Combination Chemotherapy in Treating Young Patients With Relapsed or Refractory Acute Leukemia - Full Text View

Sponsors and Collaborators:	Memorial Sloan-Kettering Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00462787

Purpose

RATIONALE: Drugs used in chemotherapy, such as clofarabine, topotecan, vinorelbine, thiotepa, and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of clofarabine when given together with topotecan, vinorelbine, thiotepa, and dexamethasone in treating young patients with relapsed or refractory acute leukemia.

Condition	Intervention	Phase
Leukemia	Drug: clofarabine Drug: dexamethasone Drug: filgrastim Drug: thiotepa Drug: topotecan hydrochloride Drug: vinorelbine ditartrate	Phase I

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

Drug Information available for: Filgrastim Dexamethasone Dexamethasone acetate Dexamethasone Sodium Phosphate Doxiproct plus Vinorelbine Vinorelbine tartrate Thiotepa Topotecan hydrochloride Topotecan Clofarabine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized
Official Title:	A Phase I Dose Escalation Trial of Clofarabine in Addition to Topotecan, Vinorelbine, Thiotepa, and Dexamethasone in Pediatric Patients With Relapsed or Refractory Acute Leukemia

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

Primary Outcome Measures:

Maximum tolerated dose of clofarabine [ Designated as safety issue: Yes ]
Overall survival [ Designated as safety issue: No ]
Progression-free survival [ Designated as safety issue: No ]

Estimated Enrollment:	18
Study Start Date:	April 2007
Estimated Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose of clofarabine when administered in combination with topotecan hydrochloride, vinorelbine ditartrate, thiotepa, and dexamethasone in young patients with relapsed or refractory acute leukemia.
Evaluate the antileukemic potential of this regimen in these patients.
Evaluate the incidence and severity of treatment-related morbidity and mortality in patients treated with this regimen.
Develop a new reinduction treatment regimen that will result in a patient clinical response with as little residual disease as possible to permit a bone marrow transplantation while in subsequent remission; maintain the response long enough to identify an appropriate stem cell donor; and permit the patient to undergo a stem cell transplantation free of infections and without vital organ dysfunction.

OUTLINE: This is a nonrandomized, prospective, dose-escalation study of clofarabine.

Patients receive topotecan hydrochloride IV continuously over 120 hours on days 0-4; vinorelbine ditartrate over 6-10 minutes on days 0, 7, and 14; thiotepa IV over 4 hours on day 2; clofarabine IV over 2 hours on days 3-7; and oral or IV dexamethasone 3 times daily on days 3 and 7-13. Patients also receive filgrastim (G-CSF) subcutaneously once daily beginning on day 8 and continuing until blood counts recover. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of clofarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose-limiting toxicity OR the dose preceding that at which 2 of 3 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

After completion of study treatment, patients are followed once a week for 4 weeks, twice a month for 6 months, and then once a month for 2 years.

PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	up to 20 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Must have 1 of the following diagnoses:
- Acute lymphoblastic leukemia (ALL) meeting 1 of the following criteria:
  - Refractory to initial induction with two or more standard regimens
  - Relapsed < 24 months after first complete response on a high-risk protocol OR refractory to one standard reinduction regimen
  - Second or greater relapse
- Acute myeloid leukemia, acute biphenotypic leukemia, or acute undifferentiated leukemia meeting 1 of the following criteria:
  - Refractory to initial induction
  - First or greater relapse
Must have > 20% bone marrow blasts, or evidence of recurrent disease at an extramedullary site
No symptomatic CNS disease
- Patients with asymptomatic CNS disease are eligible with the approval of the principal investigator

PATIENT CHARACTERISTICS:

Karnofsky performance status (PS) 70-100% OR Lansky PS 70-100%
AST and ALT < 4 times upper limit of normal
Bilirubin < 2.0 mg/dL (unless liver involvement)
Creatinine within normal range for age OR creatinine clearance > 60 mL/min/1.73 m^2
Adequate cardiac function (either asymptomatic with no prior risk factors, or if symptomatic, left ventricular ejection fraction > 50% at rest)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No active uncontrolled viral, bacterial, or fungal infection

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior clofarabine
More than 2 weeks since prior systemic chemotherapy
- At least 7 days since prior chemotherapy for patients with rapidly progressive disease and recovered

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00462787

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center	Recruiting
New York, New York, United States, 10021
Contact: Peter G. Steinherz, MD 212-639-7951

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Peter G. Steinherz, MD	Memorial Sloan-Kettering Cancer Center
Principal Investigator:	Neerav Shukla, MD	Memorial Sloan-Kettering Cancer Center

More Information

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

Study ID Numbers:	CDR0000539465, MSKCC-07012
Study First Received:	April 18, 2007
Last Updated:	January 15, 2009
ClinicalTrials.gov Identifier:	NCT00462787
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

acute undifferentiated leukemia
recurrent childhood acute lymphoblastic leukemia
recurrent childhood acute myeloid leukemia

Study placed in the following topic categories:

Dexamethasone
Clofarabine
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Acute myelogenous leukemia
Vinblastine
Leukemia, Myeloid
Leukemia, Myeloid, Acute

Recurrence
Thiotepa
Leukemia
Vinorelbine
Topotecan
Acute myelocytic leukemia
Dexamethasone acetate

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Hormones
Therapeutic Uses
Alkylating Agents
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Mitosis Modulators
Gastrointestinal Agents

Enzyme Inhibitors
Antimitotic Agents
Glucocorticoids
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Autonomic Agents
Tubulin Modulators
Myeloablative Agonists
Peripheral Nervous System Agents
Antineoplastic Agents, Alkylating
Central Nervous System Agents
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on January 16, 2009