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Study Summary
No. 2005-0758:.......Leukemia; Pediatrics......Michael E. Rytting......Pediatrics
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Study Summary Title
Study Summary
Number:
2005-0758
Study Title:A Phase 1/2 Dose-Escalation Study of Clofarabine in Combination with Etoposide and Cyclophosphamide in Pediatric Patients with Refractory or Relapsed Acute Leukemias
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Physician New Patient Referral
Name:Michael E. RyttingPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:PediatricsReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-6620
Contact us about clinical trials
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General Information
Disease Group:Leukemia
Pediatrics
Supported By:N/A
Phase of Study:Phase I/Phase IIReturn
Visit:
Pts in remission who proceed to HSCT will return for f-up quarterly for 2
years; all other pts will return every 6 months for 2 years
Treatment
Agents:
Clofarabine
Cyclophosphamide
Etoposide
G-CSF
Methotrexate
Home Care:G-CSF may be given at home subcutaneously
Treatment Loc:Independent Multicenter Arrangements
Estimated
Length of Stay
in Houston:
3-5 days during treatment, if hospitalization needed
Description/
Intervention:
The goal of the Phase I portion of this clinical research study is to find the
highest tolerable dose of clofarabine (CLOLAR™) that can be given with
etoposide and cyclophosphamide in the treatment of pediatric acute leukemia
patients. The safety and ability of these drugs to control the disease will
also be studied in the Phase II portion of the study.

Phase I of this study has been completed. You will enroll in Phase II.
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Study Objectives / Outcomes
Phase 1 Primary Objective:
To determine the MTD, DLT's and the recommended Phase 2 dose (RP2D) of clofarabine (CLO) when used in combination with etoposide (ETOP) & cyclophosphamide (CPM) and to assess the feasibility and safety of this combination regimen to treat children with refractory or relapsed ALL or AML.

Phase 1 Secondary Objective:
1. To determine the safety and tolerability of CLO when used in combination with ETOP & CPM and determine the duration, seriousness, and relationship of adverse events that occur during the treatment and f-up periods.

2. To determine the overall remission rate (complete remission rate [CR]+ complete remission in the absence of platelet recovery [CRp]) of CLO plus ETOP & CPM in pediatric patients with refractory or relapsed ALL at the established CLO RP2D in combination with ETOP & CPM.

3. To document the rate of partial remission (PR) in the study pop: and

4. To document time-to-event parameters, including duration of remission, event-free survival (EFS), 4-month EFS, and overall survival (OS).


Phase 2 Primary Objective
To estimate the response rate (CR + CRp) at the RP2D in this study pop.

Phase 2 Secondary Objective
1. To determine the duration of remission, EFS and OS in the study pop.

2. To determine the safety and tolerability of CLO when used in combination with ETOP & CPM and the duration seriousness and relationship of adverse events that occur during the treatment and follow-up periods.

3. To document the rate of PR(s) and "any response" (CR + CRp + PR) in the study pop; and

Exploratory Studies


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Study Status Information
Study Activation / Registration Date:05/10/2006
IRB Review and Approval Date:12/07/2005
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Terminated
Projected Accrual:54
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Have a diagnosis of ALL with >25% blasts present in the bone marrow with or without extramedullary disease; or AML according to the WHO classification with >/=5% blasts present in the bone marrow w/ or w/o extramedullary disease. Diagnostic BMA/biopsy should be performed only after all other eligibility criteria have been completed and reviewed, except for the diagnostic LP. BMA/biopsy obtained within 1 week prior to study entry need not be repeated assuming there has been no intervening systemic therapy other than hydroxyurea which is allowed up to 24 hours prior to first dose of study drugs.

2) BM aspirate and/or biopsy obtained within 1 month prior to study entry need not be repeated assuming there has been no intervening systemic therapy other than hydroxyurea which is allowed up to 24 hrs prior to 1st dose of study drugs. [the phase 2 portion of study is open to ALL patients only]

3) Must be >= 1year old and <= 21 years old, and have a body weight of > 10kg

4) Must have Karnofsky Performance Status (KPS) of >=50 for patients > 10years of age and a Lansky Performance Status (LPS) of >=50 for patients <=10 years of age.

5) Patients ( >/=18 years of age) or the parent or legal guardian (for patients <18 years of age) must provide signed, written informed consent according to local IRB and institutional requirements. For patients >/= 7 years of age, but <18 years of age, assent should be obtained according to local IRB and institutional requirements.

6) Patient must be able to comply with study procedures and follow-up examinations.

7) Patient must have adequate liver function defined as Serum bilirubin <= 1.5x ULN for age and AST and ALT <=2.5x ULN

8) Patient must have adequate renal function defined as calculated Creatinine Clearance (Shwartz formula) of >=90mL/min/1.73m^2

9) Patient must have adequate pancreatic function defined as Serum amylase <= 1.5x ULN for age AND Serum lipase <= 1.5x ULN

10) Patient must have adequate cardiac function defined as Echocardiogram with shortening fraction >= 28% (without pharmacologic inotropic support) OR Ejection fraction >= 50%

11) Patient have received no prior hematopoietic stem cell transplant (HSCT).

12) Patient must have no active CNS involvment (ie, should be CNS1 or CNS2) as evidenced by negative cytology on lumbar puncture and absence of clinical syptoms. (Diagnostic lumbar puncture should be performed only after all other eligibility assessments have been completed and reviewed, except for bone marrow aspirate/and or biopsy.

13) Patients with AML must have received no more than 2 prior induction regimens (ie, patients in first or second relapse) AND no more than 1 HSCT

14) Patients with ALL must have received no more than 3 prior induction regimens (ie, patients in second or third relapse or refractory to re-induction in first relapse)

Exclusion Criteria:1) Patients with Burkitt's leukemia (FAB L3-ALL) are excluded. Patients with acute promyelocytic leukemia (FAB M3-AML [APL]) with t(15;17)(q22;q12),(PML/RAR α), or any other variant, are excluded unless the patient has received both all-trans retinoic acid and arsenic trioxide as prior therapy.

2) Patients who received previous treatment with Clofarabine

3) Have an uncontrolled systemic fungal, bacterial, or other infection (eg requiring pressors, supplemental oxygen). In addition, patients must have a temperature < 38.5 degrees C for at least 48 hours prior to study enrollment including negative blood cultures at 48 hours in patients with a history of fever within the preceding 3 days.

4) Patients who are pregnant or lactating. Male and female patients who are fertile must agree to use an effective means of birth control (ie, latex condom, diaphragm, cervical cap, etc) while on study therapy, and for a minimum of 1 month following final study visit.

5) Patients who have psychiatric disorders that would interfere with consent, study participation, or follow-up.

6) Patients who in the opinion of the investigator might not be able to comply with the safety monitoring requirements of the study.

7) Adequate time has not elapsed since pt's last tx. Pts who relapse while receiving standard ALL maintenance chemo do not need a washout period before study entry.

8) Adequate time has not elapsed since pt's last tx. Pts who relapse when they are not receiving standard ALL maintenance tx must have fully recovered from the acute toxic effects of all prior chemo (excluding hematologic toxicity), immunotherapy, or XRT prior to 1st dose of study drug. Also for these pts at least 14 days must have elapsed since the completion of cytotoxic tx. Hydroxyurea may be given to achieve a WBC <50,000/µL prior to starting protocol tx. In these cases there must be at least 48 hrs from the last dose of hydroxyurea and the 1st dose of the study drug

9) Note: patients may receive intrathecal ara-C or methotrexate immediately up to administration of study drug. Biologic (anti-neoplastic agent): Patients must have completed therapy with a biologic agent at least 7 days prior to administration of study drug(s). For patients receiving monoclonal antibody therapy, at least 14 days must have elapsed after completion of therapy.

10) Patients who have any other severe concurrent diseas, or have a history of serious organ dysfunction or diesase involving the heart, kidney, liver or pancreas.

11) Have received a HSCT

12) Have known hepatitis B or C infection or history of cirrhosis.

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Links
Registration Number: NCT00315705
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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