Relapsed T-Cell Acute Lymphoblastic Leukemia Clinical Trial
Official title:
A Phase I Trial of NECTAR (Nelarabine, Etoposide and Cyclophosphamide in T-ALL Relapse): A Joint Study of TACL and POETIC
| Verified date | September 2020 |
| Source | Therapeutic Advances in Childhood Leukemia Consortium |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Terminated |
| Enrollment | 23 |
| Est. completion date | July 18, 2016 |
| Est. primary completion date | November 2015 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 1 Year to 21 Years |
| Eligibility |
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. |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Royal Children's Hospital | Brisbane | Queensland |
| Australia | Royal Children's Hospital, Melbourne | Melbourne | Victoria |
| Australia | Sydney Children's Hospital | Sydney | |
| Australia | Children's Hospital at Westmead | Westmead | New South Wales |
| Austria | St. Anna Children's Hospital | Vienna | |
| Canada | Sainte Justine University Hospital | Montreal | Quebec |
| Canada | Hospital for Sick Kids | Toronto | Ontario |
| Canada | British Columbia Children's Hospital | Vancouver | |
| France | CHU Lille | Lille | |
| Italy | Bambino Gesù Hospital | Rome | |
| Netherlands | Erasmus MC - Sophia | Rotterdam | |
| United States | C.S. Mott Children's Hospital | Ann Arbor | Michigan |
| United States | Children's Healthcare of Atlanta, Emory University | Atlanta | Georgia |
| United States | The Children's Hospital, University of Colorado | Aurora | Colorado |
| United States | Johns Hopkins University | Baltimore | Maryland |
| United States | Dana Farber | Boston | Massachusetts |
| United States | Levine Children's Hospital at Carolinas Medical Center | Charlotte | North Carolina |
| United States | Lurie Children's Hospital | Chicago | Illinois |
| United States | Rainbow Babies | Cleveland | Ohio |
| United States | Nationwide Childrens Hospital | Columbus | Ohio |
| United States | University of Texas at Southwestern | Dallas | Texas |
| United States | Cook Children's Hospital | Fort Worth | Texas |
| United States | Children's Mercy Hospitals and Clinics | Kansas City | Missouri |
| United States | Childrens Hospital Los Angeles | Los Angeles | California |
| United States | St. Jude | Memphis | Tennessee |
| United States | University of Miami Cancer Center | Miami | Florida |
| United States | Medical College of Wisconsin | Milwaukee | Wisconsin |
| United States | Childrens Hospital & Clinics of Minnesota | Minneapolis | Minnesota |
| United States | Vanderbilt Children's Hospital | Nashville | Tennessee |
| United States | Children's Hospital New York-Presbyterian | New York | New York |
| United States | New York University Medical Center | New York | New York |
| United States | Children's Hospital Orange County | Orange | California |
| United States | Oregon Health and Science University | Portland | Oregon |
| United States | Primary Children's | Salt Lake City | Utah |
| United States | UCSF School of Medicine | San Francisco | California |
| United States | Seattle Children's Hospital | Seattle | Washington |
| United States | Children's National Medical Center | Washington | District of Columbia |
| Lead Sponsor | Collaborator |
|---|---|
| Therapeutic Advances in Childhood Leukemia Consortium | GlaxoSmithKline, Novartis |
United States, Australia, Austria, Canada, France, Italy, Netherlands,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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. | Patients will be evaluated based on Dose Level and total courses taken at each dose level and for presence of dose limiting toxicities. Not all patients enrolled at each dose level has been assessed to be evaluable for DLTs. Only those that have met criteria for being evaluable for DLT will be counted in the Overall Number of Participants Analyzed. | 6 months | |
| Secondary | 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. | Patients will be evaluated at each dose level and for assessment of response to treatment. Not all patients enrolled at each dose level has been assessed to be evaluable for response. Only those that have met criteria for being evaluable for response will be counted in the Overall Number of Participants Analyzed. | 1-3 months |