A Phase I Trial of NECTAR (Nelarabine, Etoposide and Cyclophosphamide in T-ALL Relapse).

Phase 1

• Conditions: T-cell acute lymphoblastic leukaemia (T-ALL) with bone marrow relapse, relapsed T-cell lymphoblastic lymphoma; MedDRA version: 18.0Level: LLTClassification code 10063621Term: Acute lymphoblastic leukaemia recurrentSystem Organ Class: 100000004864; MedDRA version: 18.0Level: LLTClassification code 10025245Term: Lymphoblastic lymphoma (Precursor T-lymphoblastic lymphoma/leukaemia) recurrentSystem Organ Class: 100000004864

• Registration Number: EUCTR2011-005923-42-GB
• Lead Sponsor: Therapeutic Advances in Childhood Leukemia & Lymphoma

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-11-26
• Last Update Posted: 27 July 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

Age
Patients must be =1 and = 21 years of age at the time of study enrollment.
Diagnosis
Patients to be enrolled in the dose-escalation portion of this study must have T-cell ALL or T-cell lymphoblastic lymphoma 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 (1) greater than 25% blasts in the bone marrow with or without testicular disease, or (2) isolated extramedullary disease such as lymph node or mediastinal involvement. T-ALL patients with extramedullary disease involving only sanctuary sites (ie, testicular relapse) are not eligible.
Patients with T-cell LL or T-ALL followed by isolated extramedullary disease such as lymph node or mediastinal involvement must have disease documented by clinical or radiographic criteria, as well as histologic verification of the malignancy at original diagnosis. Patients with T-cell LL or T-ALL followed by isolated extramedullary disease such as lymph node or mediastinal involvement enrolled in the phase I dose-escalation study are not required to have measurable disease; however, such patients who are enrolled in the phase II cohort expansion at the MTD must have measurable disease so as to be evaluable for response,
Patients may have CNS 1 or CNS 2 disease but not CNS 3.
Performance Level
ECOG 0-2 or Karnofsky = 50% for patients > 16 years of age; Lansky = 50% for patients =16 years of age.
Prior Therapy
Patients who are primary induction failures may have had only 1 previous therapeutic attempt.
Patients who relapse while receiving standard ALL maintenance chemotherapy will not be required to have a waiting period before entry onto this study.
Patients who relapse on therapy other than standard ALL maintenance therapy must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
At least 7 days must have elapsed since the completion of cytotoxic therapy (other than standard ALL maintenance therapy) with the exception of hydroxyurea, which is permitted up to 24 hours prior to the start of protocol therapy.
At least 6 weeks must have elapsed since administration of nitrosureas.
At least 12 weeks must have elapsed since administration of craniospinal, hemipelvic or other radiation therapy to more than 25% of the bone marrow containing spaces.
Patients who have previously been treated with nelarabine are eligible, however if they have previously received a regimen of nelarabine, cyclophosphamide and etoposide, they are not eligible.
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.
Reproductive Function
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 stud

Exclusion Criteria

Diagnosis
Patients are excluded if they have CNS 3 disease as defined in section 10.2.
Patients with isolated extramedullary disease involving only sanctuary sites (ie, testicular relapse) are excluded; patients with extramedullary disease involving nodal or other nonsanctuary sites are eligible.
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)/sinusoidal obstruction syndrome (SOS) or findings consistent with a diagnosis of VOD/SOS, 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.
Prior Therapy
Patients are excluded if they have had
•Previous hematopoietic stem cell transplantation;
•A prior seizure disorder requiring anti-convulsant therapy. For the purposes of this study, this includes any patient that has received any therapy to prevent/treat seizures in the 2 years prior to study enrollment.
Infection Criteria
Patients are excluded if they have:
•Positive blood culture within 48 hours of study enrollment;
•Fever above 38.2 within 48 hours of study enrollment with clinical signs of infection.
Fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability.
•Active fungal, viral, bacterial, or protozoal infection requiring IV treatment. Chronic prophylaxis therapy to prevent infections is allowed.
Plan to administer non-protocol chemotherapy, radiation therapy, immunotherapy, or any other investigational agents 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified