Trial of Nelarabine, Etoposide and Cyclophosphamide in Relapsed T-cell ALL and T-cell LL
NCT ID: NCT00981799
Last Updated: 2020-10-01
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE1/PHASE2
23 participants
INTERVENTIONAL
2010-06-30
2016-07-18
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Nelarabine Dose Level 1
The study will begin at Dose Level 1 at 480 mg/m2 Nelarabine (75% of single agent maximum tolerated dose) and 330 mg/m2 Cyclophospamide and will escalate to the next Dose Level if the maximum tolerated dose (MTD) is not exceeded. The first 3 patients will be enrolled into Dose Level 1. If 0/3 experiences dose limiting toxicity (DLT) at a given dose level, then the dose is escalated to the next higher level and 3 more patients are enrolled. If 1/3 experiences DLT at current dose, the up to 3 more patients are accrued at the same dose level. If 2 or more DLTs are observed in a 3-patient or 6-patient cohort at a given dose level, then the MTD has been exceeded, dose escalation will be stopped, and up to 3 additional patients will be enrolled at the next lower dose level (unless 6 patients have already been treated at that prior dose). If the MTD is exceeded at Dose Level 0, the study will be closed.
Nelarabine
Dose will be assigned at study entry. Nelarabine will be given IV over 60 minutes (given at hours 0 to 1) on days 1 through 5.
Etoposide
100 mg/m2/day IV over 2 hours (given at hours 1 to 3) on days 1 through 5
Cyclophosphamide
Dose will be assigned at study entry, IV as a 30-60 minute infusion (given at hours 3 to 4) on days 1 through 5.
Methotrexate
Give between day 29 and 36 or when ANC\>750 and PLTS\>75,000 - whichever comes first (but not prior to day 22) at the dose defined by age below, ideally in conjunction with BM evaluation.
Given intrathecally at the dose defined by age below. 8 mg for patients age greater than or equal to 1, but \<2 years of age 10 mg for patients age greater than or equal to 2, but \<3 years of age 12 mg for patients greater than or equal to 3, but \< 9 years of age 15 mg for patients greater than or equal to \>9 years of age
Filgrastim
5 micrograms/kg/day IV or SC will begin on Day 6 and end when the ANC is \> 1000/mm3 for two consecutive days.
Nelarabine Dose Level 2
Patients in this arm will be administered Nelarabine at 650 mg/m2 (100% of single agent MTD) and 330 mg/m2 Cyclophosphamide.
Nelarabine
Dose will be assigned at study entry. Nelarabine will be given IV over 60 minutes (given at hours 0 to 1) on days 1 through 5.
Etoposide
100 mg/m2/day IV over 2 hours (given at hours 1 to 3) on days 1 through 5
Cyclophosphamide
Dose will be assigned at study entry, IV as a 30-60 minute infusion (given at hours 3 to 4) on days 1 through 5.
Methotrexate
Give between day 29 and 36 or when ANC\>750 and PLTS\>75,000 - whichever comes first (but not prior to day 22) at the dose defined by age below, ideally in conjunction with BM evaluation.
Given intrathecally at the dose defined by age below. 8 mg for patients age greater than or equal to 1, but \<2 years of age 10 mg for patients age greater than or equal to 2, but \<3 years of age 12 mg for patients greater than or equal to 3, but \< 9 years of age 15 mg for patients greater than or equal to \>9 years of age
Filgrastim
5 micrograms/kg/day IV or SC will begin on Day 6 and end when the ANC is \> 1000/mm3 for two consecutive days.
Nelarabine Dose Level 3
Patients in this arm will be administered Nelarabine at 650 mg/m2 (100% of single agent MTD) and 400 mg/m2 Cyclophosphamide
Nelarabine
Dose will be assigned at study entry. Nelarabine will be given IV over 60 minutes (given at hours 0 to 1) on days 1 through 5.
Etoposide
100 mg/m2/day IV over 2 hours (given at hours 1 to 3) on days 1 through 5
Cyclophosphamide
Dose will be assigned at study entry, IV as a 30-60 minute infusion (given at hours 3 to 4) on days 1 through 5.
Methotrexate
Give between day 29 and 36 or when ANC\>750 and PLTS\>75,000 - whichever comes first (but not prior to day 22) at the dose defined by age below, ideally in conjunction with BM evaluation.
Given intrathecally at the dose defined by age below. 8 mg for patients age greater than or equal to 1, but \<2 years of age 10 mg for patients age greater than or equal to 2, but \<3 years of age 12 mg for patients greater than or equal to 3, but \< 9 years of age 15 mg for patients greater than or equal to \>9 years of age
Filgrastim
5 micrograms/kg/day IV or SC will begin on Day 6 and end when the ANC is \> 1000/mm3 for two consecutive days.
Nelarabine Dose Level 0
Patients in this arm will be administered Nelarabine 325 mg/m2 (50% of single agent MTD) and 330 mg/2 Cyclophosphamide. Patients will only enter this arm if the MTD at Dose Level 1 has been exceeded. If the MTD is exceeded at Dose Level 0, the study will be closed.
Nelarabine
Dose will be assigned at study entry. Nelarabine will be given IV over 60 minutes (given at hours 0 to 1) on days 1 through 5.
Etoposide
100 mg/m2/day IV over 2 hours (given at hours 1 to 3) on days 1 through 5
Cyclophosphamide
Dose will be assigned at study entry, IV as a 30-60 minute infusion (given at hours 3 to 4) on days 1 through 5.
Methotrexate
Give between day 29 and 36 or when ANC\>750 and PLTS\>75,000 - whichever comes first (but not prior to day 22) at the dose defined by age below, ideally in conjunction with BM evaluation.
Given intrathecally at the dose defined by age below. 8 mg for patients age greater than or equal to 1, but \<2 years of age 10 mg for patients age greater than or equal to 2, but \<3 years of age 12 mg for patients greater than or equal to 3, but \< 9 years of age 15 mg for patients greater than or equal to \>9 years of age
Filgrastim
5 micrograms/kg/day IV or SC will begin on Day 6 and end when the ANC is \> 1000/mm3 for two consecutive days.
Interventions
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Nelarabine
Dose will be assigned at study entry. Nelarabine will be given IV over 60 minutes (given at hours 0 to 1) on days 1 through 5.
Etoposide
100 mg/m2/day IV over 2 hours (given at hours 1 to 3) on days 1 through 5
Cyclophosphamide
Dose will be assigned at study entry, IV as a 30-60 minute infusion (given at hours 3 to 4) on days 1 through 5.
Methotrexate
Give between day 29 and 36 or when ANC\>750 and PLTS\>75,000 - whichever comes first (but not prior to day 22) at the dose defined by age below, ideally in conjunction with BM evaluation.
Given intrathecally at the dose defined by age below. 8 mg for patients age greater than or equal to 1, but \<2 years of age 10 mg for patients age greater than or equal to 2, but \<3 years of age 12 mg for patients greater than or equal to 3, but \< 9 years of age 15 mg for patients greater than or equal to \>9 years of age
Filgrastim
5 micrograms/kg/day IV or SC will begin on Day 6 and end when the ANC is \> 1000/mm3 for two consecutive days.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Patients with T-cell ALL must have greater than 25% blasts in the bone marrow with or without extramedullary disease.
* Patients with T-cell LL must have recurrent disease, documented by clinical or radiographic criteria, as well as histologic verification of the malignancy at original diagnosis. Patients with T-cell LL enrolled in the phase I dose-escalation study are not required to have measurable disease; however, patients enrolled in the phase II cohort expansion at the MTD must have measurable disease.
* Patients may have CNS 1 or CNS 2 disease but not CNS 3.
* ECOG 0-2 or Karnofsky ≥ 50% for patients \> 16 years of age; Lansky ≥ 50% for patients ≤16 years of age.
* Patients may be enrolled on study regardless of the timing of prior Intrathecal therapy; however, they MAY NOT BEGIN TREATMENT ON THIS PROTOCOL UNTIL A MINIMUM OF 7 DAYS HAS ELAPSED SINCE PRIOR INTRATHECAL THERAPY.
* At least 6 weeks must have elapsed since administration of nitrosureas.
* At least 12 weeks must have elapsed since administration of craniospinal or hemipelvic radiation.
* Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed within 2 weeks 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 and for a minimum of 6 months after study treatment.
* Adequate renal function defined as serum creatinine ≤ 1.5x upper limit of normal (ULN) for age. If the serum creatinine is above these values, the calculated creatinine clearance or radioisotope GFR must be ≥ 70 mL/min/1.73m2.
* Total bilirubin ≤ 1.5x ULN for age. If the total bilirubin is elevated, patient will still be eligible if the conjugated (direct) serum bilirubin ≤ ULN for age.
* ALT ≤ 5x ULN of normal for age.
* Adequate cardiac function defined as shortening fraction of ≥ 27% by echocardiogram or ejection fraction ≥ 45% by gated radionuclide study.
* No evidence of dyspnea at rest
* No exercise intolerance
* A pulse oximetry ≥ 94% at sea level (≥ 90% at altitude ≥ 5000 feet) if there is clinical indication for determination.
* Patients and/or their parents or legal guardians must be capable of understanding the investigational nature, potential risks and benefits of the study. All patients and/or their parents or legal guardians must sign a written informed consent.
Exclusion Criteria
* Patients with pre-existing Grade 2 (or greater) peripheral motor or sensory neurotoxicity per the CTCAE 3.0 as determined by the treating physician or a neurologist.
* Patients with a history of prior veno-occlusive disease (VOD) or findings consistent with a diagnosis of VOD, defined as: conjugated serum bilirubin \>1.4 mg/dL AND unexplained weight gain greater than 10% of baseline weight or ascites AND hepatomegaly or right upper quadrant pain without another explanation, OR reversal of portal vein flow on ultrasound, OR pathological confirmation of VOD on liver biopsy.
* Previous hematopoetic stem cell transplantation.
* Patients with a prior seizure disorder requiring anti-convulsant therapy are not eligible to receive nelarabine. For the purposes of this study, this includes any patient that has received anticonvulsant therapy to prevent/treat seizures in the prior two years.
* Positive blood culture within 48 hours of study enrollment.
* Fever above 38.2 within 48 hours of study enrollment with clinical signs of infection.
* Plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period.
* Any 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.
1 Year
21 Years
ALL
No
Sponsors
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GlaxoSmithKline
INDUSTRY
Novartis
INDUSTRY
Therapeutic Advances in Childhood Leukemia Consortium
OTHER
Responsible Party
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Principal Investigators
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Jim Whitlock, MD
Role: STUDY_CHAIR
The Hospital for Sick Children
Locations
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Childrens Hospital Los Angeles
Los Angeles, California, United States
Children's Hospital Orange County
Orange, California, United States
UCSF School of Medicine
San Francisco, California, United States
The Children's Hospital, University of Colorado
Aurora, Colorado, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
University of Miami Cancer Center
Miami, Florida, United States
Children's Healthcare of Atlanta, Emory University
Atlanta, Georgia, United States
Lurie Children's Hospital
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
Childrens Hospital & Clinics of Minnesota
Minneapolis, Minnesota, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States
New York University Medical Center
New York, New York, United States
Children's Hospital New York-Presbyterian
New York, New York, United States
Levine Children's Hospital at Carolinas Medical Center
Charlotte, North Carolina, United States
Rainbow Babies
Cleveland, Ohio, United States
Nationwide Childrens Hospital
Columbus, Ohio, United States
Oregon Health and Science University
Portland, Oregon, United States
St. Jude
Memphis, Tennessee, United States
Vanderbilt Children's Hospital
Nashville, Tennessee, United States
University of Texas at Southwestern
Dallas, Texas, United States
Cook Children's Hospital
Fort Worth, Texas, United States
Primary Children's
Salt Lake City, Utah, United States
Seattle Children's Hospital
Seattle, Washington, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Children's Hospital at Westmead
Westmead, New South Wales, Australia
Royal Children's Hospital
Brisbane, Queensland, Australia
Royal Children's Hospital, Melbourne
Melbourne, Victoria, Australia
Sydney Children's Hospital
Sydney, , Australia
St. Anna Children's Hospital
Vienna, , Austria
Hospital for Sick Kids
Toronto, Ontario, Canada
Sainte Justine University Hospital
Montreal, Quebec, Canada
British Columbia Children's Hospital
Vancouver, , Canada
CHU Lille
Lille, , France
Bambino Gesù Hospital
Rome, , Italy
Erasmus MC - Sophia
Rotterdam, , Netherlands
Countries
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Related Links
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For more information about this and other clinical trials, please visit the TACL website
Other Identifiers
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T2008-002
Identifier Type: -
Identifier Source: org_study_id
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