Nelarabine, etoposide, and cyclophosphamide in relapsed pediatric T-acute lymphoblastic leukemia and T-lymphoblastic lymphoma (study T2008-002 NECTAR)
James A. Whitlock
Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
Search for more papers by this authorJemily Malvar
Division of Hematology, Oncology and Blood and Marrow Transplantation, Department of Pediatrics, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA
The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, USA
Search for more papers by this authorLuciano Dalla-Pozza
The Children's Hospital at Westmead, Westmead, New South Wales, Australia
Search for more papers by this authorJohn M. Goldberg
University of Miami Miller School of Medicine, Miami, Florida, USA
Search for more papers by this authorLewis B. Silverman
Dana-Farber Cancer Institute/Boston Children's Hospital, Boston, Massachusetts, USA
Search for more papers by this authorDavid S. Ziegler
Kids Cancer Centre, Sydney Children's Hospital, Randwick, New South Wales, Australia
School of Women's and Children's Health, University of New South Wales, Sydney, Australia
Search for more papers by this authorAndishe Attarbaschi
Department of Pediatric Hematology and Oncology, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorPatrick A. Brown
Johns Hopkins University/Sidney Kimmel Cancer Center, Baltimore, Maryland, USA
Search for more papers by this authorRebecca A. Gardner
Seattle Children's Hospital, Seattle, Washington, USA
Search for more papers by this authorPaul S. Gaynon
Children's Center for Cancer and Blood Disease, Children's Hospital of Los Angeles, Los Angeles, California, USA
Search for more papers by this authorRaymond Hutchinson
Department of Pediatrics, Hematology and Oncology, C.S. Mott Children's Hospital, University of Michigan, Ann Arbor, Michigan, USA
Search for more papers by this authorVan T. Huynh
Children's Hospital Orange County, Orange, California, USA
Search for more papers by this authorSima Jeha
Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
Search for more papers by this authorLeigh Marcus
Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland, USA
Search for more papers by this authorYoav Messinger
Children's Hospital and Clinics of Minnesota, Minneapolis, Minnesota, USA
Search for more papers by this authorKirk R. Schultz
BC Children's Hospital and Research Institute, Vancouver, British Columbia, Canada
Search for more papers by this authorJeannette Cassar
Children's Oncology Group, Monrovia, California, USA
Search for more papers by this authorFranco Locatelli
Ospedale Bambino Gesù, University of Pavia, Rome, Italy
Search for more papers by this authorC. Michel Zwaan
Pediatric Oncology/Hematology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, Netherlands
Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands
Search for more papers by this authorBrent L. Wood
Seattle Cancer Care Alliance, Seattle, Washington, USA
Search for more papers by this authorRichard Sposto
The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, USA
Division of Hematology, Oncology and Blood and Marrow Transplantation, Department of Pediatrics and Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA
Search for more papers by this authorCorresponding Author
Lia Gore
Department of Pediatrics, University of Colorado School of Medicine/Children's Hospital Colorado, Aurora, Colorado, USA
Correspondence
Lia Gore, Section of Pediatric Hematology/Oncology/Bone Marrow Transplant-Cellular Therapeutics, Children's Hospital Colorado and the University of Colorado School of Medicine, 13123 East 16th Ave, Box B115, Aurora, CO 80045, USA.
Email: [email protected]
Search for more papers by this authorJames A. Whitlock
Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
Search for more papers by this authorJemily Malvar
Division of Hematology, Oncology and Blood and Marrow Transplantation, Department of Pediatrics, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA
The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, USA
Search for more papers by this authorLuciano Dalla-Pozza
The Children's Hospital at Westmead, Westmead, New South Wales, Australia
Search for more papers by this authorJohn M. Goldberg
University of Miami Miller School of Medicine, Miami, Florida, USA
Search for more papers by this authorLewis B. Silverman
Dana-Farber Cancer Institute/Boston Children's Hospital, Boston, Massachusetts, USA
Search for more papers by this authorDavid S. Ziegler
Kids Cancer Centre, Sydney Children's Hospital, Randwick, New South Wales, Australia
School of Women's and Children's Health, University of New South Wales, Sydney, Australia
Search for more papers by this authorAndishe Attarbaschi
Department of Pediatric Hematology and Oncology, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorPatrick A. Brown
Johns Hopkins University/Sidney Kimmel Cancer Center, Baltimore, Maryland, USA
Search for more papers by this authorRebecca A. Gardner
Seattle Children's Hospital, Seattle, Washington, USA
Search for more papers by this authorPaul S. Gaynon
Children's Center for Cancer and Blood Disease, Children's Hospital of Los Angeles, Los Angeles, California, USA
Search for more papers by this authorRaymond Hutchinson
Department of Pediatrics, Hematology and Oncology, C.S. Mott Children's Hospital, University of Michigan, Ann Arbor, Michigan, USA
Search for more papers by this authorVan T. Huynh
Children's Hospital Orange County, Orange, California, USA
Search for more papers by this authorSima Jeha
Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
Search for more papers by this authorLeigh Marcus
Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland, USA
Search for more papers by this authorYoav Messinger
Children's Hospital and Clinics of Minnesota, Minneapolis, Minnesota, USA
Search for more papers by this authorKirk R. Schultz
BC Children's Hospital and Research Institute, Vancouver, British Columbia, Canada
Search for more papers by this authorJeannette Cassar
Children's Oncology Group, Monrovia, California, USA
Search for more papers by this authorFranco Locatelli
Ospedale Bambino Gesù, University of Pavia, Rome, Italy
Search for more papers by this authorC. Michel Zwaan
Pediatric Oncology/Hematology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, Netherlands
Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands
Search for more papers by this authorBrent L. Wood
Seattle Cancer Care Alliance, Seattle, Washington, USA
Search for more papers by this authorRichard Sposto
The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, USA
Division of Hematology, Oncology and Blood and Marrow Transplantation, Department of Pediatrics and Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA
Search for more papers by this authorCorresponding Author
Lia Gore
Department of Pediatrics, University of Colorado School of Medicine/Children's Hospital Colorado, Aurora, Colorado, USA
Correspondence
Lia Gore, Section of Pediatric Hematology/Oncology/Bone Marrow Transplant-Cellular Therapeutics, Children's Hospital Colorado and the University of Colorado School of Medicine, 13123 East 16th Ave, Box B115, Aurora, CO 80045, USA.
Email: [email protected]
Search for more papers by this authorPreliminary data from this trial were previously presented in abstract form at the 2014 Annual Meeting of the American Society of Hematology (https://doi.org/10.1182/blood.V124.21.795.795).
Abstract
Children with relapse of T-cell acute lymphoblastic leukemia (T-ALL) or lymphoblastic lymphoma (T-LBL) have a dismal prognosis, largely due to difficulty attaining second remission. We hypothesized that adding etoposide and cyclophosphamide to the nucleoside analog nelarabine could improve response rates over single-agent nelarabine for relapsed T-ALL and T-LBL. This phase I dose-escalation trial's primary objective was to evaluate the dose and safety of nelarabine given in combination with etoposide at 100 mg/m2/day and cyclophosphamide at 330–400 mg/m2/day, each for 5 consecutive days in children with either T-ALL (13 patients) or T-LBL (10 patients). Twenty-three patients were treated at three dose levels; 21 were evaluable for dose-limiting toxicities (DLT) and response. The recommended phase II doses (RP2D) for this regimen, when given daily ×5 every 3 weeks, were nelarabine 650 mg/m2/day, etoposide 100 mg/m2/day, and cyclophosphamide 400 mg/m2/day. DLTs included peripheral motor and sensory neuropathies. An expansion cohort to evaluate responses at the RP2D was terminated early due to slow accrual. The overall best response rate was 38% (8/21), with 33% (4/12) responses in the T-ALL cohort and 44% (4/9) responses in the T-LBL cohort. These response rates are comparable to those seen with single-agent nelarabine in this setting. These data suggest that the addition of cyclophosphamide and etoposide to nelarabine does not increase the incidence of neurologic toxicities or the response rate beyond that obtained with single-agent nelarabine in children with first relapse of T-ALL and T-LBL.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interest.
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