Total Therapy Study XVI for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by St. Jude Children's Research Hospital
Sponsor:
Collaborators:
Enzon Pharmaceuticals, Inc.
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00549848
First received: October 25, 2007
Last updated: May 13, 2014
Last verified: May 2014
  Purpose

The primary objective of this study (TOTXVI) is to compare the clinical benefit, the pharmacokinetics, and the pharmacodynamics of polyethylene glycol-conjugated (PEG) asparaginase given in higher dose (HD PEG) versus those of PEG-asparaginase given in conventional dose (CD PEG) during the continuation phase.

This study has several secondary objectives:

Therapeutic Objectives:

To estimate the event-free survival and overall survival of children with ALL who are treated with risk-directed therapy.

To study whether intensifying induction, including fractionated cyclophosphamide and thioguanine, in patients with day 15 MRD > 5%, will result in improved leukemia cytoreduction in this subgroup compared to TOTXV.

To assess whether intensification of central nervous system (CNS)-directed intrathecal and systemic chemotherapy will improve outcome in patients at high risk of CNS relapse.

Exploratory Pharmacologic Objectives:

To identify pharmacogenetic, pharmacokinetic and pharmacodynamic predictors for treatment-related outcomes in the context of the systemic therapy used in the protocol.

To compare the pharmacokinetics and pharmacodynamics of PEG-asparaginase given in higher dose (3,500 or 3,000 units/m2) versus those of PEG-asparaginase given in conventional dose (2,500 units/m2) in the continuation phase.

Exploratory Biologic Objectives:

To determine the prognostic value of levels of minimal residual disease in peripheral blood at day 8 of remission induction.

To validate new markers and methods for MRD detection. To genotype natural killer (NK) cell receptors and measure their expressions at diagnosis and before reinduction, and to associate these features with treatment outcome.

To identify new prognostic factors by applying new technologies to study patient material (e.g., stored plasma, serum, cerebrospinal fluid, and normal and leukemic cells).

Exploratory Neuroimaging Objectives:

To use quantitative MR measures (Diffusion Tensor Imaging and high resolution volumetric imaging) to assess differences in myelin and cortical thickness development in patients treated for ALL relative to healthy controls matched for age and gender.

To assess the impact of folate pathway genetic polymorphisms on myelin and cortical thickness development and neurocognitive performance.

To assess the impact of frontal-parietal lobe myelin and cortical thickness development on neurocognitive performance in attention, working memory, fluency, visual-spatial reasoning and processing speed.


Condition Intervention Phase
Acute Lymphoblastic Leukemia
Drug: Prednisone, Vincristine, Daunorubicin, PEG-L-asparaginase, Erwinia L-asparaginase, Doxorubicin, Cyclophosphamide, Cytarabine, Thioguanine
Drug: Clofarabine, Methotrexate, Mercaptopurine, Dexamethasone, Etoposide, Dasatinib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Total Therapy Study XVI for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • Continuous complete remission of patients receiving high-dose and conventional dose PEG-asparaginase. [ Time Frame: 3.5 years after the last enrollment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Event-free survival [ Time Frame: 3.5 years after the last enrollment ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 3.5 years after the last enrollment ] [ Designated as safety issue: No ]
  • Level of minimal residual disease (MRD) on the 15th day of remission induction [ Time Frame: 3.5 years after enrollment of last patient ] [ Designated as safety issue: No ]
    To study whether intensifying induction, including fractionated cyclophosphamide and thioguanine, in patients with day 15 MRD> 5% will result in improved leukemia cytoreduction in this subgroup compared to therapy followed in the TOTXV protocol.

  • Time to CNS relapse or the last follow up since diagnosis [ Time Frame: 3.5 years after enrollment of last patient ] [ Designated as safety issue: No ]
    To assess whether intensification of CNS-directed intrathecal and systemic chemotherapy will improve outcome in patients at high-risk of CNS relapse.


Estimated Enrollment: 420
Study Start Date: October 2007
Estimated Study Completion Date: November 2019
Estimated Primary Completion Date: November 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HD PEG

Participants randomized to receive higher dose PEG-asparaginase during the continuation phase.

Interventions:

  • Prednisone, Vincristine, Daunorubicin, PEG-L-asparaginase, Erwinia L-asparaginase, Doxorubicin, Cyclophosphamide, Cytarabine, Thioguanine
  • Clofarabine, Methotrexate, Mercaptopurine, Dexamethasone, Etoposide, Dasatinib
Drug: Prednisone, Vincristine, Daunorubicin, PEG-L-asparaginase, Erwinia L-asparaginase, Doxorubicin, Cyclophosphamide, Cytarabine, Thioguanine
See Detailed Description section for details of treatment interventions.
Other Names:
  • Prednisone: prednisolone
  • Vincristine: Oncovin(R)
  • Daunorubicin: daunomycin, Cerubidine(R)
  • PEG-L-asparaginase: pegaspargase, Oncaspar(R)
  • Erwinia L-Asparaginase: Erwinase(R)
  • Doxorubicin: Adriamycin(R)
  • Cyclophosphamide: Cytoxan(R)
  • Cytarabine: Ara-C, Cytosar-U(R)
  • Thioguanine: 6-TG
Drug: Clofarabine, Methotrexate, Mercaptopurine, Dexamethasone, Etoposide, Dasatinib
See Detailed Description section for details of treatment interventions.
Other Names:
  • Clofarabine: clofarex, Clolar(TM)
  • Methotrexate: MTX
  • Mercaptopurine: 6-MP, Purinethol(R)
  • Dexamethasone: Decadron(R)
  • Etoposide: VP-16, Vepesid(R)
  • Dasatinib: Sprycel(R)
Active Comparator: CD PEG

Participants randomized to receive conventional dose PEG-asparaginase during the continuation phase..

Interventions:

  • Prednisone, Vincristine, Daunorubicin, PEG-L-asparaginase, Erwinia L-asparaginase, Doxorubicin, Cyclophosphamide, Cytarabine, Thioguanine
  • Clofarabine, Methotrexate, Mercaptopurine, Dexamethasone, Etoposide, Dasatinib
Drug: Prednisone, Vincristine, Daunorubicin, PEG-L-asparaginase, Erwinia L-asparaginase, Doxorubicin, Cyclophosphamide, Cytarabine, Thioguanine
See Detailed Description section for details of treatment interventions.
Other Names:
  • Prednisone: prednisolone
  • Vincristine: Oncovin(R)
  • Daunorubicin: daunomycin, Cerubidine(R)
  • PEG-L-asparaginase: pegaspargase, Oncaspar(R)
  • Erwinia L-Asparaginase: Erwinase(R)
  • Doxorubicin: Adriamycin(R)
  • Cyclophosphamide: Cytoxan(R)
  • Cytarabine: Ara-C, Cytosar-U(R)
  • Thioguanine: 6-TG
Drug: Clofarabine, Methotrexate, Mercaptopurine, Dexamethasone, Etoposide, Dasatinib
See Detailed Description section for details of treatment interventions.
Other Names:
  • Clofarabine: clofarex, Clolar(TM)
  • Methotrexate: MTX
  • Mercaptopurine: 6-MP, Purinethol(R)
  • Dexamethasone: Decadron(R)
  • Etoposide: VP-16, Vepesid(R)
  • Dasatinib: Sprycel(R)

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • Participant has a confirmed diagnosis of precursor B-cell or precursor T-cell acute lymphocytic leukemia (ALL) by immunophenotyping
  • Participant is less than or equal to 18 years of age
  • Limited prior therapy, including systemic glucocorticoids for one week or less, one dose of vincristine, emergency radiation therapy to the mediastinum and one dose of intrathecal chemotherapy. Other circumstances must be cleared by principal investigator (PI) or co-PI.
  • Written, informed consent and assent following Institutional Review Board, NCI, FDA, and Office for Human Research Protections (OHRP) Guidelines.

Exclusion Criteria:

  • Participants with prior therapy, other than that listed above
  • Pregnant or lactating
  • Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.
  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: NCT00549848

Contacts
Contact: Sima Jeha, MD 1-866-278-5833 info@stjude.org

Locations
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Principal Investigator: Sima Jeha, MD         
Sponsors and Collaborators
St. Jude Children's Research Hospital
Enzon Pharmaceuticals, Inc.
Investigators
Principal Investigator: Sima Jeha, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided by St. Jude Children's Research Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00549848     History of Changes
Other Study ID Numbers: TOTXVI, 5R01CA140729, 5F32CA141762, R37CA036401, 5R01CA090246, Aspar PK-PD-T16
Study First Received: October 25, 2007
Last Updated: May 13, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by St. Jude Children's Research Hospital:
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
Methotrexate
Cytarabine
6-Mercaptopurine
Liposomal doxorubicin
Etoposide phosphate
Clofarabine
Pegaspargase
Dexamethasone
Doxorubicin
Prednisone
Etoposide
Vincristine
Asparaginase
Daunorubicin
Thioguanine
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Dasatinib
Immunosuppressive Agents

ClinicalTrials.gov processed this record on October 16, 2014