| Eligibility |
Inclusion Criteria:
1. Signed informed consent form
2. Documentation of CD19 expression on malignant cells
a. ALL/CLL: At time of most recent relapse b. NHL: Within 6 months of
physician-investigator confirmation of eligibility as long as there has been no
intervening CD19 directed therapy since expression confirmed. Results outside of this
window may be used, if there is no accessible tumor site and the subject did not
receive intervening CD19 directed therapy since CD19 expression was confirmed.
3. Patients with relapsed disease after prior autologous or allogeneic SCT must meet the
following criteria:
a. Have no active GVHD and require no immunosuppression b. Are more than 6 months from
transplant at the time of physician-investigator confirmation of eligibility
4. Adequate organ function defined as:
1. Creatinine = 1.6 mg/dl
2. ALT/AST = 3x upper limit of normal range
3. Direct bilirubin =2.0 mg/dl, unless the subject has Gilbert's syndrome (=3.0
mg/dl)
4. Must have a minimum level of pulmonary reserve defined as = Grade 1 dyspnea,
pulse oxygen > 92% on room air, and DLCO = 40% (corrected for anemia)
5. Left Ventricle Ejection Fraction (LVEF) = 40% confirmed by ECHO/MUGA
5. Evidence of active disease. This could include circulating disease in the blood,
disease in the bone marrow by standard morphology (or by MRD testing for ALL
patients), or measurable disease per Lugano Criteria (NHL patients).
6. Male or female age = 18 years.
7. ECOG Performance Status that is either 0 or 1.
8. Subjects of reproductive potential must agree to use acceptable birth control methods.
9. Disease-specific criteria:
a. Cohort A i. Patients with relapsed or refractory B cell ALL which meets one of the
following criteria:
1. Relapsed or refractory B cell ALL with 2nd or greater relapse or refractory to 1st
salvage as defined by:
a. Recurrent disease in the blood or bone marrow identified morphologically, by
immunohistochemistry or by Flow cytometry.
b. Patients with extramedullary relapse only (no bone marrow involvement) will be
eligible if disease response can be assessed radiographically, OR
2. Refractory B cell ALL as defined by:
a. Failure to achieve remission (<5% bone marrow blasts) after 2 cycles of induction
chemotherapy b. Patients that achieve morphologic remission but remain MRD+ after =2
cycles of induction chemotherapy, OR
3. Ph+ relapsed or refractory B cell ALL that is intolerant to or have failed a tyrosine
kinase inhibitor therapy containing regimen.
ii. Patients with prior or current history of CNS3 disease* will be eligible only if CNS
disease is responsive to therapy (at infusion, must meet criteria in Section 5.2) 1. *CNS
disease definitions70:
a. CNS1 - no blasts seen on cytocentrifuge (CNS negative); b. CNS2 - total nucleated cell
count <5x106/L, but blasts seen on cytocentrifuge; c. CNS3 - total nucleated cell count
5x106/L with blasts on cytocentrifuge and/or signs of CNS leukemia (i.e. cranial nerve
palsy).
b. Cohort B (CLL) i. Patients must have relapsed/refractory disease after at least 2 prior
lines of appropriate therapy, AND ii. Patients must have previously received, or be
intolerant to an approved BTK inhibitor and venetoclax; unless a BTK inhibitor or
venetoclax is contraindicated.
c. Cohort B (NHL)- With one of the following diagnoses: i. Diffuse Large B-cell Lymphoma
1. Patients with any of the following histologies:
1. Diffuse large B-cell lymphoma (DLBCL), NOS
i. Germinal center B-cell type ii. Activated B-cell type b. Primary cutaneous DLBCL,
leg type c. Primary mediastinal (thymic) large B-cell lymphoma d. ALK+ large B-cell
lymphoma e. High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements
(i.e. "Double or Triple Hit") f. High-grade B-cell lymphoma, NOS
2. Patients must have relapsed after, or be ineligible for, prior CAR T cell therapy, and
meet one of the following criteria:
1. Relapsed/refractory disease after at least 2 prior lines of appropriate therapy
and are ineligible for autologous stem cell transplant or commercial CAR T cell
therapy.
2. Relapse/refractory disease after autologous SCT.
3. Relapsed/refractory disease after allogeneic SCT. ii. Large cell transformation
of CLL (Richter's transformation)
1. Patients must be primary refractory or received at least 1 prior line of treatment.
iii. Follicular lymphoma 1. Patients who have received at least 2 prior lines of
appropriate therapy (not including single agent monoclonal antibody therapy), AND 2.
Progressed within 2 years after second or higher line of therapy. iv. Mantle cell lymphoma
1. Patients must have either failed or be ineligible for standard of care Tecartus™
(brexucabtagene autoleucel) or other investigational CAR T cell product; and
2. Patients must also meet one of the following criteria:
1. Relapsed/refractory disease after at least 2 prior lines of appropriate therapy,
including a BTK inhibitor. Single-agent monoclonal antibody therapy does not
count towards prior lines of therapy.
2. Relapsed/refractory disease after prior autologous SCT.
3. Relapsed/refractory disease after prior allogeneic SCT..
Exclusion Criteria:
1. Active hepatitis B, active hepatitis C, or other active, uncontrolled infection.
2. Class III/IV cardiovascular disability according to the New York Heart Association
Classification.
3. Clinically apparent arrhythmia or arrhythmias who are not stable on medical management
within two weeks of physician-investigator confirmation of eligibility.
4. Active acute or chronic GVHD requiring systemic therapy.
5. Dependence on systemic steroids or immunosuppressant medications. For additional
details regarding use of steroid and immunosuppressant medications.
6. Receipt of immune checkpoint inhibitors within 4 months prior to
physician-investigator confirmation of eligibility.
7. CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions.
8. Pregnant or nursing (lactating) women.
9. Patients with a known history or prior diagnosis of optic neuritis or other
immunologic or inflammatory disease affecting the central nervous system, and
unrelated to their cancer or previous cancer treatment.
10. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to
= 10mg of prednisone. Patients with autoimmune neurologic diseases (such as MS) will
be excluded.
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