Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

SC-PEG Asparaginase vs. Oncaspar in Pediatric Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Dana-Farber Cancer Institute
Sponsor:
Collaborators:
Sigma Tau
Information provided by (Responsible Party):
Lewis B. Silverman, M.D., Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01574274
First received: April 5, 2012
Last updated: September 4, 2014
Last verified: September 2014
  Purpose

This study is being conducted to learn about the effects of SC-PEG, which is a new form of a chemotherapy drug called asparaginase. Asparaginase is used to treat ALL and lymphoblastic lymphoma. The standard form of asparaginase, called Elspar, is given in the muscle once a week for 30 weeks. There are other forms of asparaginase. The investigators will be studying two of these: Oncaspar and Calaspargase Pegol (SC-PEG). The investigators have previously studied giving Oncaspar in the vein (instead of the muscle) every 2 weeks in patients with ALL, and have shown that this dosing did not lead to any more side effects than Elspar given weekly in the muscle. The study drug, SC-PEG, is very similar but not identical to Oncaspar. SC-PEG has been given in the vein to children and adolescents with ALL as part of other research studies, and it appears to last longer in the blood after a dose than Oncaspar. It has not yet been approved by the FDA. The goal of this research study is to learn whether the side effects and drug levels of SC-PEG given in the vein every 3 weeks are similar to Oncaspar given into the vein about every 2 weeks.

The study will also help to determine whether changing treatment for children and adolescents with ALL with high levels of minimal residual disease may improve cure rates. Measuring minimal disease (MRD) is a laboratory test that finds low levels of leukemia cells that the investigators cannot see under the microscope. In the past, it has been shown that children and adolescents with ALL with high levels of MRD after one month of treatment are less likely to be cured than those with low levels of MRD. Therefore, on the study, the bone marrow and blood at the end of the first month of treatment will be measured in participants with leukemia, and changes in therapy will be implemented based on this measurement. It is not known for sure that changing treatment will improve cure rates. MRD levels can only be measured if the marrow is filled with cancer cells at the time of diagnosis. Therefore, MRD studies will only be done in children and adolescents with ALL and not in those with lymphoblastic lymphoma.

Another part of the study is to determine whether giving antibiotics during the first month of treatment even to participants without fever will prevent serious infections in the blood and other parts of the body. About 25% of children and adolescents with ALL and lymphoblastic lymphoma who receive standard treatment develop a serious blood infection from a bacteria during the first month of treatment. Typically, antibiotics (medicines that fight bacteria) are given by vein only after a child with leukemia or lymphoma develops a fever or have other signs of infection. In this study, antibiotics will be given by mouth or in the vein to all participants during the first month of treatment, whether or not they develop fever.

Another goal of the study to learn how vitamin D levels relate to bone problems (such as broken bones or fractures) that children and adolescents with ALL and lymphoblastic lymphoma experience while on treatment. Some of the chemotherapy drugs used to treat ALL and lymphoblastic lymphoma can make bones weaker, which make fractures more likely. Vitamin D is a natural substance from food and sunlight that can help keep bones strong. The investigators will study how often participants have low levels of vitamin D while receiving chemotherapy, and, for those with low levels, whether giving vitamin D supplements will increase those levels.

Another focus of the study is to learn more about the biology of ALL and lymphoblastic lymphoma by doing research on blood, bone and spinal fluid bone marrow samples. The goal of this research is to improve treatment for children with leukemia in the future.


Condition Intervention Phase
Acute Lymphoblastic Leukemia
Lymphoblastic Lymphoma
Drug: SC-PEG
Drug: Oncaspar
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Study of Intravenous Calaspargase Pegol (SC-PEG Asparaginase) and Intravenous Oncaspar in Children and Adolescents With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Asparaginase-related toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Number of participants with adverse events related to asparaginase, including pancreatitis, thrombosis and hypersensitivity reactions

  • Asparaginase pharmacokinetics [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Serum asparaginase activity levels and asparaginase antibody levels, assayed immediately after 1st dose, then 4,11,18,and 25 days after 1st dose, and then prior to every dose of asparaginase given during post-induction phases of treatment.


Secondary Outcome Measures:
  • Frequency of Infections [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Number of episodes of bacteremia, fungemia and invasive fungal infections during the remission induction phase

  • Outcome [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Rates of complete remission, relapse, induction death, remission death, and second malignant neoplasms in participants

  • Outcome of participants with very-high risk disease [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Rates of relapse, remission death and second malignant neoplasm in participants with high MRD and/or high risk cytogenetics who are treated with a more intensified regimen

  • Feasibility of Vitamin D Screening/Supplementation [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Vitamin D-levels at various times during treatment, proportion of participants with low vitamin D levels, proportion of participants who agree to Vitamin D supplementation

  • Feasibility of prospective screening for ABGD [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Number of samples from participants with T-ALL in which a successful result was obtained by qPCR to assess absence of biallelic TCRy deletions (ABGD); frequency of ABGD in T-ALL

  • Feasibility of prospective screening for genetic abnormalities [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Number of samples from participants with B-ALL in which a successful result was obtained in prospective screening for abnormalities (eg, mutations, deletions, rearrangements) of IKZF1, CRLF2 and JAK1/2 in patients with newly diagnosed B-ALL; proportion of participants with B-ALL found to have one of these abnormlaties.

  • Relationship Between Apoptotic/Anti-apoptotic proteins and Response to CT [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Levels of pro- and anti-apoptotic proteins in participant samples from diagnosis; correlation of these levels to clinical response (induction failure, high MRD, relapse).


Estimated Enrollment: 240
Study Start Date: April 2012
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: SC-PEG
SC-PEG
Drug: SC-PEG
11 doses Intravenously over one hour
Active Comparator: Oncaspar
Oncaspar
Drug: Oncaspar
16 doses Intravenously over one hour

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   365 Days to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of ALL or lymphoblastic leukemia
  • No prior therapy except short courses of corticosteroids, a single dose of IT cytarabine or emergent radiation to the mediastinum or other life-threatening masses

Exclusion Criteria:

  • Have received more than 7 days of corticosteroids in the preceding 4 weeks or more than 28 days of corticosteroids in the preceding 6 months
  • Have received any chemotherapy or radiotherapy for previous malignancy
  • Receiving any other investigational agent
  • Known to be HIV positive
  • Uncontrolled intercurrent illness
  • Pregnant or breastfeeding
  • History of previous malignancy
  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: NCT01574274

Locations
United States, Massachusetts
Children's Hospital Boston Recruiting
Boston, Massachusetts, United States, 02215
Contact: Lewis Silverman, MD    617-632-6191    lewis_silverman@dfci.harvard.edu   
Principal Investigator: Lewis Silverman, MD         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Lewis Silverman, MD    617-632-6191    lewis_silverman@dfci.harvard.edu   
Principal Investigator: Lewis Silverman, MD         
United States, New York
Columbia University Medical Center, Morgan Stanley Children's Hospital of New York-Presbyterian Recruiting
New York, New York, United States, 10032
Contact: Kara Kelly, MD       kk291@columbia.edu   
Principal Investigator: Kara Kelly, MD         
Montefiore Medical Center Recruiting
New York, New York, United States, 10467
Contact: Peter Cole, MD       Peter.Cole@einstein.yu.edu   
Principal Investigator: Peter Cole, MD         
United States, Rhode Island
Hasbro Children's Hospital Recruiting
Providence, Rhode Island, United States, 02903
Contact: Jennifer Greene Welch, MD       jwelch@lifespan.org   
Principal Investigator: Jennifer Greene Welch, MD         
United States, Virginia
INOVA Fairfax Hospital Active, not recruiting
Falls Church, Virginia, United States, 22042
Canada, Ontario
McMaster University Recruiting
Hamilton, Ontario, Canada
Contact: Uma Athale, MD       athaleu@mcmaster.ca   
Principal Investigator: Uma Athale, MD         
Canada, Quebec
Hospital Sainte Justine, University of Montreal Recruiting
Montreal, Quebec, Canada
Contact: Jean-Marie LeClerc, MD       jean-marie.leclerc@umontreal.ca   
Principal Investigator: Jean-Marie LeClerc, MD         
Centre Hospitalier U. de Quebec Recruiting
Quebec City, Quebec, Canada
Contact: Bruno Michon, MD       bruno.michon@mail.chuq.qc.ca   
Principal Investigator: Bruno Michon, MD         
Puerto Rico
San Jorge Children's Hospital Active, not recruiting
San Juan, Puerto Rico
Sponsors and Collaborators
Dana-Farber Cancer Institute
Sigma Tau
  More Information

No publications provided

Responsible Party: Lewis B. Silverman, M.D., Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01574274     History of Changes
Other Study ID Numbers: 11-001
Study First Received: April 5, 2012
Last Updated: September 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Lymphoma
Lymphoma, Non-Hodgkin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Asparaginase
Pegaspargase
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014