Description:
This is a single center, open-label, phase 1 study to determine the safety and feasibility of
infusing CART22-65s with or without huCART19 after administration of lymphodepleting
chemotherapy in adult patients with relapsed or refractory B-ALL.
Title
- Brief Title: CART22 Alone or in Combination With huCART19 for ALL
- Official Title: Phase 1 Study of Autologous Anti-CD22 Chimeric Antigen Receptor Redirected T Cells (CART22-65s) Alone and When Co-administered With Humanized Anti-CD19 Chimeric Antigen Receptor Redirected T Cells (huCART19) In Patients With Chemotherapy Resistant Or Refractory Acute Lymphoblastic Leukemia
Clinical Trial IDs
- ORG STUDY ID:
IRB # 830049; UPCC #12418
- NCT ID:
NCT03620058
Conditions
- Chemotherapy Resistant Acute Lymphoblastic Leukemia
- Refractory Acute Lymphoblastic Leukemia
Interventions
Drug | Synonyms | Arms |
---|
CART22-65s cells | | CART22-65s in combination with huCART19 |
huCART19 Cells | | CART22-65s in combination with huCART19 |
Purpose
This is a single center, open-label, phase 1 study to determine the safety and feasibility of
infusing CART22-65s with or without huCART19 after administration of lymphodepleting
chemotherapy in adult patients with relapsed or refractory B-ALL.
Trial Arms
Name | Type | Description | Interventions |
---|
CART22-65s monotherapy | Experimental | | |
CART22-65s in combination with huCART19 | Experimental | | - CART22-65s cells
- huCART19 Cells
|
Eligibility Criteria
Inclusion Criteria:
- 1. Patients with relapsed or refractory B cell ALL:
a. Patients with 2nd or greater relapse or refractory to 1st salvage as defined by: i.
Recurrent disease in the bone marrow identified morphologically, by immunohistochemistry or
by Flow cytometry.
ii. Patients with extramedullary relapse only (no bone marrow involvement) will be eligible
if disease response can be assessed radiographically b. Patients with refractory disease as
defined by: i. Failure to achieve remission (<5% bone marrow blasts) after 2 cycles of
induction chemotherapy ii. Patients that achieve remission but remain MRD+ after ≥2 cycles
of induction chemotherapy.
c. Patients with Ph+ ALL are eligible provided they are intolerant to or have failed
tyrosine kinase inhibitor therapy.
d. Patients with prior or current history of CNS3 disease* will be eligible only if CNS
disease is responsive to therapy.
i. *CNS disease definitions:
1. CNS1 - no blasts seen on cytocentrifuge (CNS negative);
2. CNS2 - total nucleated cell count <5x106/L, but blasts seen on cytocentrifuge;
3. CNS3 - total nucleated cell count 5x106/L with blasts on cytocentrifuge and/or signs
of CNS leukemia (i.e. cranial nerve palsy).
- 2. For Cohort 1: Documentation of CD22 expression on malignant cells at relapse.
For Cohort 2: Documentation of CD22 and/or CD19
- 3. Adequate vital organ function defined as:
1. Creatinine ≤ 1.6 mg/dl
2. ALT/AST ≤ 3x upper limit of normal range
3. Total or Direct bilirubin ≤ 2.0 mg/dl. If Total bilirubin is ≤2.0, Direct
bilirubin does not need to be assessed.
4. Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA
- 4. Male or female age ≥ 18 years.
- 5. ECOG Performance Status that is either 0 or 1.
- 6. No contraindications for leukapheresis.
- 7. Subjects of reproductive potential must agree to use acceptable birth control
methods.
Exclusion Criteria:
- 1. Active hepatitis B or active hepatitis C.
- 2. HIV Infection.
- 3. Class III/IV cardiovascular disability according to the New York Heart Association
Classification.
- 4. Subjects with clinically apparent arrhythmia or arrhythmias who are not stable on
medical management within two weeks of eligibility confirmation by
physician-investigator.
- 5. Active acute or chronic graft-versus-host disease (GVHD) requiring systemic
therapy.
- 6. Planned concurrent treatment with systemic steroids or immunosuppressant
medications. Patients may be on a stable low dose of steroids (<10mg equivalent of
prednisone) for chronic respiratory conditions or adrenal insufficiency. For
additional details regarding use of steroid and immunosuppressant medications.
- 7. CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that
might increase the risk of CNS toxicity.
- 8. Pregnant or nursing (lactating) women.
- 10. Patients with a known history or prior diagnosis of optic neuritis or other
immunologic or inflammatory disease affecting the central nervous system.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Assess the safety of CART22-65s in ALL subjects using the common terminology criteria of adverse events (CTCAE) v5.0. |
Time Frame: | 15 months |
Safety Issue: | |
Description: | Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS). |
Secondary Outcome Measures
Measure: | Tumor response. |
Time Frame: | 28 Days |
Safety Issue: | |
Description: | Overall Complete Remission Rate (ORR) at Day 28 and duration of remission |
Measure: | CAR T cell kinetics |
Time Frame: | 1 Year |
Safety Issue: | |
Description: | Engraftment and persistence in blood by qPCR (or flow cytometry) |
Measure: | Evaluate bioactivity of CAR T cells |
Time Frame: | 15 months |
Safety Issue: | |
Description: | Measure levels of systemic soluble immune and inflammatory factors by Luminex-based analyses |
Measure: | Determine antigen expression and normal B cell levels in response to CAR T cells |
Time Frame: | 15 months |
Safety Issue: | |
Description: | Measure CD22, CD19 and B cell levels pre- and post-CAR T cell infusion by flow cytometry |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | University of Pennsylvania |
Last Updated
June 29, 2021