Recruitment

Recruitment Status
Recruiting
Estimated Enrollment
52

Inclusion Criteria

Pulmonary function (measured prior to treatment):
Oxygen saturation ≥ 90% on room air
AST ≤ 5 x the institutional ULN Elevation secondary to leukemic involvement is not an exclusion criterion. Leukemic involvement will be determined by the presence of progressive relapse defined by escalating bone marrow or peripheral blood leukemia blasts within the previous month and the absence of initiation of know hepatotoxic medication (e.g. azoles).
...
Pulmonary function (measured prior to treatment):
Oxygen saturation ≥ 90% on room air
AST ≤ 5 x the institutional ULN Elevation secondary to leukemic involvement is not an exclusion criterion. Leukemic involvement will be determined by the presence of progressive relapse defined by escalating bone marrow or peripheral blood leukemia blasts within the previous month and the absence of initiation of know hepatotoxic medication (e.g. azoles).
Renal function (measured prior to conditioning chemotherapy)
History of CD19+ relapse/refractory (R/R) B cell malignancies occurring after allogeneic/autologous HSCT or solid organ transplant (SOT. (cohort 1)
History of relapsed or refractory CD19+ malignancies (e.g. Non Hodgkin Lymphoma) or considered high risk for relapse and and require autologous or allogeneic hematopoietic stem cell transplant (HSCT). Evidence of disease not required. (cohort 2 and 3)
Adequate cardiac function (e.g. LVEF ≥ 40%) as assessed by ECHO or MUGA or other similar cardia imaging performed within 1 month of treatment.
Relapse on this protocol is detection of CD19+ malignancies in bone marrow morphology ≥ 5% any extramedullary lesion (radiographic), or detection of any disease level by cytogenetics, molecular, and/or flow cytometry.
Creatinine ≤ 2.0mg/dL for patients over 18 years of ≤ 2.5 x institutional ULN for age.
No age restriction for patients
Total bilirubin ≤ 2.5 x the institutional ULN
KPS or Lansky score > or = to 50
Hepatic function (measured prior to conditioning chemotherapy):

Exclusion Criteria

New York Heart Association (NYHA) stage III or IV congestive heart failure
Subjects receiving hydroxyurea or oral maintenance chemotherapy may be enrolled provided there has been no increase in dose for at least 2 weeks prior to starting apheresis or treatment
Uncontrolled, symptomatic, intercurrent illness including but not limited to infection, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the treating investigator would pose an unacceptable risk to the subject.
...
New York Heart Association (NYHA) stage III or IV congestive heart failure
Subjects receiving hydroxyurea or oral maintenance chemotherapy may be enrolled provided there has been no increase in dose for at least 2 weeks prior to starting apheresis or treatment
Uncontrolled, symptomatic, intercurrent illness including but not limited to infection, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the treating investigator would pose an unacceptable risk to the subject.
Patients with any concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation.
Adult patients (≥18 years old) with the following cardiac conditions will be excluded:
Subjects receiving steroid therapy at physiological replacement doses only are allowed provided there has been no increase in dose for at least 2 weeks prior to subject starting apheresis or treatment.
History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration.
Rapidly progressive disease that in the estimation of the treating physician would compromise ability to complete study therapy.
There is no time restriction in regard to prior intrathecal chemotherapy provided tere is complete recovery from any acute toxic effects of such.
Subjects must have recovered from the acute side effects of their prior therapy, such that eligibility criteria are met. Cytopenias deemed to be disease-related and not therapy-related are exempt from this exclusion.
Prior irreversible neurologic toxicity to previous immunotherapy
Recent prior therapy: Systematic chemotherapy less than 2 weeks prior to infusion.
Myocardial infarction ≤ 6months prior to enrollment
History of severe non-ischemic cardiomyopathy with EF ≤20%
Preceding and/or ongoing organ dysfunction or other co-morbidity including but not limited to uncontrolled infection that would impair the patient's ability to endure known side effects of cytokine release syndrome or neurological toxicity
Females who are pregnant.
Patients will be excluded if they have isolated extra-medullary relapse of ALL.
Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF) or symptomatic CNS leukemia (i.e. cranial nerve palsies or other significant neurologic dysfunction) within 28 days of treatment. Prophylactic intrathecal medication is not a reason for exclusion.
Patients with active HIV, hepatitis B or hepatitis C infection.
Patients with active (grade 2-4) acute graft versus host disease (GVHD), chronic GVHD or an overt autoimmune disease (e.g. hemolytic anemia) requiring glucocorticosteroid treatment (>0.5 mg/kg/day prednisone or its equivalent) as treatment

Summary

Conditions
  • Acute Lymphocytic Leukemia
  • Lymphoma
Type
Interventional
Phase
Phase 1
Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Intervention Model Description: This is a phase I trial designed to identify tolerable and clinically active doses of allogeneic Epstein - Barr virus specific cytotoxic T lymphocytes (EBV-CTLs) genetically modified to target the B-cell antigen CD19 when administered to patients with CD19+Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Younger than 125 years
Gender
Both males and females

Inclusion Criteria

Pulmonary function (measured prior to treatment):
Oxygen saturation ≥ 90% on room air
AST ≤ 5 x the institutional ULN Elevation secondary to leukemic involvement is not an exclusion criterion. Leukemic involvement will be determined by the presence of progressive relapse defined by escalating bone marrow or peripheral blood leukemia blasts within the previous month and the absence of initiation of know hepatotoxic medication (e.g. azoles).
...
Pulmonary function (measured prior to treatment):
Oxygen saturation ≥ 90% on room air
AST ≤ 5 x the institutional ULN Elevation secondary to leukemic involvement is not an exclusion criterion. Leukemic involvement will be determined by the presence of progressive relapse defined by escalating bone marrow or peripheral blood leukemia blasts within the previous month and the absence of initiation of know hepatotoxic medication (e.g. azoles).
Renal function (measured prior to conditioning chemotherapy)
History of CD19+ relapse/refractory (R/R) B cell malignancies occurring after allogeneic/autologous HSCT or solid organ transplant (SOT. (cohort 1)
History of relapsed or refractory CD19+ malignancies (e.g. Non Hodgkin Lymphoma) or considered high risk for relapse and and require autologous or allogeneic hematopoietic stem cell transplant (HSCT). Evidence of disease not required. (cohort 2 and 3)
Adequate cardiac function (e.g. LVEF ≥ 40%) as assessed by ECHO or MUGA or other similar cardia imaging performed within 1 month of treatment.
Relapse on this protocol is detection of CD19+ malignancies in bone marrow morphology ≥ 5% any extramedullary lesion (radiographic), or detection of any disease level by cytogenetics, molecular, and/or flow cytometry.
Creatinine ≤ 2.0mg/dL for patients over 18 years of ≤ 2.5 x institutional ULN for age.
No age restriction for patients
Total bilirubin ≤ 2.5 x the institutional ULN
KPS or Lansky score > or = to 50
Hepatic function (measured prior to conditioning chemotherapy):

Exclusion Criteria

New York Heart Association (NYHA) stage III or IV congestive heart failure
Subjects receiving hydroxyurea or oral maintenance chemotherapy may be enrolled provided there has been no increase in dose for at least 2 weeks prior to starting apheresis or treatment
Uncontrolled, symptomatic, intercurrent illness including but not limited to infection, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the treating investigator would pose an unacceptable risk to the subject.
...
New York Heart Association (NYHA) stage III or IV congestive heart failure
Subjects receiving hydroxyurea or oral maintenance chemotherapy may be enrolled provided there has been no increase in dose for at least 2 weeks prior to starting apheresis or treatment
Uncontrolled, symptomatic, intercurrent illness including but not limited to infection, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the treating investigator would pose an unacceptable risk to the subject.
Patients with any concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation.
Adult patients (≥18 years old) with the following cardiac conditions will be excluded:
Subjects receiving steroid therapy at physiological replacement doses only are allowed provided there has been no increase in dose for at least 2 weeks prior to subject starting apheresis or treatment.
History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration.
Rapidly progressive disease that in the estimation of the treating physician would compromise ability to complete study therapy.
There is no time restriction in regard to prior intrathecal chemotherapy provided tere is complete recovery from any acute toxic effects of such.
Subjects must have recovered from the acute side effects of their prior therapy, such that eligibility criteria are met. Cytopenias deemed to be disease-related and not therapy-related are exempt from this exclusion.
Prior irreversible neurologic toxicity to previous immunotherapy
Recent prior therapy: Systematic chemotherapy less than 2 weeks prior to infusion.
Myocardial infarction ≤ 6months prior to enrollment
History of severe non-ischemic cardiomyopathy with EF ≤20%
Preceding and/or ongoing organ dysfunction or other co-morbidity including but not limited to uncontrolled infection that would impair the patient's ability to endure known side effects of cytokine release syndrome or neurological toxicity
Females who are pregnant.
Patients will be excluded if they have isolated extra-medullary relapse of ALL.
Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF) or symptomatic CNS leukemia (i.e. cranial nerve palsies or other significant neurologic dysfunction) within 28 days of treatment. Prophylactic intrathecal medication is not a reason for exclusion.
Patients with active HIV, hepatitis B or hepatitis C infection.
Patients with active (grade 2-4) acute graft versus host disease (GVHD), chronic GVHD or an overt autoimmune disease (e.g. hemolytic anemia) requiring glucocorticosteroid treatment (>0.5 mg/kg/day prednisone or its equivalent) as treatment

Tracking Information

NCT #
NCT01430390
Collaborators
Not Provided
Investigators
  • Principal Investigator: Kevin Curran, MD Memorial Sloan Kettering Cancer Center
  • Kevin Curran, MD Memorial Sloan Kettering Cancer Center
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