Combination Chemotherapy in Treating Patients With Chronic Myelogenous Leukemia or Recurrent Acute Leukemia - Full Text View

Sponsor:	Mayo Clinic
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00002693

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy with carboplatin and topotecan in treating patients with chronic myelogenous leukemia or recurrent acute leukemia.

Condition	Intervention	Phase
Leukemia Neutropenia	Biological: filgrastim Drug: carboplatin Drug: topotecan hydrochloride	Phase I

Study Type:	Interventional
Study Design:	Treatment
Official Title:	PHASE I STUDY OF CONTINUOUS INFUSION CARBOPLATIN AND TOPOTECAN IN THE TREATMENT OF RELAPSED ACUTE LEUKEMIA AND BLAST CRISIS CHRONIC MYELOGENOUS LEUKEMIA

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Carboplatin Topotecan hydrochloride Filgrastim Topotecan

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

October 1995

Detailed Description:

OBJECTIVES:

Estimate the maximum tolerated dose of carboplatin plus topotecan given as a 5-day continuous infusion in patients with recurrent acute lymphocytic or myeloid leukemia or accelerated or blastic phase chronic myelogenous leukemia.
Assess the toxicity of this regimen in these patients.
Gather preliminary information on the activity of this regimen in these patients.
Examine the pharmacokinetics of topotecan when administered concurrently with carboplatin.

OUTLINE: This is a dose escalation study of topotecan. Patients are stratified according to prior bone marrow transplant (BMT) (yes vs no).

Induction: Patients receive carboplatin and topotecan IV 3 times a day on days 1-5. Patients may also receive filgrastim (G-CSF) beginning on day 7 or 14. Retreatment is based on results of marrow exam on day 10-14. Patients with less than 5% blasts undergo a second marrow exam upon blood count recovery or on day 26-30, whichever is earlier. Patients with at least 5% blasts after day 21 receive one more course, in the absence of unacceptable toxicity and at the discretion of the investigator. Patients with no greater than 5% blasts begin G-CSF if blood counts are not recovered, then proceed to consolidation.

Cohorts of 1-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of up to 6 patients experience dose limiting toxicity. Patients with prior BMT will not be entered at any level until 3-6 patients with no prior BMT tolerate that level.

Consolidation (begins around day 42 of last Induction course): Patients with ALL/AML in complete remission (CR) or CML in chronic phase receive 2 additional courses (same doses) 6-8 weeks apart.

Patients experiencing a relapse after CR lasting at least 6 months may receive additional treatment.

PROJECTED ACCRUAL: A total of 15-20 patients without and 2-20 patients with prior bone marrow transfer will be accrued for this study over 2-2.5 years.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Acute lymphocytic or myeloid leukemia (ALL or AML) in 1 of the following categories:
- Failed to achieve a complete response (CR) with initial induction regimen
- First relapse within 1 year of initial CR
- Failed re-induction therapy at first relapse
- Second relapse after no more than 2 different induction regimens
- Relapse defined as more than 10% blasts in marrow or circulating blasts in peripheral blood and either:
  - Symptoms of recurrence (e.g., B symptoms)
  - Evidence of impending marrow failure (i.e., cytopenias) OR
Chronic myelogenous leukemia in accelerated or blastic phase after no more than 1 prior induction regimen
No HLA-identical sibling marrow donor or patient ineligible for allogeneic marrow transplantation
No clinical symptoms of CNS leukemia
- Patients with history of CNS leukemia must have pretreatment lumbar puncture demonstrating absence of active CNS disease
No active CNS disease

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-2

Life expectancy:

At least 4 weeks

Hematologic:

Not applicable

Hepatic:

Bilirubin less than 2 mg/dL

Renal:

Creatinine no greater than 1.5 mg/dL

Cardiovascular:

No congestive heart failure
No poorly controlled arrhythmia
No myocardial infarction within the past 3 months

Other:

No active infection
No other serious medical condition that would prevent compliance
Not pregnant or nursing
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

See Disease Characteristics

Chemotherapy:

See Disease Characteristics
At least 24 hours since prior hydroxyurea for impending leukostasis
No concurrent hydroxyurea glucocorticoids
Recovered from prior chemotherapy

Endocrine therapy:

At least 24 hours since prior glucocorticoids for impending leukostasis
At least 7 days since prior amphotericin or aminoglycosides
No concurrent glucocorticoids

Radiotherapy:

Not specified

Surgery:

Not specified

Other:

No concurrent aminoglycoside antibiotics

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002693

Locations

United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

Study Chair:

Scott H. Kaufmann, MD, PhD

Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Kaufmann S, Letendre L, Litzow M, et al.: Phase I study of continuous infusion (CI) topotecan (TPT) and carboplatin (CBDCA) for relapsed or refractory acute leukemia. [Abstract] Proceedings of the American Society of Clinical Oncology 17: A107, 1998.

Study ID Numbers:	CDR0000064447, MAYO-958101, NCI-T95-0050H
Study First Received:	November 1, 1999
Last Updated:	May 9, 2009
ClinicalTrials.gov Identifier:	NCT00002693 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia

accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
neutropenia

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Hematologic Diseases
Myeloproliferative Disorders
Agranulocytosis
Enzyme Inhibitors
Leukocyte Disorders
Leukemia, Myeloid
Carboplatin

Pharmacologic Actions
Leukemia
Neutropenia
Neoplasms
Therapeutic Uses
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Topotecan
Bone Marrow Diseases
Leukopenia

ClinicalTrials.gov processed this record on November 27, 2009