Bortezomib and Combination Chemotherapy in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

This study has suspended participant recruitment.
(Temporarily Closed to Accrual)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00873093
First received: March 31, 2009
Last updated: April 9, 2014
Last verified: April 2014
  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 lymphoblastic lymphoma. 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.


Condition Intervention Phase
B-cell Adult Acute Lymphoblastic Leukemia
B-cell Childhood Acute Lymphoblastic Leukemia
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Lymphoblastic Lymphoma
T-cell Adult Acute Lymphoblastic Leukemia
T-cell Childhood Acute Lymphoblastic Leukemia
Drug: asparaginase
Drug: doxorubicin hydrochloride
Drug: therapeutic hydrocortisone
Drug: liposomal vincristine sulfate
Drug: cytarabine
Drug: prednisone
Drug: bortezomib
Drug: pegaspargase
Drug: methotrexate
Drug: etoposide phosphate
Drug: cyclophosphamide
Biological: filgrastim
Drug: leucovorin calcium
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: 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)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Second complete remission rate at the end of block 1 reinduction chemotherapy [ Time Frame: 29 days ] [ Designated as safety issue: No ]
    Descriptive statistics will be used to assess CR2 rates by stratum including calculation of 95% confidence intervals.

  • Bortezomib concentrations in patients receiving multi-agent combination therapy [ Time Frame: Day 8 of blocks 1 and 2 ] [ Designated as safety issue: No ]
  • Toxicity according to NCI CTCAE v4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Minimal residual disease [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    A one-sample Z-test of proportions (one-sided, alpha= 5%) will be used.


Estimated Enrollment: 60
Study Start Date: March 2009
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (bortezomib and combination chemotherapy)
See Detailed Description
Drug: asparaginase
Given IM
Other Names:
  • ASNase
  • Colaspase
  • Crasnitin
  • Elspar
  • L-ASP
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: therapeutic hydrocortisone
Given IT
Other Names:
  • Aeroseb-HC
  • Barseb HC
  • Cetacort
  • Cort-Dome
  • Cortef
Drug: liposomal vincristine sulfate
Given IV
Other Names:
  • liposomal vincristine
  • Marqibo
  • vincristine liposomal
  • vincristine sulfate liposome injection
Drug: cytarabine
Given IT or IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: prednisone
Given orally
Other Names:
  • DeCortin
  • Deltra
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Drug: pegaspargase
Given IM
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IT or IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: etoposide phosphate
Given IV
Other Names:
  • ETOP
  • Etopophos
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Biological: filgrastim
Given IV or SC
Other Names:
  • G-CSF
  • Neupogen
Drug: leucovorin calcium
Given IV or orally
Other Names:
  • CF
  • CFR
  • LV
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • 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 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 Philadelphia chromosome-positive (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 French-American-British Cooperative Group (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, a magnetic resonance imaging (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)
  • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky 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
  • Serum glutamate pyruvate transaminase (SPGT) (alanine aminotransferase [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
  • Patients who relapse on therapy other than standard ALL maintenance therapy must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study

    • At least 14 days since the completion of cytotoxic therapy with the exception of hydroxyurea, which is permitted up to 24 hours prior to the start of protocol therapy
    • At least 7 days since the completion of therapy with a biologic agent or donor lymphocyte infusions (DLI); for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
    • Stem cell transplant or rescue: no evidence of active graft-vs-host disease (GVHD) and ≥ 4 months must have elapsed; must not be receiving GVHD prophylaxis
  • 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
  • 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
  • Patients who relapse while receiving standard ALL maintenance chemotherapy will not be required to have a waiting period before entry onto this study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00873093

  Show 169 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Terzah Horton Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00873093     History of Changes
Other Study ID Numbers: NCI-2011-01908, NCI-2011-01908, CDR0000638413, AALL07P1, AALL07P1, U10CA098543
Study First Received: March 31, 2009
Last Updated: April 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Etoposide phosphate
Pegaspargase
Bortezomib
Asparaginase
Cyclophosphamide
Cytarabine
Doxorubicin
Etoposide
Methotrexate
Prednisone
Vincristine
Lenograstim
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone
Hydrocortisone-17-butyrate
Leucovorin
Levoleucovorin

ClinicalTrials.gov processed this record on April 15, 2014