Fludarabine/Carboplatin/Topotecan w/Thalidomide for Relapsed/Refractory AML, CML and MDS - Full Text View

Sponsor:	Case Comprehensive Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00053287

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Thalidomide may stop the growth of cancer cells by stopping blood flow to the tumor. Combining chemotherapy with thalidomide may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining fludarabine, carboplatin, and topotecan with thalidomide in treating patients who have relapsed or refractory acute myeloid leukemia, chronic myelogenous leukemia, or advanced myelodysplastic syndromes.

Condition	Intervention	Phase
Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Drug: carboplatin Drug: fludarabine phosphate Drug: thalidomide Drug: topotecan hydrochloride	Phase II

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase II Study of Fludarabine, Carboplatin, and Topotecan With Thalidomide for Patients With Relapsed/Refractory or High Risk Acute Myelogenous Leukemia, Chronic Myeloid Leukemia and Advanced Myelodysplastic Syndromes

Resource links provided by NLM:

Genetics Home Reference related topics: acute promyelocytic leukemia

MedlinePlus related topics: Acute Myeloid Leukemia Anemia Cancer Chronic Myeloid Leukemia Leukemia Myelodysplastic Syndromes

Drug Information available for: Thalidomide Fludarabine Carboplatin Fludarabine monophosphate Topotecan hydrochloride Topotecan

U.S. FDA Resources

Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:

Complete response rate [ Time Frame: 6 weeks after treatment ] [ Designated as safety issue: No ]

Enrollment:	42
Study Start Date:	September 2002
Study Completion Date:	March 2007
Primary Completion Date:	January 2007 (Final data collection date for primary outcome measure)

Intervention Details:

Carboplatin IV over 24 hours on days 1-5

Fludarabine IV over 5-10 minutes on days 1-5.

Oral thalidomide daily beginning within days 1-3 and continuing in the absence of disease progression or unacceptable toxicity.

Topotecan IV continuously over 72 hours.

Detailed Description:

OBJECTIVES:

Determine the response rate of patients with relapsed/refractory or high-risk acute myeloid leukemia, chronic myelogenous leukemia, or advanced myelodysplastic syndromes treated with fludarabine, carboplatin, topotecan, and thalidomide.
Determine the non-hematologic toxicity profile and time to hematopoietic recovery in patients treated with this regimen.
Determine the effects of this regimen on changes in biologic parameters that may predict response in these patients.
Correlate bone marrow microvascular density before and after treatment with response in these patients.
Determine the prognostic value of pretreatment plasma and serum levels of vascular endothelial growth factor (VEGF) and/or the modulation of serum levels of VEGF during treatment in predicting response in these patients.

OUTLINE: Patients are stratified according to diagnosis (previously untreated acute leukemia vs other).

Patients receive fludarabine IV over 5-10 minutes and carboplatin IV over 24 hours on days 1-5 followed by topotecan IV continuously over 72 hours. Patients receive oral thalidomide daily beginning within days 1-3 and continuing in the absence of disease progression or unacceptable toxicity.

Patients with residual disease on day 16-18 may receive a second course of chemotherapy as above. Patients who achieve remission may receive a third course of chemotherapy as above as consolidation beginning 4-8 weeks after completion of prior chemotherapy.

Patients are followed monthly for 6 months.

PROJECTED ACCRUAL: A total of 40 patients (20 per stratum) will be accrued for this study.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following:
- Acute myeloid leukemia meeting 1 of the following criteria:
  - Previously untreated and not a candidate for anthracycline-based chemotherapy
  - In first or second relapse or refractory
  - Secondary to chemotherapy or an antecedent hematologic disorder and treated with no more than 1 prior intensive induction regimen
- Chronic myelogenous leukemia in blast crisis at diagnosis or after prior imatinib mesylate
- Myelodysplastic syndromes (MDS)
  - Refractory anemia with excess blasts (RAEB) or RAEB in transformation
  - Must meet at least 1 of the following criteria:
    - Absolute neutrophil count no greater than 500/mm^3
    - Platelet or red cell transfusion-dependent after no more than 1 prior intensive induction chemotherapy
- Acute promyelocytic leukemia
  - t(15, 17)
  - Failed prior treatment with tretinoin and arsenic
- Relapsed disease at least 3 months after prior autologous stem cell transplantation
No active CNS leukemia

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-3

Life expectancy

At least 8 weeks

Hematopoietic

See Disease Characteristics

Hepatic

Bilirubin no greater than 2.0 mg/dL
AST and ALT less than 3 times upper limit of normal

Renal

Creatinine clearance at least 50 mL/min

Cardiovascular

Ejection fraction at least 40%
No poorly controlled cardiac disease

Pulmonary

No poorly controlled pulmonary disease

Other

Not pregnant or nursing
Negative pregnancy test
Fertile female patients must use 1 highly effective and 1 additional method of contraception for 4 weeks before, during, and for at least 4 weeks after study
Male patients must use effective contraception during and for 4 weeks after study
Willing and able to comply with the System for Thalidomide Education and Prescribing Safety (STEPS) program
HIV negative
No poorly controlled infection
No other active malignancy
No severe peripheral neuropathy

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Disease Characteristics
Prior thalidomide allowed for MDS
At least 5 days since prior hematopoietic growth factors
At least 2 weeks since prior biologic therapy
No prior allogeneic bone marrow transplantation

Chemotherapy

See Disease Characteristics
At least 24 hours since prior hydroxyurea

Endocrine therapy

At least 24 hours since prior corticosteroids

Radiotherapy

Not specified

Surgery

Not specified

Other

At least 2 weeks since prior cytotoxic anticancer therapy
Prior amifostine allowed for MDS

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00053287

Locations

United States, Ohio
Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065

Sponsors and Collaborators

Case Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Brenda W. Cooper, MD

Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

More Information

Additional Information:

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

No publications provided

Responsible Party:	Brenda Cooper, MD, Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00053287 History of Changes
Other Study ID Numbers:	CWRU1902, P30CA043703, CASE-CWRU-1902, CELGENE-CWRU-1902, CASE-1902
Study First Received:	January 27, 2003
Last Updated:	June 9, 2010
Health Authority:	United States: Federal Government

Keywords provided by Case Comprehensive Cancer Center:

adult acute promyelocytic leukemia (M3)
refractory anemia with excess blasts in transformation
refractory anemia with excess blasts
de novo myelodysplastic syndromes
recurrent adult acute myeloid leukemia
secondary acute myeloid leukemia
untreated adult acute myeloid leukemia
blastic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia

previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
atypical chronic myeloid leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with t(15;17)(q22;q12)

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Thalidomide
Fludarabine monophosphate

Vidarabine
Fludarabine
Carboplatin
Topotecan
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances

ClinicalTrials.gov processed this record on February 13, 2012