High-Intensity, Brief-Duration Chemotherapy in Treating Patients With Relapsed or Refractory Acute Lymphocytic Leukemia

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of high-intensity, brief-duration chemotherapy in treating patients with relapsed or refractory acute lymphocytic leukemia.

Detailed Description
-----------------
OBJECTIVES: I. Determine the complete response rate to high-intensity, brief-duration chemotherapy with cyclophosphamide, methotrexate, vincristine, doxorubicin, and dexamethasone followed by ifosfamide, methotrexate, vincristine, cytarabine, etoposide, and dexamethasone in patients with relapsed or refractory acute lymphocytic leukemia (ALL). II. Determine the toxic effects of these regimens in these patients. OUTLINE: All patients receive up to six alternating courses (every 3-4 weeks) of two chemotherapy regimens: cyclophosphamide, oral dexamethasone, methotrexate with leucovorin rescue, vincristine, and doxorubicin over 5 days; and ifosfamide/mesna, oral dexamethasone, methotrexate with leucovorin rescue, vincristine, cytarabine, and etoposide over 5 days. G-CSF is given following each course until recovery of the neutrophil count. All patients receive triple intrathecal chemotherapy on day 1. Patients with CNS disease receive intrathecal therapy twice weekly until the CSF is clear, then weekly for 4 weeks, and monthly for 1 year; those who have not received prior CNS irradiation also receive whole-brain radiotherapy. Patients are followed monthly for 6 months, every 3 months for 18 months, every 6 months for 2 years, then annually. PROJECTED ACCRUAL: A total of 37 evaluable patients will be accrued if at least 4 of the first 17 patients respond.

Official Title
-----------------
HIGH INTENSITY, BRIEF DURATION CHEMOTHERAPY FOR RELAPSED OR REFRACTORY ALL: A PHASE II STUDY OF A MULTIDRUG REGIMEN

Conditions
-----------------
Leukemia

Intervention / Treatment
-----------------
* Biological: filgrastim
* Drug: cyclophosphamide
* Drug: cytarabine
* Drug: dexamethasone
* Drug: doxorubicin hydrochloride
* Drug: etoposide
* Drug: ifosfamide
* Drug: leucovorin calcium
* Drug: mesna
* Drug: methotrexate
* Drug: therapeutic hydrocortisone
* Drug: vincristine sulfate
* Radiation: low-LET cobalt-60 gamma ray therapy
* Radiation: low-LET photon therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed acute lymphocytic leukemia that is relapsed after or refractory to induction therapy 1 or 2 prior inductions allowed, but refractory to only 1 regimen CNS involvement allowed PATIENT CHARACTERISTICS: Age: 18 and over Performance status: 0-3 Hematopoietic: Not specified Hepatic: Bilirubin no greater than 1.5 times normal (unless directly attributable to leukemia) Renal: Creatinine no greater than 1.5 times normal (unless directly attributable to leukemia) Cardiovascular: No uncontrolled or severe cardiovascular disease including: Myocardial infarction within 6 months Congestive heart failure Other: No uncontrolled duodenal ulcer No uncontrolled infection No second malignancy within 5 years except curatively treated: In situ cervical cancer Basal cell skin cancer No other serious medical illness that would limit survival to under 2 years No psychiatric illness that would prevent informed consent or compliance No pregnant or nursing women Adequate contraception required of fertile patients PRIOR CONCURRENT THERAPY: See Disease Characteristics

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: filgrastim|nan|
|Drug: cyclophosphamide|nan|
|Drug: cytarabine|nan|
|Drug: dexamethasone|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: etoposide|nan|
|Drug: ifosfamide|nan|
|Drug: leucovorin calcium|nan|
|Drug: mesna|nan|
|Drug: methotrexate|nan|
|Drug: therapeutic hydrocortisone|nan|
|Drug: vincristine sulfate|nan|
|Radiation: low-LET cobalt-60 gamma ray therapy|nan|
|Radiation: low-LET photon therapy|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response rate for patients with relapsed or refractory acute lymphoblastic leukemia after brief, high intensity chemotherapy |  | 14 days | 
| evaluate adverse events after brief, high intensity chemotherapy |  | 28 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
recurrent adult acute lymphoblastic leukemia