Erwinase for Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) (IND 104224)

NCT00928200 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: T2006-002
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I study using the Erwinia form of asparaginase in place of the E. coli form using a standard re-induction regimen (Vincristine, Dexamethasone, Doxorubicin) for patients with relapsed ALL who have developed an allergy to the E. coli formulation. This study will administer the drug intravenously instead of the usual intramuscular route. The dose of Erwinia will be escalated in the absence of dose limiting toxicity. Patients must have first or second relapse ALL with a history of prior systemic reaction to E. coli asparaginase.

Conditions

Relapsed Acute Lymphoblastic Leukemia; Allergy to PEG e.Coli Asparaginase; Allergy to Native e.Coli Asparaginase

Keywords

Relapsed; Allergy; Erwinia; Acute; Lymphoblastic; Leukemia

Outcome Measures

Primary Outcomes (1)

• Occurrence of a Dose-Limiting Toxicity

  The MTD in each stratum will be the highest dose at which 1 or fewer of six patients experience DLT during cycle 1 of therapy.

  Beginning with the first dose of investigational product until 30 days following the last dose of Erwinase

Secondary Outcomes (2)

• Response Rate and Minimum Residual Disease

  After completion of treatment course

• Asparaginase Activity

  PK samples to be collected Pre-Tx, and and Erwinase Doses 3, 6 and 9 and Day 29

Study Arms (1)

Single Arm

EXPERIMENTAL

All patients receive Vincristine, Dexamethasone, Doxorubicin, and Cytarabine. Dexrazoxane optional on Day 1. Erwinase is started between Days 3-5 and is given every M-W-F for a total of 10 doses. Patients with CNS 1 or 2 receive Methotrexate intrathecally on Day 15. Patients with CNS 3 receive Triple Intrathecal Therapy (Methotrexate, Cytarabine and Hydrocortisone) on Days 8, 15, and 22.

Drug: Erwinase; Drug: Vincristine; Drug: Dexamethasone; Drug: Doxorubicin; Drug: Cytarabine; Drug: Methotrexate; Drug: Triple Intrathecal Therapy; Drug: Dexrazoxane

Interventions

Erwinase DRUG

The dose of Erwinase will be assigned at study entry. The first dose of Erwinase wil be given between Days 3-5 and will continue on a M-W-F schedule for a total of 10 doses. Erwinase will be administered as a 2-hour intravenous infusion.

Also known as: Asparaginase, Elspar, Kidrolase, L-Asparaginase, Erwinia L-Asparaginase

Single Arm

Vincristine DRUG

1.5 mg/m2/dose IV push (maximum single dose 2 mg) on Days 1, 8, 15 and 22

Also known as: Oncovin, Vincasar Pfs, Vincristine Sulfate, LCR, VCR

Single Arm

Dexamethasone DRUG

10 mg/m2/day divided BID. Give by mouth days 1-14.

Also known as: Decadron, Dexasone, Diodex, Hexadrol, Maxidex, Dexamethasone sodium phosphate, Dexamethasone acetate

Single Arm

Doxorubicin DRUG

60 mg/m2/day IV over 15 minutes on day 1

Also known as: Adriamycin, Rubex

Single Arm

Cytarabine DRUG

Given Intrathecally at the dose defined by age on day 1. 30 mg for age 1-1.99 50 mg for age 2-2.99 70 mg for age 3 and older

Also known as: Cytosar-U, Ara-C, Arabinosylcytosine

Single Arm

Methotrexate DRUG

Given Intrathecally to all patients who are CNS 1 or 2 at study entry. Dose defined by age. Given on day 15 8mg for age 1-1.99 10 mg for age 2-2.99 12 mg for age 3-8.99 15 mg for age 9 and older

Also known as: Otrexup, Rasuvo, Rheumatrex, Trexall, Amethopterin, Methotrexate Sodium, MTX

Single Arm

Triple Intrathecal Therapy DRUG

Methotrexate, Cytarabine and Hydrocortisone given Intrathecally on day 8, 15 and 22 for patients who are CNS 3 at study entry. Doses determined by age.

Single Arm

Dexrazoxane DRUG

Due to the limited availability of Dexrazoxane (Zinecard®), treatment will be at the discretion of the treating physician. Dose should be 600 mg/m2 as a IV push immediately prior to anthracycline dose (the elapsed time from the beginning of the dexrazoxane dose to the end of the anthracycline infusion should be 30 minutes or less).

Also known as: Zinecard

Single Arm

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age Patients must be \>1 and \< 21 years of age when enrolled onto this study.
• Diagnosis Patients must have relapsed or refractory ALL with a M3 marrow (marrow blasts \>25%) who have had no more than two prior therapeutic attempts. Patients with CNS 1, 2, or 3 or testicular disease are eligible. (See section 11.3 for CNS definitions)
• E. coli Asparaginase Allergy Patients must have a history of prior systemic allergic reaction to E. coli asparaginase (native or pegylated), such as urticaria, wheezing, or anaphylaxis. Local reactions are not sufficient.
• Performance Level Karnofsky \> 50% for patients \> 10 years of age and Lansky \> 50% for patients \< 10 years of age.
• Prior Therapy Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
• Patients may be in first or second relapse and should not have received more than 2 induction attempts (including frontline therapy).
• Prior anthracycline exposure: Patients must have less than 400mg/m2 lifetime exposure of anthracycline chemotherapy.
• Stem Cell Transplant (SCT): Patients are eligible after allogeneic stem cell transplant as long as patients are not actively being treated for graft-versus-host-disease (GvHD).
• Patients may have received previous therapy using intramuscular (IM) Erwinase. Patients who have received Erwinase intravenously will be excluded.
• Reproductive Function
• Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed prior to enrollment.
• Female patients with infants must agree not to breastfeed their infants while on this study.
• Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study.

You may not qualify if:

• Prior Stroke Patients with a prior history of asparaginase associated stroke are excluded. Patients with a history of other asparaginase related deep-venous thromboses (including intra-cranial thromboses without evidence of stroke or hemorrhage) are eligible.
• Down Syndrome Patients with Down Syndrome will be excluded.
• Prior Pancreatitis Patients with prior history of Grade 2 or greater asparaginase-induced symptomatic pancreatitis will be excluded.
• Renal Function Patients will be excluded if their serum creatinine is \> 1.5 x the upper limit of normal for age at the institution's laboratory.
• Liver/Pancreatic Function
• Patients will be excluded if their lab results are as follows:
• Direct bilirubin \> 1.5x the institutional ULN for age. A total bilirubin result that is less than 1.5 times the institutional ULN for age may be used for eligibility if a direct bilirubin result is not available.
• SGPT (ALT) \> 4 x institutional ULN
• Amylase or Lipase \> 2 x institutional ULN
• Cardiac Function Patients will be excluded if their shortening fraction by echocardiogram is less than the institutional normal for age or an ejection fraction by MUGA is less than the institutional normal for age.
• Infection Patients will be excluded if they have an active uncontrolled infection.
• Patients planning on receiving other investigational agents while on this study. (An investigational agent is defined as any drug not currently approved for use in humans.)
• Patients planning on receiving other anti-cancer therapies while on this study.
• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
• Patients who have started protocol therapy prior to enrollment. Patient may still enroll if IT therapy was given within 72 hours of study enrollment as part of the diagnostic lumbar procedure.

Sponsors & Collaborators

• Therapeutic Advances in Childhood Leukemia Consortium: lead

Study Sites (1)

Childrens Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Related Links

• Therapeutic Advances in Childhood Leukemia \& Lymphoma Consortium web site

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Hypersensitivity; Leukemia

Interventions

Asparaginase; asparaginase erwinia chrysanthemi recombinant; Vincristine; Dexamethasone; Calcium Dobesilate; dexamethasone 21-phosphate; dexamethasone acetate; Doxorubicin; Cytarabine; Methotrexate; Dexrazoxane

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Aminopterin; Pterins; Pteridines; Razoxane; Diketopiperazines; Piperazines

Limitations and Caveats

The study closed early due to lack of accrual and insufficient funding. Only one patient was enrolled. This patient completed the protocol therapy.

Results Point of Contact

• Title: Peggy Romano, BA, CCRP
• Organization: Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) / Children's Hospital Los Angeles

promano@chla.usc.edu

323-361-5505

Study Officials

• Heather Grossman, MD

  Children's Hopital New York

  STUDY CHAIR

• Paul Gaynon, MD

  Children's Hospital Los Angeles

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2009
• First Posted: June 25, 2009
• Study Start: April 13, 2009
• Primary Completion: June 4, 2010
• Study Completion: June 4, 2010
• Last Updated: February 19, 2019
• Results First Posted: February 19, 2019

Record last verified: 2018-07

Locations

US (1)