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A Phase 1, Open-Label, Multi-Center Safety and Tolerability Pilot Combination Study of Clofarabine, Etoposide, Cyclophosphamide, PEG-asparaginase, and Vincristine in Pediatric Patients With Acute Lymphoblastic Leukemia (ALL) in First Relapse

Phase 1
1 Year
30 Years
Not Enrolling
Lymphoblastic Leukemia, Acute, Childhood

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Trial Information

A Phase 1, Open-Label, Multi-Center Safety and Tolerability Pilot Combination Study of Clofarabine, Etoposide, Cyclophosphamide, PEG-asparaginase, and Vincristine in Pediatric Patients With Acute Lymphoblastic Leukemia (ALL) in First Relapse

The trial is a Phase 1, open-label study to assess the safety and tolerability of
incorporating clofarabine into an intensive chemotherapy regimen of etoposide,
cyclophosphamide, PEG-asparaginase, and vincristine. Patients enrolled in this study will
receive a maximum of 2 cycles of the 5-drug regimen, then will be treated according to
investigator discretion. After the study treatment period, all patients will be followed for
a minimum of 4 months beyond the final study visit. This study will include a maximum of 12
evaluable patients.

Inclusion Criteria:

- Be in first relapse with >25% blasts in the bone marrow with a duration of first
remission of ≥6 months and no longer in the intensive phase(s) of initial ALL therapy
(e.g., patients who are in the maintenance or continuation phases of therapy [or
beyond] and who have completed the induction or intensification phases).

- Have received no more than 2 prior induction regimens prior to the date of first
relapse. Patients who are in first relapse but have failed a re-induction attempt
(i.e., 1 cycle of re-induction therapy) are not eligible for inclusion in this study.

- Be ≥1 and ≤30 years old and have a body weight of >10 kg at study entry. (Note: no
more than 3 patients aged >21 ≤30 are to be enrolled.)

- Be able to receive all study drugs with no known contra-indications.

- Be able to provide adequate venous access.

- Have a Karnofsky Performance Status (KPS) of ≥50 for patients >10 years of age or a
Lansky Performance Status (LPS) of ≥50 for patients ≤10 years of age.

- Patients (≥18 years of age) or the parent or legal guardian(s) (for patients <18
years of age) must provide signed, written informed consent according to local
institutional review board (IRB) and institutional requirements. For patients <18
years of age, signed assent should be obtained according to local IRB and
institutional requirements.

- Be able to comply with study procedures and follow-up examinations.

- Have adequate liver, renal, pancreatic, and cardiac function considered acceptable by
laboratory values and cardiac assessments

- Have no active central nervous system (CNS) leukemia, as evidenced by negative
cytology on lumbar puncture and absence of clinical central neurologic symptoms.
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. Patients with CNS1 or CNS2 leukemia may be enrolled in the study.

- Have recovered to baseline from all toxicities from prior chemotherapy regimens prior
to enrollment in the study.

Exclusion Criteria:

- Have received previous treatment with clofarabine.

- Have a history of clinical allergy (Grade 3 or 4) to PEG-asparaginase.

- Have a history of severe pancreatitis (Grade 3 or 4) attributed to asparaginase

- Have Burkitt's leukemia.

- Have overt testicular relapse.

- Adequate time has not elapsed since patient's last therapy. Patients who relapse
while receiving standard ALL maintenance chemotherapy will not be required to have a
washout period before entry onto this study. Note that patients may receive
intrathecal (IT) ara-C, methotrexate, or hydrocortisone immediately prior to the
administration of study drugs. Patients may also receive hydroxyurea up to 24 hours
prior to the start of study therapy. Patients who relapse when they are not receiving
standard ALL maintenance therapy must have fully recovered from the acute toxic
effects of all prior therapy (excluding hematologic toxicity), immunotherapy or

- Have an uncontrolled systemic fungal, bacterial, viral, or other infection. For
patients with a history of fever within the preceding 3 days at the time of
enrollment, documentation of negative blood cultures for at least 48 hours is

- Are pregnant or lactating.

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

- Have psychiatric disorders that would interfere with consent, study participation, or

- Have any other severe concurrent disease, or have a history of serious organ
dysfunction or disease involving the heart, kidney, liver, or pancreas.

- Have received any stem cell transplantation or high-dose chemotherapy with stem cell
rescue regimen.

- Have a history of cirrhosis or known human immunodeficiency virus (HIV)/acquired
immunodeficiency syndrome (AIDS).

- Have a history of at least 1 positive test for hepatitis B or hepatitis C infection.

- Have Down syndrome.

- Are currently participating in another concurrent investigational treatment protocol.

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The incidence of DLTs (Dose Limiting Toxicities) experienced with 1 cycle of this 5-drug regimen in this patient population (in all patients who receive any doses of study drugs)

Outcome Time Frame:

1 cycle

Safety Issue:


Principal Investigator

Medical Monitor

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

October 2009

Completion Date:

April 2011

Related Keywords:

  • Lymphoblastic Leukemia, Acute, Childhood
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma



Children's Hospital Los AngelesLos Angeles, California  90027-0700
Dana Farber Cancer InstituteBoston, Massachusetts  02115
Children's Memorial HospitalChicago, Illinois  60614
Children's Healthcare of AtlantaAtlanta, Georgia  30342
Seattle Children's HospitalSeattle, Washington  98105
The Children'S HospitalDenver, Colorado  80218