Combination Chemotherapy With or Without Bortezomib in Treating Younger Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or Stage II-IV T-Cell Lymphoblastic Lymphoma

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02112916
First received: April 9, 2014
Last updated: August 12, 2014
Last verified: April 2014
  Purpose

This randomized phase III clinical trial compares how well combination chemotherapy works when given with or without bortezomib in treating patients with newly diagnosed T-cell acute lymphoblastic leukemia or stage II-IV T-cell lymphoblastic lymphoma. Bortezomib may help reduce the number of leukemia or lymphoma cells by blocking some of the enzymes needed for cell growth. It may also help chemotherapy work better by making cancer cells more sensitive to the drugs. It is not yet known if giving standard chemotherapy with or without bortezomib is more effective in treating T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. .


Condition Intervention Phase
Contiguous Stage II Adult Lymphoblastic Lymphoma
Noncontiguous Stage II Adult Lymphoblastic Lymphoma
Stage II Childhood Lymphoblastic Lymphoma
Stage III Adult Lymphoblastic Lymphoma
Stage III Childhood Lymphoblastic Lymphoma
Stage IV Adult Lymphoblastic Lymphoma
Stage IV Childhood Lymphoblastic Lymphoma
T-cell Adult Acute Lymphoblastic Leukemia
T-cell Childhood Acute Lymphoblastic Leukemia
Untreated Adult Acute Lymphoblastic Leukemia
Untreated Childhood Acute Lymphoblastic Leukemia
Drug: bortezomib
Drug: cytarabine
Drug: vincristine sulfate
Drug: dexamethasone
Drug: daunorubicin hydrochloride
Drug: pegaspargase
Drug: methotrexate
Drug: cyclophosphamide
Drug: mercaptopurine
Drug: doxorubicin hydrochloride
Drug: thioguanine
Drug: hydrocortisone sodium succinate
Drug: ifosfamide
Drug: leucovorin calcium
Drug: etoposide
Radiation: radiation therapy
Other: laboratory biomarker analysis
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Randomized Trial Investigating Bortezomib (NSC# 681239) on a Modified Augmented BFM (ABFM) Backbone in Newly Diagnosed T- Lymphoblastic Leukemia (T-ALL) and T- Lymphoblastic Lymphoma (T-LLy)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • EFS between modified ABFM backbone with or without bortezomib in all randomized patients [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Interim monitoring for efficacy and futility will be performed. The study will also be monitored for futility using the method of Freidlin and Korn.


Secondary Outcome Measures:
  • EFS [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Compared for isolated CNS, isolated bone marrow, and combined bone marrow relapse between IR patients on the non-bortezomib containing arm on this study (no CRT) with similar patients on AALL0434 (+ CRT).

  • Cumulative incidence rates [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Compared for isolated CNS, isolated bone marrow, and combined bone marrow relapse between IR patients on the non-bortezomib containing arm on this study (no CRT) with similar patients on AALL0434 (+ CRT).

  • Incidence of toxicity associated with modified standard therapy, including dexamethasone and additional pegaspargase as graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
    Safety data will also be compared between the two arms.

  • EFS between VHR T-ALL patients treated with HR BFM intensification blocks who become MRD negative and those who remain MRD positive at the end of HR Block 3 [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    The proportion of VHR T-ALL patients with EOC MRD >= 0.1% who become MRD negative (MRD undetectable) after the three high-risk BFM blocks of therapy, will be estimated. EFS for these patients (who continue on chemotherapy) will be compared with those who continue to have detectable MRD and who may receive other treatment options including hematopoietic stem cell transplant. Comparison will be descriptive.

  • EFS between VHR T-LLy patients treated with HR BFM intensification blocks who have partial remission (PR) or complete remission (CR) with those who do not respond (NR) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Comparison will be descriptive.


Estimated Enrollment: 1400
Study Start Date: April 2014
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A (combination chemotherapy)
Patients receive combination chemotherapy without bortezomib. See Detailed Description.
Drug: cytarabine
Given IT, IV, or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: dexamethasone
Given PO or IV
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Drug: pegaspargase
Given IV
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IT, IV, or PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: mercaptopurine
Give PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
Drug: thioguanine
Given PO
Other Name: 6-TG
Drug: hydrocortisone sodium succinate
Given IT
Other Names:
  • Sodium hydrocortisone succinate
  • Solu-Cortef
  • Solu-Glyc
Drug: ifosfamide
Given IV
Other Names:
  • Cyfos
  • Holoxan
  • IFF
  • IFX
  • IPP
Drug: leucovorin calcium
Given PO or IV
Other Names:
  • CF
  • CFR
  • LV
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm B (combination chemotherapy, bortezomib)
Patients receive combination chemotherapy with bortezomib. See Detailed Description.
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Drug: cytarabine
Given IT, IV, or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: dexamethasone
Given PO or IV
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Drug: pegaspargase
Given IV
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IT, IV, or PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: mercaptopurine
Give PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
Drug: thioguanine
Given PO
Other Name: 6-TG
Drug: hydrocortisone sodium succinate
Given IT
Other Names:
  • Sodium hydrocortisone succinate
  • Solu-Cortef
  • Solu-Glyc
Drug: ifosfamide
Given IV
Other Names:
  • Cyfos
  • Holoxan
  • IFF
  • IFX
  • IPP
Drug: leucovorin calcium
Given PO or IV
Other Names:
  • CF
  • CFR
  • LV
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   2 Years to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must be enrolled on Project: Every Child (APEC14B1) prior to treatment and enrollment on AALL1231
  • Patients must have newly diagnosed T-lymphoblastic leukemia (T-ALL) or T-lymphoblastic lymphoma (T-LLy) stages II-IV

    • Note: a diagnosis of T-ALL is established when leukemic blasts lack myeloperoxidase or evidence of B-lineage derivation (cluster of differentiation [CD]19/CD22/CD20), and express either surface or cytoplasmic CD3 or two or more of the antigens CD8, CD7, CD5, CD4, CD2 or CD1a, and are present either in peripheral blood or > 25% in the bone marrow; if surface CD3 is expressed on all leukemic cells, additional markers of immaturity, including terminal deoxynucleotidyl transferase (TdT), CD34 or CD99 will be assessed for expression; cases with uncertain expression will receive additional review within the appropriate Children's Oncology Group (COG) reference laboratory
    • For T-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to T-ALL; for tissue processed by other means (i.e. paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of T-LLy defined by the submitting institution will be accepted
  • All patients and/or their parents or legal guardians must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines

Exclusion Criteria:

  • Patients must not have received any cytotoxic chemotherapy for either the current diagnosis of T-ALL, T-L-Ly or for any cancer diagnosis prior to the initiation of protocol therapy on AALL1231, with the exception of:

    • Steroid pretreatment (60mg/m2/day prednisone [or 48 mg/m2/day of methylprednisolone] for =< 120 [5 days] hours in the 7 days prior to initiating Induction chemotherapy or for =< 336 hours [14 days] in the 28 days prior to initiating induction chemotherapy); prior exposure to ANY steroids that occurred > 28 days before the initiation of protocol therapy does not affect eligibility
    • Intrathecal cytarabine; or
    • 600 cGy of chest irradiation, if medically necessary
    • * Pre-treatment with dexamethasone in the 28 days prior to initiation of protocol therapy is not allowed
  • Pre-existing >= grade 2 sensory or motor peripheral neurotoxicity
  • Uncontrolled seizure disorder
  • Diagnosis of Down syndrome (Trisomy 21)
  • Patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential
  • Lactating females who plan to breastfeed
  • Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
  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: NCT02112916

Locations
United States, Pennsylvania
Children's Oncology Group Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: David T. Teachey    267-426-5802    teacheyd@email.chop.edu   
Principal Investigator: David T. Teachey         
Sponsors and Collaborators
Investigators
Principal Investigator: David Teachey Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02112916     History of Changes
Other Study ID Numbers: NCI-2014-00712, NCI-2014-00712, AALL1231, AALL1231, U10CA180886, U10CA098543
Study First Received: April 9, 2014
Last Updated: August 12, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Leukemia
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
6-Mercaptopurine
Cytarabine
Methotrexate
Thioguanine
Cyclophosphamide
Liposomal doxorubicin
Isophosphamide mustard
Pegaspargase
Bortezomib
Asparaginase
Daunorubicin
Dexamethasone
Doxorubicin
Etoposide
Ifosfamide
Vincristine
BB 1101
Dexamethasone acetate

ClinicalTrials.gov processed this record on August 26, 2014