MT2017-45: CAR-T Cell Therapy for Heme Malignancies

Inclusion Criteria

• •ARM A (Kymriah) and Arm G (Tecartus) :Refractory/relapsed B-cell acute lymphoblastic leukemia expressing CD19
• •Age and Disease Status
• •* Must be age 0-25 years (for Arm A Kymriah) or \>18 years (Arm G Tecartus)
• •* Disease status: Relapsed and refractory pediatric B-cell ALL defined by one of these:
• •* Primary induction failure with no complete remission after ≥2 cycles of induction chemotherapy, or
• •* Patients with persistent minimal residual disease (MRD \>0.01% by flow cytometry or persistent by cytogenetic or molecular assays) after ≥2 cycles of consolidation chemotherapy, or
• •* Patients in 2nd or greater relapse of B-ALL or
• •* Patients with persistent CNS leukemia, or
• •* Down Syndrome or other congenital diseases assuming that they fit the criteria for second or greater relapse or refractory leukemia, or
• •Performance Status
• •\* Arm A: Karnofsky (age ≥16 years) or Lansky (age \< 16 years) performance status ≥ 50% at screening; Arm G: ECOG 0, 1 or 2
• •Organ Function
• •* Renal function defined as:
• •* A serum creatinine of ≤1.5 x ULN OR
• •* eGFR ≥ 50 mL/min/1.73 m2
• •* Liver function defined as:
• •\*\* ALT ≤ 5 times the ULN for age (unless due to disease)
• •\*\* Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
• •* Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 \> 91% on room air
• •* Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
• •* Life expectancy ≥12 weeks
• •* Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
• •* Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
• •Age and Disease Status
• •* Adult patients (age ≥ 18 years)Patients must be ≥18 years of age
• •* One of the following histologies and expression of CD19 by tumor cells:
• •\*\* diffuse large B-cell lymphoma (DLBCL) not otherwise specified, or
• •\*\* primary mediastinal large B-cell lymphoma, or
• •\*\* high grade B-cell lymphoma, or
• •\*\* DLBCL arising from follicular lymphoma
• •* Disease status:
• •\*\* Chemotherapy refractory disease after ≥2 lines of chemotherapy, or
• •\*\* Relapsed with no remission after ≥1 lines of salvage chemotherapy, or
• •\*\* Relapsed following autologous HCT (and failed at least 2 prior lines of therapy including high dose chemotherapy). If salvage therapy is given post autoHCT, the subject must have no response or relapse after the last line of therapy
• •* Measurable disease at time of apheresis: Nodal lesions or extranodal lesion
• •* ECOG performance status 0-2
• •* ALC \>/=100/uL at screening (prior to apheresis)
• •* Renal function defined as:
• •\*\* A serum creatinine of ≤1.5 x ULN OR
• •\*\* eGFR ≥ 50 mL/min/1.73 m2
• •* Liver function defined as:
• •* ALT ≤ 5 times the ULN for age (unless due to disease)
• •* Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
• •* Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 \> 91% on room air
• •* Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
• •* Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as :
• •* Absolute neutrophil count (ANC) \> 1.000/mm3 (only for NHL)
• •* Platelets ≥ 50.000/mm3 (transfusion support can be provided)
• •* Hemoglobin \>8.0 mg/dl (transfusion support can be provided)
• •* Life expectancy ≥12 weeks
• •* Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
• •* Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
• •Age and Disease Status
• •* Adult patients (age ≥ 18 years)
• •* with relapsed or refractory (r/r) large B-cell lymphoma, including
• •* diffuse large B-cell lymphoma (DLBCL) not otherwise specified,
• •* high grade B-cell lymphoma
• •* and DLBCL arising from follicular lymphoma.
• •* Disease status:
• •* after two or more lines of systemic therapy or
• •* relapse after autologous HCT
• •Performance Status
• •* ECOG performance status 0-2
• •* ALC \>/=100/uL at screening (prior to apheresis)
• •Organ Function
• •* Renal function defined as:
• •* A serum creatinine of ≤1.5 x ULN OR
• •* eGFR ≥ 50 mL/min/1.73 m\^2
• •* Liver function defined as:
• •* ALT ≤ 5 times the ULN for age (unless due to disease)
• •* Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
• •* Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 \> 91% on room air
• •* Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
• •* Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as :
• •* Absolute neutrophil count (ANC) \> 1.000/mm3 (only for NHL)
• •* Platelets ≥ 50.000/mm3 (transfusion support can be provided)
• •* Hemoglobin \>8.0 mg/dl (transfusion support can be provided)
• •* Life expectancy ≥12 weeks
• •* Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
• •* Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
• •Age and Disease Status
• •\* with relapsed or refractory (r/r) mantle cell lymphoma, including
• •* prior anthracycline or Bendamustine containing therapy
• •* prior Rituximab or other CD20 directed antibody (or inability to treat with CD20 MoAb)
• •* not a candidate or relapse after autologous HCT
• •* active disease at enrollment
• •Performance Status
• •\*ECOG performance status 0-1
• •Organ Function
• •* Renal function defined as:
• •* A serum creatinine of ≤1.5 x ULN OR
• •* eGFR ≥ 50 mL/min/1.73 m2
• •* Liver function defined as:
• •* ALT ≤ 5 times the ULN for age (unless due to disease)
• •* Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
• •Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 \> 91% on room air
• •Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
• •Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as:
• •Absolute neutrophil count (ANC) \> 1,000/mm\^3 (only for NHL)
• •Platelets ≥ 50,000/mm\^3 (transfusion support can be provided)
• •Hemoglobin \>8.0 mg/dl (transfusion support can be provided)
• •Life expectancy ≥12 weeks
• •Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment. See section 4.5 for definitions of child bearing potential and section 4.6 for definitions of adequate birth control.
• •Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
• •Age and Disease Status
• •* Adult patients (age ≥ 18 years)
• •* with relapsed or refractory disease after two or more lines of systemic therapy, including
• •* diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma),
• •* high-grade B-cell lymphoma,
• •* primary mediastinal large B-cell lymphoma,
• •* follicular lymphoma grade 3B
• •Performance Status
• •\*ECOG performance status 0-2
• •Organ Function
• •* Renal function defined as:
• •* A serum creatinine of ≤1.5 x ULN OR
• •* eGFR ≥ 30 mL/min/1.73 m2
• •* Liver function defined as:
• •* ALT ≤ 5 times the ULN for age (unless due to disease)
• •* Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
• •Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 \> 91% on room air
• •Hemodynamically stable and LVEF ≥ 40% confirmed by echocardiogram or MUGA
• •Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as:
• •* Absolute neutrophil count (ANC) \> 1,000/mm\^3 (only for NHL)
• •* Platelets ≥ 50,000/mm\^3 (transfusion support can be provided)
• •* Hemoglobin \>8.0 mg/dl (transfusion support can be provided)
• •Life expectancy ≥12 weeks
• •Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment. See section 4.5 for definitions of child bearing potential and section 4.6 for definitions of adequate birth control.
• •Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
• •Age and Disease Status
• •* Adult patients (age ≥ 18 years)
• •* Relapsed (progression after prior partial or complete remission) or refractory multiple myeloma
• •* Evidence of active disease (medullary or extramedullary)
• •* Prior therapy (Failure or intolerance to) with an immunomodulatory agent, a proteasome inhibitor, and an antiCD38 monoclonal antibody
• •Performance Status
• •\*ECOG performance status 0-1
• •Organ Function
• •* Renal function defined as:
• •* A serum creatinine of ≤2 x ULN OR
• •* eGFR ≥ 50 mL/min/1.73 m2
• •* Liver function defined as:
• •* ALT ≤ 5 times the ULN for age (unless due to disease)
• •* Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
• •Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 \> 91% on room air
• •Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
• •Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as:
• •* Absolute neutrophil count (ANC) \> 1,000/mm\^3 (only for NHL)
• •* Platelets ≥ 50,000/mm\^3 (transfusion support can be provided)
• •* Hemoglobin \>8.0 mg/dl (transfusion support can be provided)
• •Life expectancy ≥12 weeks
• •Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment. See section 4.5 for definitions of child bearing potential and section 4.6 for definitions of adequate birth control.
• •Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.