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Trial of Nelarabine, Etoposide and Cyclophosphamide in Relapsed T-cell ALL and T-cell LL

Information source: Therapeutic Advances in Childhood Leukemia Consortium
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Relapsed T-Cell Acute Lymphoblastic Leukemia; Relapsed T-Cell Lymphoblastic Lymphoma

Intervention: Nelarabine (Drug); Etoposide (Drug); Cyclophosphamide (Drug); Methotrexate (Drug); Filgrastim (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Therapeutic Advances in Childhood Leukemia Consortium

Official(s) and/or principal investigator(s):
Jim Whitlock, MD, Study Chair, Affiliation: The Hospital for Sick Children

Overall contact:
Jeannette van der Giessen, BA, Phone: 323-361-8725, Email: jvandergiessen@chla.usc.edu

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.

Clinical Details

Official title: A Phase I Trial of NECTAR (Nelarabine, Etoposide and Cyclophosphamide in T-ALL Relapse): A Joint Study of TACL and POETIC

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

Primary outcome: To determine the maximum tolerated doses and 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.

Secondary outcome:

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.

To determine the percent of children with T-ALL and 1st BM relapse that have a complete response after therapy on this study and proceed to stem cell transplantation in complete response within 20 weeks of beginning this regimen.

To determine minimal residual disease (MRD) levels at the end of each course of treatment.

To evaluate the vitamin B12 pathway and metabolites and the potential association of neurotoxicity following nelarabine therapy with alterations in this pathway.

To determine, in a preliminary manner, whether patients with relapsed T-ALL/LL have a distinct signaling signature that distinguishes malignant cells from normal thymocytes.

To evaluate, in a preliminary manner, whether phospho-flow cytometry can be used to predict clinical response to Nelarabine.

Eligibility

Minimum age: 1 Year. Maximum age: 21 Years. Gender(s): Both.

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.

Locations and Contacts

Jeannette van der Giessen, BA, Phone: 323-361-8725, Email: jvandergiessen@chla.usc.edu

Sydney Children's Hospital, Sydney, Australia; Recruiting

Children's Hospital at Westmead, Westmead, NSW, Australia; Recruiting

St. Anna Children's Hospital, Vienna, Austria; Recruiting
Andische Attarbaschi, MD, PhD

British Columbia Children's Hospital, Vancouver, Canada; Recruiting

CHU Lille, Lille, France; Recruiting
Brigitte Nelken, MD, Phd

Bambino Gesù Hospital, Rome, Italy; Recruiting
Franco Locatelli, MD, PhD

Erasmus MC - Sophia, Rotterdam, Netherlands; Recruiting
Michel Zwaan, MD, PhD

Childrens Hospital Los Angeles, Los Angeles, California 90027, United States; Recruiting
Paul S. Gaynon, MD, Principal Investigator

Children's Hospital Orange County, Orange, California, United States; Recruiting

UCSF School of Medicine, San Francisco, California 94143-0106, United States; Recruiting
Steven DuBois, MD, Principal Investigator

The Children's Hospital, University of Colorado, Aurora, Colorado 80045, United States; Recruiting
Lia Gore, MD, Principal Investigator

Children's National Medical Center, Washington, District of Columbia, United States; Recruiting

University of Miami Cancer Center, Miami, Florida 33136, United States; Recruiting
John Goldberg, MD, Principal Investigator

Children's Healthcare of Atlanta, Emory University, Atlanta, Georgia, United States; Recruiting

Lurie Children's Hospital, Chicago, Illinois, United States; Recruiting
Nobuko Hijiya, MD, Principal Investigator

Johns Hopkins University, Baltimore, Maryland, United States; Recruiting

Dana Farber, Boston, Massachusetts, United States; Recruiting

C.S. Mott Children's Hospital, Ann Arbor, Michigan 48109-0914, United States; Recruiting
Raymond Hutchinson, MD, Principal Investigator

Childrens Hospital & Clinics of Minnesota, Minneapolis, Minnesota 55404-4597, United States; Recruiting
Bruce Bostrom, MD, Principal Investigator
Yoav Messinger, MD, Principal Investigator

Children's Mercy Hospitals and Clinics, Kansas City, Missouri 64108, United States; Recruiting
Kathleen Neville, MD, Principal Investigator

Children's Hospital New York-Presbyterian, New York, New York 10032, United States; Recruiting
Julia Glade-Bender, MD, Principal Investigator

New York University Medical Center, New York, New York 10016, United States; Recruiting
Elizabeth Raetz, MD, Principal Investigator

Levine Children's Hospital at Carolinas Medical Center, Charlotte, North Carolina 28203, United States; Recruiting
Javier Oesterheld, MD
Javier Oesterheld, MD, Principal Investigator

Rainbow Babies, Cleveland, Ohio, United States; Recruiting
Joe Matloub, MD

Nationwide Childrens Hospital, Columbus, Ohio, United States; Recruiting

Hospital for Sick Kids, Toronto, Ontario, Canada; Recruiting

Oregon Health and Science University, Portland, Oregon, United States; Recruiting

Sainte Justine University Hospital, Montreal, Quebec, Canada; Recruiting
Henrique Bittencourt, MD

Royal Children's Hospital, Brisbane, Queensland, Australia; Recruiting

St. Jude, Memphis, Tennessee 38105-3678, United States; Recruiting
Deepa Bhojwani, MD

Vanderbilt Children's Hospital, Nashville, Tennessee, United States; Recruiting

University of Texas at Southwestern, Dallas, Texas, United States; Recruiting

Cook Children's Hospital, Fort Worth, Texas, United States; Recruiting
Ken Heym, MD

Primary Children's, Salt Lake City, Utah, United States; Recruiting
Elizabeth Raetz, MD

Royal Children's Hospital, Melbourne, Melbourne, Victoria, Australia; Recruiting

Seattle Children's Hospital, Seattle, Washington 98105, United States; Recruiting
Blythe Thompson, MD, Principal Investigator

Medical College of Wisconsin, Milwaukee, Wisconsin, United States; Recruiting
Mike Burke, MD

Additional Information

For more information about this and other clinical trials, please visit the TACL website

Starting date: June 2010
Last updated: December 3, 2014

Page last updated: August 23, 2015

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