Chemotherapy in Treating Children With Relapsed Acute Leukemia, Acute Myeloid Leukemia, or Blastic Phase Chronic Myelogenous Leukemia

A Phase II Study of Oral Topotecan in Children With Relapsed Acute Leukemia

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of topotecan in treating children who have relapsed acute leukemia, acute myeloid leukemia, or blast phase chronic myelogenous leukemia.

Study Overview

• Status: Completed
• Conditions: Leukemia
• Intervention / Treatment: Drug: topotecan hydrochloride

Detailed Description

OBJECTIVES: I. Determine the response rate of patients with relapsed acute lymphocytic leukemia, acute myeloid leukemia, or blastic phase chronic myelogenous leukemia treated with oral topotecan. II. Determine the toxic effects and pharmacokinetics of this regimen in these patients.

OUTLINE: Patients are stratified by disease type (acute lymphocytic leukemia vs acute myeloid leukemia). Patients receive oral topotecan once daily on days 1-21. Courses repeat every 28 days in the absence of blasts in the blood, M3 bone marrow, or unacceptable toxicity. Patients are followed every 6 months until death.

PROJECTED ACCRUAL: A total of 50 patients (25 per stratum) will be accrued for this study within 2 years.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Perth, Western Australia, Australia, 6001
      • Princess Margaret Hospital for Children
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • British Columbia Children's Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3J 3G9
      • IWK Grace Health Centre
• United States
  • California
    • Long Beach, California, United States, 90806
      • Long Beach Memorial Medical Center
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center, UCLA
    • Los Angeles, California, United States, 90027-0700
      • Children's Hospital Los Angeles
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • San Francisco, California, United States, 94115-0128
      • UCSF Cancer Center and Cancer Research Institute
  • Colorado
    • Denver, Colorado, United States, 80218
      • Children's Hospital of Denver
  • District of Columbia
    • Washington, District of Columbia, United States, 20010-2970
      • Children's National Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Cancer Research Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5265
      • Indiana University Cancer Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0752
      • University of Michigan Comprehensive Cancer Center
    • Kalamazoo, Michigan, United States, 49007-3731
      • CCOP - Kalamazoo
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198-3330
      • University of Nebraska Medical Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Cancer Institute Of New Jersey
    • Paterson, New Jersey, United States, 07503
      • St. Joseph's Hospital and Medical Center
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10016
      • NYU School of Medicine's Kaplan Comprehensive Cancer Center
    • New York, New York, United States, 10032
      • Herbert Irving Comprehensive Cancer Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7295
      • Lineberger Comprehensive Cancer Center, UNC
  • North Dakota
    • Fargo, North Dakota, United States, 58102
      • Veterans Affairs Medical Center - Fargo
    • Fargo, North Dakota, United States, 58122
      • CCOP - Merit Care Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45229-3039
      • Children's Hospital Medical Center - Cincinnati
    • Cleveland, Ohio, United States, 44106-5065
      • Ireland Cancer Center
    • Columbus, Ohio, United States, 43205-2696
      • Children's Hospital of Columbus
  • Oregon
    • Portland, Oregon, United States, 97201-3098
      • Doernbecher Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15213
      • Children's Hospital of Pittsburgh
  • Tennessee
    • Nashville, Tennessee, United States, 37232-6838
      • Vanderbilt Cancer Center
  • Texas
    • Houston, Texas, United States, 77030-4009
      • University of Texas - MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Huntsman Cancer Institute
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98105
      • Children's Hospital and Regional Medical Center - Seattle
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

DISEASE CHARACTERISTICS: Histologically proven relapsed acute lymphocytic leukemia, acute myeloid leukemia, or blastic phase chronic myelogenous leukemia Refractory to conventional therapy and other therapies of higher priority May have concurrent extramedullary relapse except for testicular relapse or other extramedullary sites that may require concurrent radiotherapy

PATIENT CHARACTERISTICS: Age: 21 and under Performance status: ECOG 0-2 Life expectancy: At least 2 months Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2.0 times normal SGOT or SGPT less than 5 times normal Renal: Creatinine no greater than 1.5 times normal Other: Able to take oral liquid medication No GI neuropathy No other condition that may affect absorption of drug No diabetes mellitus Not pregnant or nursing Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: Prior bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT) allowed and recovered At least 2 weeks since prior cytokine therapy and recovered No concurrent immune modulator therapy No concurrent cytokines including interleukin-11, interleukin-2, and epoetin alfa Chemotherapy: At least 2 weeks since prior chemotherapy (4 weeks for nitrosoureas) and recovered No more than 3 prior chemotherapy regimens No other concurrent chemotherapy Endocrine therapy: No concurrent steroids Radiotherapy: No prior craniospinal radiotherapy Prior total body irradiation allowed as part of BMT or PBSCT and recovered Concurrent radiotherapy for localized painful lesions allowed Surgery: Not specified Other: No concurrent metoclopramide or cisapride to maintain motility or gastric emptying No concurrent H2 antagonists No concurrent proton pump inhibitors No concurrent antacids for gastritis, gastroesophageal reflux, or ulcers (gastric or duodenal) No antacid therapy for 6 hours before and for 90 minutes after topotecan administration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stratum 1 - Stage 1; Topotecan hydrochloride (0.8 mg/m²/day) by mouth for 21 days. Bone marrow will be obtained on approximately Day 28 of Course 1 and 2 and in any course where the CBC suggests that a relapse has occurred. One additional course may be given if the blood is cleared of blasts and the bone marrow is M1, M2 or M3. The patient is off protocol therapy if blasts are still present in the blood and the marrow is M3. Subsequent courses of topotecan may be given only if the bone marrow after Course 2 is M1 or M2. If the bone marrow is M2 on Day 28 of any course, another bone marrow aspirate will be done at the end of the next course. If the patient is in CR, a bone marrow aspirate will be required only every other course unless the peripheral blood suggests that a relapse has occurred. Each subsequent course should begin within six weeks of the start of the previous course.	Drug: topotecan hydrochloride; given by mouth; Other Names: Hycamptamine; SK&B 104864-A; 9-dimethylaminomethyl-10-hydroxycamptothecin hydrochloride; IND #56, 270.
Experimental: Stratum 2 - Stage 2; Topotecan hydrochloride (0.8 mg/m²/day) by mouth for 21 days. Bone marrow will be obtained on approximately Day 28 of Course 1 and 2 and in any course where the CBC suggests that a relapse has occurred. One additional course may be given if the blood is cleared of blasts and the bone marrow is M1, M2 or M3. The patient is off protocol therapy if blasts are still present in the blood and the marrow is M3. Subsequent courses of topotecan may be given only if the bone marrow after Course 2 is M1 or M2. If the bone marrow is M2 on Day 28 of any course, another bone marrow aspirate will be done at the end of the next course. If the patient is in CR, a bone marrow aspirate will be required only every other course unless the peripheral blood suggests that a relapse has occurred. Each subsequent course should begin within six weeks of the start of the previous course.	Drug: topotecan hydrochloride; given by mouth; Other Names: Hycamptamine; SK&B 104864-A; 9-dimethylaminomethyl-10-hydroxycamptothecin hydrochloride; IND #56, 270.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Progression	For each stratum, this trial will determine topotecan to have insufficient activity for further investigation with probability 0.10 if the true response rate is 20%. For each stratum, this trial will determine topotecan to be of sufficient activity to warrant further investigation with probability 0.12 if the true response rate is 5%. Any patient who receives at least 21 days of therapy will be considered evaluable for response.	21 days

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: John S. Holcenberg, MD, Seattle Children's Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 1998
• Primary Completion (Actual): November 1, 2002
• Study Completion (Actual): September 1, 2006

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: April 22, 2004
• First Posted (Estimate): April 23, 2004

Study Record Updates

• Last Update Posted (Estimate): July 24, 2014
• Last Update Submitted That Met QC Criteria: July 23, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: blastic phase chronic myelogenous leukemia; recurrent childhood acute lymphoblastic leukemia; recurrent childhood acute myeloid leukemia
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Neoplastic Processes; Cell Transformation, Neoplastic; Carcinogenesis; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia; Blast Crisis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Topotecan; 10-hydroxycamptothecin
• Other Study ID Numbers: 09714; CCG-09714; CDR0000066850; COG-09714 (Other Identifier: Children's Oncology Group)