United States, Kentucky
Lucille P. Markey Cancer Center at University of Kentucky Recruiting
Lexington, Kentucky, United States, 40536-0093
Contact: Clinical Trials Office - Markey Cancer Center at University of     859-257-3379        
United States, New York
SUNY Upstate Medical University Hospital Recruiting
Syracuse, New York, United States, 13210
Contact: Clinical Trials Office - SUNY Upstate Medical University Hospi     315-464-5476        
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229-3039
Contact: Clinical Trials Office - Cincinnati Children's Hospital Medica     513-636-0161        
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Terzah M. Horton, MD, PhD Texas Children's Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Oncology Group - Group Chair Office ( Gregory H. Reaman )
Study ID Numbers: CDR0000638413, COG-AALL07P1
Study First Received: March 31, 2009
Last Updated: May 2, 2009
ClinicalTrials.gov Identifier: NCT00873093     History of Changes
Health Authority: Unspecified

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

Study placed in the following topic categories:
Anti-Inflammatory Agents
Prednisone
Hydrocortisone
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Hormones
Pegaspargase
Methotrexate
Etoposide
Asparaginase
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Antineoplastic Agents, Hormonal
Vincristine
Glucocorticoids
Doxorubicin
Protease Inhibitors
Folic Acid
Hydrocortisone acetate
Lymphoma, Non-Hodgkin
Antineoplastic Agents, Phytogenic
Acute Lymphoblastic Leukemia, Childhood
Antimetabolites
Leukemia, Lymphoid
Immunologic Factors
Leucovorin
Cyclophosphamide
Etoposide phosphate
Lymphoblastic Lymphoma
Leukemia

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Prednisone
Anti-Infective Agents
Hydrocortisone
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Hormones
Pegaspargase
Therapeutic Uses
Abortifacient Agents
Methotrexate
Dermatologic Agents
Etoposide
Nucleic Acid Synthesis Inhibitors
Asparaginase
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Antineoplastic Agents, Hormonal
Immune System Diseases
Vincristine
Abortifacient Agents, Nonsteroidal
Glucocorticoids
Doxorubicin
Protease Inhibitors
Neoplasms
Hydrocortisone acetate
Lymphoma, Non-Hodgkin
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on May 07, 2009