EZN-3042 Administered With Re-induction Chemotherapy in Children With Relapsed Acute Lymphoblastic Leukemia (ALL)
Overview[ - collapse ][ - ]
| Purpose | An experimental drug called EZN-3042 targets survivin, a protein expressed in leukemia cells at relapse that promotes the leukemia cells to grow. The main goal of this phase I study is to find out the dose of EZN-3042 that can be safely given without serious side effects both alone and in combination with standard chemotherapy drugs during re-induction. |
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| Condition | Lymphoblastic Leukemia, Acute Lymphoblastic Leukemia, Acute, Childhood Leukemia, Lymphoblastic, Acute, T Cell Leukemia, Lymphoblastic, Acute |
| Intervention | Drug: EZN-3042 Drug: Cytarabine Drug: Doxorubicin Drug: Prednisone Drug: Vincristine Drug: Pegaspargase Drug: Methotrexate |
| Phase | Phase 1 |
| Sponsor | Therapeutic Advances in Childhood Leukemia Consortium |
| Responsible Party | Therapeutic Advances in Childhood Leukemia Consortium |
| ClinicalTrials.gov Identifier | NCT01186328 |
| First Received | August 19, 2010 |
| Last Updated | March 7, 2012 |
| Last verified | March 2012 |
Tracking Information[ + expand ][ + ]
| First Received Date | August 19, 2010 |
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| Last Updated Date | March 7, 2012 |
| Start Date | August 2010 |
| Estimated Primary Completion Date | June 2012 |
| Current Primary Outcome Measures |
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| Current Secondary Outcome Measures |
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Descriptive Information[ + expand ][ + ]
| Brief Title | EZN-3042 Administered With Re-induction Chemotherapy in Children With Relapsed Acute Lymphoblastic Leukemia (ALL) |
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| Official Title | T2009-007: A Phase I Study Evaluating the Safety, Tolerability and Biological Activity of EZN-3042, a Survivin mRNA Antagonist, Administered With Re-induction Chemotherapy in Children With Relapsed Acute Lymphoblastic Leukemia (ALL) [IND 108753] |
| Brief Summary | An experimental drug called EZN-3042 targets survivin, a protein expressed in leukemia cells at relapse that promotes the leukemia cells to grow. The main goal of this phase I study is to find out the dose of EZN-3042 that can be safely given without serious side effects both alone and in combination with standard chemotherapy drugs during re-induction. |
| Detailed Description | This is a phase I multi-site study of the new investigational agent EZN-3042, which is highly effective at blocking survivin and inhibiting survivin protein expression. Survivin plays pivotal roles in tumor formation by inhibiting cell death and regulating cell cycle progression. The primary objective is to study EZN-3042 in children with relapsed acute lymphoblastic leukemia (ALL). Patients will receive 2 doses of EZN-3042 prior to initiating systemic therapy with vincristine, doxorubicin, prednisone and PEG-asparaginase. In addition, blood and bone marrow specimens will be drawn to measure minimal residual disease (MRD), pharmacokinetic levels of EZN-3042 and survivan expression. The study will follow a standard 3+3 dose escalation design. We hypothesize that EZN-3042 will be safe, tolerable and biologically active, when given both alone and in combination with standard re-induction chemotherapy. |
| Study Type | Interventional |
| Study Phase | Phase 1 |
| Study Design | Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment |
| Condition |
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| Intervention | Drug: EZN-3042 Dose will be assigned at study entry. To be given as a 2 hour intravenous infusion on days -5, -2, 8, 15, 22 and 29. Drug: Cytarabine Given intrathecally on day -6 at the dose defined by age. Age 1-1.99 get 30 mg, age 2-2.99 get 50 mg, and age greater than or equal to 3 get 70 mg. Other Names:
60 mg/m2/day given intravenous infusion (IV) over 15 minutes on day 1. Other Names:
40 mg/m2/day divided twice or three times a day given orally on days 1 through 29. Other Names:
.5 mg/m2/day (maximum dose 2 mg) given intravenous push over 1 minute or infusion via mini-bag as per institutional policy on days 1, 8, 15 and 22. Other Names:
2500 IU/m2 intramuscular injection on days 2, 9, 16, 23. Other Names:
Given intrathecally to patients with central nervous system 1 and central nervous system 2 disease at the dose defined by age below on days 15 and 36. Age 1-1.99 get 8 mg, age 2-2.99 get 10 mg, age 3-8.99 get 12 mg and greater than or equal to age 9 get 15 mg. Other Names:
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| Study Arm (s) | Not Provided |
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Terminated |
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| Estimated Enrollment | 6 |
| Estimated Completion Date | June 2012 |
| Estimated Primary Completion Date | February 2012 |
| Eligibility Criteria | Inclusion Criteria: - Patients must be ≥1 and ≤ 21 years of age when originally diagnosed with acute lymphoblastic leukemia (ALL). - Patients must have a diagnosis of second or greater relapse B-precursor acute lymphoblastic leukemia (ALL) with ≥25% blasts in the bone marrow (M3), with or without extramedullary disease. - Patients may have central nervous system 1, 2 or 3 disease. - Karnofsky ≥ 50 for patients > 10 years of age and Lansky ≥ 50 for patients ≤ 10 years of age. - Patients who relapse while receiving standard ALL maintenance chemotherapy will not be required to have a waiting period before entry onto this study. - Patients who relapse when they are not receiving standard ALL maintenance therapy must have fully recovered from grade 3 or 4 toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. - Cytotoxic Therapy: It must be at least 14 days since the completion of cytotoxic therapy (excluding hydroxyurea) at the time of study enrollment. - Hematopoietic Stem Cell Transplant (HSCT): Patients who have experienced their relapse after a HSCT are eligible, provided they have no evidence of active Graft-versus-Host Disease (GVHD) and are at least 120 days post-transplant at the time of enrollment. - Prior anthracycline exposure: Patients must have ≤ 400 mg/m2 lifetime exposure of anthracycline chemotherapy. - Biologic (anti-neoplastic) therapy: It must be at least 7 days since the completion of therapy with a biologic agent at the time of study enrollment. For agents that have known adverse events occurring 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. - Patients must have a calculated creatinine clearance or radioisotope GRF ≥ 70mL/min/1.73m2 OR a normal serum creatinine based on the institutional normal values according to age. - Patient's ALT must be < 5 x institutional upper limit of norm (ULN), unless the elevation is suspected to be disease-related. - Patient's total bilirubin must be ≤ 1.5 x ULN. - Patient's serum albumin must be ≥ 2 g/dL. - Patient must have prothrombin time (PT), partial thromboplastin time (PTT) and international normalized ratio (INR) ≤ 1.5 times the ULN. - Patient must have a shortening fraction ≥ 27% by echocardiogram or an ejection fraction ≥ 45% by gated nucleotide study. - Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed prior to enrollment. - Female patients with infants must agree not to breastfeed their infants while on this study. - Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study. Exclusion Criteria: - Patients with Down syndrome are excluded. - Patients with B-cell ALL (L3 morphology or evidence of myc translocation by molecular or cytogenetic technique) are not eligible - Patients with documented active and uncontrolled infection at the time of study entry are not eligible. - Patient will be excluded if they are currently receiving other investigational drugs. - Patients will be excluded if they are taking strong CYP3A4 inducers or inhibitors. - Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period. - Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results. |
| Gender | Both |
| Ages | 1 Year |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | United States, Australia, Brazil, Canada |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT01186328 |
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| Other Study ID Numbers | T2009-007 |
| Has Data Monitoring Committee | Yes |
| Information Provided By | Therapeutic Advances in Childhood Leukemia Consortium |
| Study Sponsor | Therapeutic Advances in Childhood Leukemia Consortium |
| Collaborators | Enzon Pharmaceuticals, Inc. |
| Investigators | Study Chair: Elizabeth Raetz, MD New York University School of MedicineStudy Chair: William Carroll, MD New York University School of Medicine |
| Verification Date | March 2012 |
Locations[ + expand ][ + ]
| Phoenix Children's Hospital | Phoenix, Arizona, United States |
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| City of Hope | Duarte, California, United States, 91010 |
| Miller Children's Hospital | Long Beach, California, United States |
| Childrens Hospital Los Angeles | Los Angeles, California, United States, 90027 |
| Oakland Children's Hospital | Oakland, California, United States |
| Stanford University Medical Center | Palo Alto, California, United States, 94304-1812 |
| UCSF School of Medicine | San Francisco, California, United States, 94143-0106 |
| Children's Healthcare of Atlanta, Emory University | Atlanta, Georgia, United States |
| Children's Memorial | Chicago, Illinois, United States |
| Johns Hopkins University | Baltimore, Maryland, United States |
| Dana Farber | Boston, Massachusetts, United States |
| C.S. Mott Children's Hospital | Ann Arbor, Michigan, United States, 48109-0914 |
| Childrens Hospital & Clinics of Minnesota | Minneapolis, Minnesota, United States, 55404-4597 |
| University of Minnesota Children's Hospital | Minneapolis, Minnesota, United States |
| Children's Hospital New York-Presbyterian | New York, New York, United States, 10032 |
| New York University Medical Center | New York, New York, United States, 10016 |
| Nationwide Childrens Hospital | Columbus, Ohio, United States |
| Oregon Health and Science University | Portland, Oregon, United States |
| St. Jude | Memphis, Tennessee, United States, 38105-3678 |
| Vanderbilt Children's Hospital | Nashville, Tennessee, United States |
| Seattle Children's Hospital | Seattle, Washington, United States, 98105 |
| Sydney Children's Hospital | Sydney, Australia |
| Children's Hospital at Westmead | Westmead, NSW, Australia |
| Instituto De Oncologia Pediatrica | Sao Paulo, Brazil |
| Hospital for Sick Kids | Toronto, Ontario, Canada |
| Alberta Children's Hospital | Calgary, Canada |
| British Columbia Children's Hospital | Vancouver, Canada |