Clinical trial NCT00981799: Trial of Nelarabine, Etoposide and Cyclophosphamide in Relapsed T-cell ALL and T-cell LL
Official title: A Phase I Trial of NECTAR (Nelarabine, Etoposide and Cyclophosphamide in T-ALL Relapse): A Joint Study of TACL and POETIC
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Relapsed T-Cell Acute Lymphoblastic Leukemia
Relapsed T-Cell Lymphoblastic Lymphoma
Keywords: Relapse
T cell
Lymphoblastic
Leukemia
Lymphoma
Nelarabine
TACL
NECTAR
Lead sponsor: Therapeutic Advances in Childhood Leukemia Consortium
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
name: Novartis
First posted: 2009-09-22
Enrollment: 23
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Nelarabine has shown significant activity in patients with T-cell malignancies. This study will determine the safety and maximum tolerated dose of the combination of nelarabine, cyclophosphamide and etoposide in patients with first bone marrow relapse of T-ALL, or first relapse of T-LL.


Eligibility criteria: Inclusion Criteria:

* Patients to be enrolled in the dose-escalation portion of this study must have T-cell ALL or T-cell lymphoblastic lymphoma (LL) in first relapse or must have failed primary induction chemotherapy (ie, never attained a complete remission following an initial course of standard therapy for T-ALL or T-LL). Patients to be enrolled in the cohort expansion portion of this study (ie, those treated at the recommended phase 2 dose) must have T-cell ALL in first relapse or must have failed primary induction chemotherapy (ie, never attained a complete remission following an initial course of standard therapy for T-ALL). T-LL patients are not eligible for the cohort expansion phase.
* 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 Down syndrome are excluded.
* 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.

Primary outcomes:
measure: To Determine the Presence of Dose-limiting Toxicities (DLTs) of Nelarabine, Etoposide and Cyclophosphamide When Given in Combination to Children With T-ALL and Bone Marrow Relapse or T-LL.
timeFrame: 6 months
Secondary outcomes:
measure: To Determine the Complete Remission Rate After 1 and 2 Courses of This Therapy in Children With T-ALL and Bone Marrow Relapse or T-LL.
timeFrame: 1-3 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Childrens Hospital Los Angeles
state: California
city: Orange
country: United States
facility: Children's Hospital Orange County
state: California
city: San Francisco
country: United States
facility: UCSF School of Medicine
state: California
city: Aurora
country: United States
facility: The Children's Hospital, University of Colorado
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Miami
country: United States
facility: University of Miami Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta, Emory University
state: Georgia
city: Chicago
country: United States
facility: Lurie Children's Hospital
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Dana Farber
state: Massachusetts
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Childrens Hospital & Clinics of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospitals and Clinics
state: Missouri
city: New York
country: United States
facility: New York University Medical Center
state: New York
city: New York
country: United States
facility: Children's Hospital New York-Presbyterian
state: New York
city: Charlotte
country: United States
facility: Levine Children's Hospital at Carolinas Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Rainbow Babies
state: Ohio
city: Columbus
country: United States
facility: Nationwide Childrens Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Memphis
country: United States
facility: St. Jude
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Children's Hospital
state: Tennessee
city: Dallas
country: United States
facility: University of Texas at Southwestern
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Westmead
country: Australia
facility: Children's Hospital at Westmead
state: New South Wales
city: Brisbane
country: Australia
facility: Royal Children's Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Royal Children's Hospital, Melbourne
state: Victoria
city: Sydney
country: Australia
facility: Sydney Children's Hospital
city: Vienna
country: Austria
facility: St. Anna Children's Hospital
city: Toronto
country: Canada
facility: Hospital for Sick Kids
state: Ontario
city: Montreal
country: Canada
facility: Sainte Justine University Hospital
state: Quebec
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
city: Lille
country: France
facility: CHU Lille
city: Rome
country: Italy
facility: Bambino Gesù Hospital
city: Rotterdam
country: Netherlands
facility: Erasmus MC - Sophia
Study officials:
affiliation: The Hospital for Sick Children
name: Jim Whitlock, MD
role: STUDY_CHAIR
References: