A Safety and Tolerability Study of Clofarabine, Etoposide, Cyclophosphamide, PEG-asparaginase, and Vincristine in Pediatric Acute Lymphoblastic Leukemia (ALL)

NCT00991133 | Completed Phase 1 DMC

• 1 other identifier: CLO08808
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 6

Brief Summary

This is an open-label study of Clofarabine, Etoposide, Cyclophosphamide, PEG-asparaginase, and Vincristine to assess this 5-drug treatment's safety and tolerability in pediatric patients with first relapse Acute Lymphoblastic Leukemia (ALL).

Conditions

Lymphoblastic Leukemia, Acute, Childhood

Outcome Measures

Primary Outcomes (1)

• 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)

  1 cycle

Secondary Outcomes (2)

• Overall toxicity profile documented by incidence of AEs, SAEs, and/or DLTs

  1 cycle

• Efficacy as documented by complete remission (CR), time and duration of remission, event-free survival (EFS), 4-month EFS, disease-free survival (DFS), and overall survival

  2 cycles

Study Arms (1)

Clofarabine

EXPERIMENTAL

Patients received a maximum of 2 cycles of the intravenous (IV) 5-drug regimen (clofarabine, etoposide,cyclophosphamide, PEG-asparaginase, and vincristine) plus intrathecal methotrexate, and then entered follow-up. Patients who achieved complete remission (CR) or complete remission with incomplete platelet recovery (CRp) after 1 cycle of study drugs were eligible to receive a second cycle of study drugs upon recovery of peripheral blood counts, and patients who did not have leukemic progression were eligible to receive a second treatment cycle at the investigator's discretion.

Drug: Clofarabine incorporated into a 5-drug regimen

Interventions

Clofarabine incorporated into a 5-drug regimen DRUG

Clofarabine (IV) 40mg/m2 into an intensive chemotherapy regimen of etoposide, cyclophosphamide, PEG-asparaginas, and vincristine

Also known as: Clolar, VP-16, Cytoxan, PEGaspar-aginase, Oncovin

Clofarabine

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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 therapy.
• 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 radiotherapy.
• 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 required.
• 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 follow-up.
• 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.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (6)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

The Children's Hospital

Aurora, Colorado, 80045, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Children's Memorial Hospital

Chicago, Illinois, 60614, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Clofarabine; Etoposide; Cyclophosphamide; Vincristine

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2009
• First Posted: October 7, 2009
• Study Start: October 1, 2009
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: April 30, 2015

Record last verified: 2015-04

Locations

US (6)