| Eligibility |
Inclusion Criteria- Lymphodepletion
The patient must fulfill all of the following inclusion criteria to participate in this
compassionate use protocol:
- Written informed consent for use of compassionate use therapy signed by patient or
legal guardian of a pediatric patient.
- Age 3 to 17 years of age for pediatric patient (weight must be = 10 kg), = 18 to 70
years of age for an adult patient at the time of consent.
- Relapsed or refractory precursor B cell ALL:
- Second or greater bone marrow relapse OR
- Any bone marrow relapse >100 days after allogeneic stem cell transplant OR
- Primary refractory ALL defined as no complete response after 2 cycles of a
standard of care chemotherapy regimen OR
- For an adult patient: first bone marrow relapse with duration of first CR <1 year
OR CR1 duration =1 year and refractory to =1 cycle of therapy for treatment of
relapse
- A patient with isolated non-CNS extramedullary disease will be eligible as long
as the time-of-remission criteria above for bone marrow relapses or primary
refractory ALL are met and the biopsy for extramedullary disease confirms CD19
expression
- For a pediatric patient: first bone marrow or isolated non-CNS extramedullary
relapse refractory to 1 cycle of standard therapy for relapsed ALL
- While active CNS3 leukemia will be excluded, any patient with concurrent CNS3
disease and bone marrow relapse who has responded to CNS-directed therapy prior
to enrollment will be allowed to participate. Intrathecal chemotherapy will be
allowed to continue between lymphodepleting chemotherapy and cell infusion.
- Patients with CNS2 disease and concurrent bone marrow relapse will be eligible.
Intrathecal chemotherapy will be allowed to continue between lymphodepleting
chemotherapy and cell infusion
- Patients with Ph+ ALL will be eligible if they have failed = 2 ABL tyrosine kinase
inhibitors. Patients with the T315I ABL kinase point mutation will be eligible if they
have failed ponatinib-containing therapy, regardless of the number of prior ABL
tyrosine kinase inhibitors.
- CD19 positivity of lymphoblasts confirmed by flow cytometry or IHC per institutional
standards.
- Karnofsky score > 60% if =16 years old or Lansky performance score of greater than 60%
if <16 years old (See Appendix A: Performance Status (Lansky and Karnofsky)).
- Life expectancy = 12 weeks.
- Patients who have received prior therapy with murine antibodies must have
documentation of absence of human anti-mouse antibodies (HAMA) prior to
lymphodepletion on this study.
- Demonstrate adequate renal and hepatic function as defined in the table below; all
screening labs to be obtained within 72 hrs prior to lymphodepletion.
- Serum Creatinine: = 1.5 x ULN
- Bilirubin: = 1.5 x upper limit of normal (ULN), unless attributed to Gilbert's
Syndrome
- Aspartate Aminotransferase (AST): = 3.0 × ULN
- Alanine aminotransferase (ALT): = 3.0 × ULN
- For pediatric patients, adequate renal function is defined below:
Age Maximum Serum Creatinine (mg/dL) Male Female 3 to <6 years =0.8 =0.8 6 to <10 years =1
=1 10 to <13 years =1.2 =1.2 13 to <16 years =1.5 =1.4 16 to <18 years =1.7 =1.4
- Females of childbearing potential must have a negative serum pregnancy test within 72
hours prior to lymphodepletion. NOTE: Females are considered of child bearing
potential unless they are premenarchal, surgically sterile (have undergone a
hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are
naturally postmenopausal for at least 12 consecutive months
- Females and males of childbearing potential must be willing to abstain from
heterosexual activity or to use 2 forms of effective methods of contraception from the
time of informed consent until 3 months after treatment discontinuation. The two
contraception methods can be comprised of two barrier methods, or a barrier method
plus a hormonal method. Female patients will inform their male partners that they must
use the methods of birth control required by the protocol.
- Male patients with female partners must have had a prior vasectomy or agree to use an
adequate method of contraception (i.e., double barrier method: condom plus spermicidal
agent) starting with the first dose of study therapy through 3 months after the last
dose of study therapy.
- As determined by the enrolling physician or protocol designee, ability of the patient
to understand and comply with compassionate use protocol procedures.
- Patients currently receiving "maintenance" doses of chemotherapy are eligible and the
need for intrathecal prophylaxis prior to lymphodepletion is left to the discretion of
the investigator. Maintenance chemotherapy is defined as methotrexate =30 mg/m2/week,
mercaptopurine =100 mg/m2/day and vincristine = 2 mg/28 days. For patients who receive
chemotherapy, including intrathecal chemotherapy, that does not fit this definition of
maintenance chemotherapy, a two week washout between the last dose of standard of care
chemotherapy and the beginning of lymphodepletion will be required.
- Patients must have leftover autologous transduced activated T-cells from the LCCC
1541-ATL clinical protocol that meet the Certificate of Analysis (CofA) acceptance
criteria.
Exclusion Criteria- Lymphodepletion
Patients meeting any of the following criteria CANNOT participate in this compassionate use
protocol:
- Patients with relapsed fulminant CD19+ ALL that is rapidly progressing.
- Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use if the
milk is collected while the mother is being treated on study).
- Has a known additional malignancy that is active and/or progressive requiring
treatment; exceptions include basal cell or squamous cell skin cancer, in situ
cervical or bladder cancer, or other cancer for which the subject has been
disease-free for at least five years.
- Patients must not have tumor in a location where enlargement could cause airway
obstruction.
- Patients may not have an oxygen requirement as defined by pulse oximetry of < 90% on
room air.
- Treatment with any investigational drug within 14 days (i.e., two weeks) prior to
lymphodepletion or has received any tumor vaccines within the previous five weeks
prior to lymphodepletion.
- Patients with the following known systemic viral infections will be excluded: active
HIV, HTLV, HBV, HCV.
- Patients who are on treatment for other active uncontrolled infections (not referenced
above) with resolution of signs/symptoms are not excluded. Non-influenza, non-RSV,
isolated upper respiratory infections are not excluded. Other active uncontrolled
infections will be excluded.
- Use of systemic corticosteroids at doses =10mg/day prednisone or its equivalent; those
receiving <10mg/day may be enrolled at discretion of investigator. (Note:
Corticosteroid use with doses at the discretion of the treating physician are allowed
after procurement up to the beginning of lymphodepletion.). Physiologic replacement
with hydrocortisone is allowed at 6-12 mg/m2/day, or equivalent.
Inclusion Criteria- iC9-CAR19 Cell Infusion
Subjects must fulfill all of the following inclusion criteria to participate in this
compassionate use protocol:
- Females and males of childbearing potential must be willing to abstain from
heterosexual activity or to use 2 forms of effective methods of contraception from the
time of informed consent until 3 months after treatment discontinuation. The two
contraception methods can be comprised of two barrier methods, or a barrier method
plus a hormonal method. Female patients will inform their male partners that they must
use the methods of birth control required by the protocol.
- Male patients with female partners must have had a prior vasectomy or agree to use an
adequate method of contraception (i.e., double barrier method: condom plus spermicidal
agent) starting with the first dose of study therapy through 3 months after the last
dose of study therapy.
- As determined by the enrolling physician or protocol designee, ability of the patient
to understand and comply with compassionate use protocol procedures.
Exclusion Criteria- iC9-CAR19 Cell Infusion
Subjects meeting any of the following criteria CANNOT be enrolled in this study:
- Corticosteroid use is contraindicated following iC9-CAR19 infusion unless medically
necessary e.g., to treat CRS).
- Severe systemic uncontrolled disease or toxicities that develop after lymphodepletion
may prompt exclusion from cell infusion at the discretion of the investigator.
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