Study of IRNEA (Irinotecan, Etoposide, Cytarabine) for Refractory or Relapsed Acute Leukemia in Children and Adolescents

Phase I Study of IRNEA (Irinotecan, Etoposide, Cytarabine) for Refractory or Relapsed Acute Leukemia in Children and Adolescents

The purpose of this study is to determine the maximum tolerable dose of irinotecan in combination with etoposide, cytarabine for refractory or relapsed acute leukemia in pediatric patient.

Study Overview

• Status: Unknown
• Conditions: Acute Leukemia
• Intervention / Treatment: Drug: Irinotecan

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Chongno-gu
    • Seoul, Chongno-gu, Korea, Republic of, 110-744
      • Recruiting
      • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of ALL or AML.

• Prior therapy Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

  • ALL patients must have had two or more prior therapeutic attempts defined as

    • Persistent (BM blast>5%) initial disease after two induction attempts, or
    • Persistent (BM blast>5%) after re-induction attempt for first relapse or
    • Relapse after one re-induction attempt (2nd relapse)

  • AML patients must have one or more prior therapeutic attempts defined as

    • Refractory (BM blast>20%) initial disease after one induction attempts, or
    • Persistent (BM blast>5%) initial disease after two induction attempts, or
    • Relapse after one induction attempt (1st relapse)
  • Relapse after stem cell transplant: Patients are eligible 12 weeks after allogeneic stem cell transplant as long as patients are not actively being treated for GvHD and have recovered from transplant-related toxicities. Patients are eligible 8 weeks from the day of stem cell infusion for myeloablative autologous stem cell transplant, if hematological and all other eligibility criteria are met.
• Age: ≤ 21 years.
• Performance status: ECOG 0-2.

• Patients must be free of significant functional deficits in major organs, but the following eligibility criteria may be modified in individual cases.

  1. Heart: a shortening fraction ≥ 28%
  2. Liver: total bilirubin < 2 × upper limit of normal; ALT < 3 × upper limit of normal.
  3. Kidney: creatinine <2 × normal or a creatinine clearance (GFR) > 60 ml/min/1.73m2.
• Patients must lack any active viral infections or active fungal infection.
• Patients (or one of parents if patients age < 19) should sign informed

Exclusion Criteria:

1. Pregnant or nursing women.
2. Malignant (except acute leukemia) or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy.
3. Psychiatric disorder that would preclude compliance.
4. Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Irinotecan

Drug: Irinotecan; Chemotherapy: irinotecan, etoposide, and cytarabine daily for 5 days (on days 0, 1, 2, 3, & 4) -30 min: Atropin ivs 0 hour: irinotecan X mg/m2 in D5W 100 mL IV over 60 min 0 hour: etoposide 100 mg/m2 in x3 N/S mL IV over 60 min 12 hour: cytarabine 2,000 mg/m2 over 3 hr *if age ≤ 3 yrs: calculate all drugs in kg base (30kg=1m2) Irinotecan dose is escalated by 25-30% in successive cohorts. The starting irinotecan dose (level 1) is 20 mg/m2/dose on days 0 to 4.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the maximum tolerable dose of irinotecan in combination with etoposide, cytarabine for refractory or relapsed acute leukemia in pediatric patient.	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate the incidence and severity of toxicity and treatment related mortality. 2. To evaluate the response rate. 3. To determine the pharmacokinetic profile of irinotecan in combination with etoposide, cytarabine in pediatric patients.	2 years

Collaborators and Investigators

• Sponsor: Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (ANTICIPATED): December 1, 2013
• Study Completion (ANTICIPATED): December 1, 2013

Study Registration Dates

• First Submitted: November 8, 2010
• First Submitted That Met QC Criteria: November 10, 2010
• First Posted (ESTIMATE): November 11, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): November 19, 2013
• Last Update Submitted That Met QC Criteria: November 17, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Pediatric refractory or relapsed acute leukemia
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Leukemia; Acute Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: SCLSG-0901, SNUCH-RAL-0901