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

Purpose

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.

Condition	Intervention	Phase
Acute Leukemia	Drug: Irinotecan	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I Study of IRNEA (Irinotecan, Etoposide, Cytarabine) for Refractory or Relapsed Acute Leukemia in Children and Adolescents

Resource links provided by NLM:

MedlinePlus related topics: Leukemia

Drug Information available for: Cytarabine Etoposide Irinotecan Irinotecan hydrochloride Etoposide phosphate

U.S. FDA Resources

Further study details as provided by Seoul National University Hospital:

Primary Outcome Measures:

To determine the maximum tolerable dose of irinotecan in combination with etoposide, cytarabine for refractory or relapsed acute leukemia in pediatric patient. [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	18
Study Start Date:	November 2010
Estimated Study Completion Date:	December 2013
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Arms

Assigned Interventions

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.

Eligibility

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01239485

Contacts

Contact: Hyoung Jin Kang, M.D, Ph.D	82 2 2072 3304	kanghj@snu.ac.kr
Contact: Ji Won Lee, M.D	82 2 2072 0177	agnesjw@hanmail.net

Locations

Korea, Republic of
Seoul National University Hospital	Recruiting
Seoul, Chongno-gu, Korea, Republic of, 110-744
Contact: Hyoung Jin Kang, M.D, Ph.D 82 2 2072 3304 kanghj@snu.ac.kr

Sponsors and Collaborators

Seoul National University Hospital

Investigators

Principal Investigator:

Hyoung Jin Kang, M.D, ph.D

Seoul National University Hospital

More Information

No publications provided

Responsible Party:	Korea Childhood Leukemia Foundation
ClinicalTrials.gov Identifier:	NCT01239485 History of Changes
Other Study ID Numbers:	SCLSG-0901, SNUCH-RAL-0901
Study First Received:	November 8, 2010
Last Updated:	April 2, 2013
Health Authority:	Korea: Food and Drug Administration

Keywords provided by Seoul National University Hospital:

Pediatric refractory or relapsed acute leukemia

Additional relevant MeSH terms:

Leukemia
Acute Disease
Neoplasms by Histologic Type
Neoplasms
Disease Attributes
Pathologic Processes
Cytarabine
Etoposide phosphate
Irinotecan
Etoposide
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action

Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on May 22, 2013