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

NCT01574274 | Active Not Recruiting Phase 2 Results DMC

• 1 other identifier: 11-001
• Study Type: interventional
• Target: 240
• Locations: 2 countries
• Sites: 8

Brief Summary

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.

Conditions

Lymphoblastic Lymphoma; Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Asparaginase-Related Toxicity

  Asparaginase-related toxicity rate is defined as the percentage of patients who experience allergy (all grades), symptomatic pancreatitis (grade 2 or worse), thrombotic or bleeding complications requiring intervention (grade 2 or worse) with treatment attribution of possibly, probably or definite based on Common Terminology Criteria for Adverse Events (CTCAE) v4.

  30-week post-induction asparaginase treatment period. Toxicities assessed on an ongoing basis (at least 1 per month) while participant is on study, an average of 2 years.

• Induction and Post-Induction Nadir Serum Asparaginase Activity Level

  Nadir serum asparaginase activity (NSAA) levels were estimated based on established methods.

  Samples for nadir serum asparaginase activity levels were assayed at 4,11,18,and 25 days after 1st dose, and then prior to asparaginase dose given during post-induction, at Week 7, 13, 19, and 25.

Secondary Outcomes (7)

• Frequency of Infections

  2 years

• Outcome

  2 years

• Outcome of Participants With Very-high Risk Disease

  2 years

• Feasibility of Vitamin D Screening/Supplementation

  2 years

• Feasibility of Prospective Screening for ABGD

  2 years

Study Arms (2)

SC-PEG (Arm A)

ACTIVE COMPARATOR

Patients in this arm were randomized to receive IV Calaspargase Pegol (SC-PEG) 2500 IU/m2, administered as a single dose during induction and for 30 weeks post-induction. In the post-induction phases, IV SC-PEG was administered every 3 weeks (for a total of 10 post-induction doses). Protocol therapy was comprised of 5 phases: Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.

Drug: SC-PEG

Oncaspar (Arm B)

ACTIVE COMPARATOR

Patients in this arm were randomized to receive IV Oncaspar 2500 IU/m2, administered as a single dose during induction and for 30 weeks post-induction. In the post-induction phases, IV Oncaspar was administered every 2 weeks (for a total of 15 post-induction doses). Protocol therapy was comprised of 5 phases: Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.

Drug: Oncaspar

Interventions

Oncaspar DRUG

16 doses Intravenously over one hour

Oncaspar (Arm B)

SC-PEG DRUG

11 doses Intravenously over one hour

SC-PEG (Arm A)

Eligibility Criteria

• Age: 365 Days - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shire: collaborator
• National Cancer Institute (NCI): collaborator
• Dana-Farber Cancer Institute: lead

Study Sites (8)

Children's Hospital Boston

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Columbia University Medical Center, Morgan Stanley Children's Hospital of New York-Presbyterian

New York, New York, 10032, United States

Location

Montefiore Medical Center

New York, New York, 10467, United States

Location

Hasbro Children's Hospital

Providence, Rhode Island, 02903, United States

Location

McMaster University

Hamilton, Ontario, Canada

Location

Hospital Sainte Justine, University of Montreal

Montreal, Quebec, Canada

Location

Centre Hospitalier U. de Quebec

Québec, Quebec, Canada

Location

Related Publications (3)

• Vrooman LM, Blonquist TM, Stevenson KE, Supko JG, Hunt SK, Cronholm SM, Koch V, Kay-Green S, Athale UH, Clavell LA, Cole PD, Harris MH, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Place AE, Schorin MA, Welch JJG, Neuberg DS, Sallan SE, Silverman LB. Efficacy and Toxicity of Pegaspargase and Calaspargase Pegol in Childhood Acute Lymphoblastic Leukemia: Results of DFCI 11-001. J Clin Oncol. 2021 Nov 1;39(31):3496-3505. doi: 10.1200/JCO.20.03692. Epub 2021 Jul 6.

  PMID: 34228505 RESULT

• Cole PD, Kim SY, Li Y, Schembri A, Kelly KM, Sulis ML, Vrooman L, Welch JJG, Ramjan S, Silverman LB, Sands SA. Feasibility of serial neurocognitive assessment using Cogstate during and after therapy for childhood leukemia. Support Care Cancer. 2023 Jan 10;31(2):109. doi: 10.1007/s00520-022-07566-6.

  PMID: 36625831 DERIVED

• Burns MA, Place AE, Stevenson KE, Gutierrez A, Forrest S, Pikman Y, Vrooman LM, Harris MH, Hunt SK, O'Brien JE, Asselin BL, Athale UH, Clavell LA, Cole PD, Gennarini LM, Kahn JM, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Schorin MA, Sulis ML, Welch JJG, Neuberg DS, Sallan SE, Silverman LB. Identification of prognostic factors in childhood T-cell acute lymphoblastic leukemia: Results from DFCI ALL Consortium Protocols 05-001 and 11-001. Pediatr Blood Cancer. 2021 Jan;68(1):e28719. doi: 10.1002/pbc.28719. Epub 2020 Oct 7.

  PMID: 33026184 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

calaspargase pegol; pegaspargase

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Dr. Lewis Silverman
• Organization: Dana-Farber Cancer Institute

lewis_silverman@dfci.harvard.edu

16176326191

Study Officials

• Andrew Place, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 5, 2012
• First Posted: April 10, 2012
• Study Start: June 1, 2012
• Primary Completion: July 1, 2021
• Study Completion (Estimated): July 1, 2027
• Last Updated: February 5, 2026
• Results First Posted: September 10, 2022

Record last verified: 2026-01

Locations

CA (3); US (5)