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| ID | Type | Description | Link |
|---|---|---|---|
| CCG-09714 | |||
| CDR0000066850 | |||
| COG-09714 | Other Identifier | Children's Oncology Group |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Stratum 1 - Stage 1 | Experimental | 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. |
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| Stratum 2 - Stage 2 | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| topotecan hydrochloride | Drug | given by mouth |
|
| 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 |
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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
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| Name | Affiliation | Role |
|---|---|---|
| John S. Holcenberg, MD | Seattle Children's Hospital | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Long Beach Memorial Medical Center | Long Beach | California | 90806 | United States | ||
| Children's Hospital Los Angeles |
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| Los Angeles |
| California |
| 90027-0700 |
| United States |
| Jonsson Comprehensive Cancer Center, UCLA | Los Angeles | California | 90095-1781 | United States |
| Children's Hospital of Orange County | Orange | California | 92868 | United States |
| UCSF Cancer Center and Cancer Research Institute | San Francisco | California | 94115-0128 | United States |
| Children's Hospital of Denver | Denver | Colorado | 80218 | United States |
| Children's National Medical Center | Washington D.C. | District of Columbia | 20010-2970 | United States |
| University of Chicago Cancer Research Center | Chicago | Illinois | 60637 | United States |
| Indiana University Cancer Center | Indianapolis | Indiana | 46202-5265 | United States |
| University of Iowa Hospitals and Clinics | Iowa City | Iowa | 52242 | United States |
| University of Michigan Comprehensive Cancer Center | Ann Arbor | Michigan | 48109-0752 | United States |
| CCOP - Kalamazoo | Kalamazoo | Michigan | 49007-3731 | United States |
| Mayo Clinic Cancer Center | Rochester | Minnesota | 55905 | United States |
| Children's Mercy Hospital | Kansas City | Missouri | 64108 | United States |
| University of Nebraska Medical Center | Omaha | Nebraska | 68198-3330 | United States |
| Cancer Institute of New Jersey | New Brunswick | New Jersey | 08901 | United States |
| St. Joseph's Hospital and Medical Center | Paterson | New Jersey | 07503 | United States |
| NYU School of Medicine's Kaplan Comprehensive Cancer Center | New York | New York | 10016 | United States |
| Memorial Sloan-Kettering Cancer Center | New York | New York | 10021 | United States |
| Herbert Irving Comprehensive Cancer Center | New York | New York | 10032 | United States |
| Lineberger Comprehensive Cancer Center, UNC | Chapel Hill | North Carolina | 27599-7295 | United States |
| Veterans Affairs Medical Center - Fargo | Fargo | North Dakota | 58102 | United States |
| CCOP - Merit Care Hospital | Fargo | North Dakota | 58122 | United States |
| Children's Hospital Medical Center - Cincinnati | Cincinnati | Ohio | 45229-3039 | United States |
| Ireland Cancer Center | Cleveland | Ohio | 44106-5065 | United States |
| Children's Hospital of Columbus | Columbus | Ohio | 43205-2696 | United States |
| Doernbecher Children's Hospital | Portland | Oregon | 97201-3098 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania | 15213 | United States |
| Vanderbilt Cancer Center | Nashville | Tennessee | 37232-6838 | United States |
| University of Texas - MD Anderson Cancer Center | Houston | Texas | 77030-4009 | United States |
| Huntsman Cancer Institute | Salt Lake City | Utah | 84132 | United States |
| Children's Hospital and Regional Medical Center - Seattle | Seattle | Washington | 98105 | United States |
| Fred Hutchinson Cancer Research Center | Seattle | Washington | 98109 | United States |
| University of Wisconsin Comprehensive Cancer Center | Madison | Wisconsin | 53792 | United States |
| Princess Margaret Hospital for Children | Perth | Western Australia | 6001 | Australia |
| British Columbia Children's Hospital | Vancouver | British Columbia | V6H 3V4 | Canada |
| IWK Grace Health Centre | Halifax | Nova Scotia | B3J 3G9 | Canada |
| ID | Term |
|---|---|
| D007938 | Leukemia |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D001752 | Blast Crisis |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007945 | Leukemia, Lymphoid |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| D007951 | Leukemia, Myeloid |
| D002471 | Cell Transformation, Neoplastic |
| D063646 | Carcinogenesis |
| D009385 | Neoplastic Processes |
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D019772 | Topotecan |
| ID | Term |
|---|---|
| D002166 | Camptothecin |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
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