Description:
Background:
- One type of cancer therapy takes blood cells from a person, changes them in a lab, then
gives the cells back to the person. In this study, researchers are using an anti-CD22 gene, a
virus, and an immune receptor to change the cells.
Objective:
- To see if giving anti-CD22 Chimeric Antigen Receptor (CAR) cells to young people with
certain cancers is safe and effective.
Eligibility:
- People ages 1-39 with a leukemia or lymphoma that has not been cured by standard therapy.
Design:
- Participants will be screened to ensure their cancer cells express the CD22 protein.
They will also have medical history, physical exam, blood and urine tests, heart tests,
scans, and x-rays. They may give spinal fluid or have bone marrow tests.
- Participants may have eye and neurologic exams.
- Participants will get a central venous catheter or a catheter in a large vein.
- Participants will have white blood cells removed. Blood is removed through a needle in
an arm. White blood cells are removed. The rest of the blood is returned by needle in
the other arm.
- The cells will be changed in a laboratory.
- Participants will get two IV chemotherapy drugs over 4 days. Some will stay in the
hospital for this.
- All participants will be in the hospital to get anti-CD22 CAR cells through IV. They
will stay until any bad side effects are gone.
- Participants will have many blood tests. They may repeat some screening exams.
- Participants will have monthly visits for 2-3 months, then every 3-6 months. They may
repeat some screening exams.
- Participants will have follow-up for 15 years.
Title
- Brief Title: Anti-CD22 Chimeric Receptor T Cells in Pediatric and Young Adults With Recurrent or Refractory CD22-expressing B Cell Malignancies
- Official Title: Phase I Dose Escalation Study of Anti-CD22 Chimeric Receptor T Cells in Pediatric and Young Adults With Recurrent or Refractory CD22-expressing B Cell Malignancies
Clinical Trial IDs
- ORG STUDY ID:
150029
- SECONDARY ID:
15-C-0029
- NCT ID:
NCT02315612
Conditions
- Follicular Lymphoma
- ALL
- NHL
- Large Cell Lymphoma
Interventions
Drug | Synonyms | Arms |
---|
CD22-CAR | | Arm 1 |
Purpose
Background:
- One type of cancer therapy takes blood cells from a person, changes them in a lab, then
gives the cells back to the person. In this study, researchers are using an anti-CD22 gene, a
virus, and an immune receptor to change the cells.
Objective:
- To see if giving anti-CD22 Chimeric Antigen Receptor (CAR) cells to young people with
certain cancers is safe and effective.
Eligibility:
- People ages 1-39 with a leukemia or lymphoma that has not been cured by standard therapy.
Design:
- Participants will be screened to ensure their cancer cells express the CD22 protein.
They will also have medical history, physical exam, blood and urine tests, heart tests,
scans, and x-rays. They may give spinal fluid or have bone marrow tests.
- Participants may have eye and neurologic exams.
- Participants will get a central venous catheter or a catheter in a large vein.
- Participants will have white blood cells removed. Blood is removed through a needle in
an arm. White blood cells are removed. The rest of the blood is returned by needle in
the other arm.
- The cells will be changed in a laboratory.
- Participants will get two IV chemotherapy drugs over 4 days. Some will stay in the
hospital for this.
- All participants will be in the hospital to get anti-CD22 CAR cells through IV. They
will stay until any bad side effects are gone.
- Participants will have many blood tests. They may repeat some screening exams.
- Participants will have monthly visits for 2-3 months, then every 3-6 months. They may
repeat some screening exams.
- Participants will have follow-up for 15 years.
Detailed Description
Background:
- Adoptive cellular therapy with T cells genetically modified using viral-based vectors to
express chimeric antigen receptors targeting the CD19 molecule have demonstrated
dramatic clinical responses in patients with acute lymphoblastic leukemia (ALL).
However, not all patients respond and CD19-negative escape has been observed following
CD19 CAR therapy, as well as anti-CD19/CD3 bispecific antibody therapy. Thus, additional
targets are needed.
- CD22 is a B-lineage-restricted, transmembrane phosphoglycoprotein of the Ig superfamily
that is widely expressed on B-cell malignancies including 96% to 100% of pediatric
Bprecursor ALL. Therefore, CD22 represents a promising target. Encouraging responses
targeting CD22 with an antibody based immunoconjugate have been seen in patients,
including children, with recurrent and refractory ALL. This will be the first in human
testing of anti-CD22 CAR adoptive cell therapy.
Objectives:
- To determine the feasibility of producing anti-CD22 CAR cells meeting established
release criteria. Complete
- To assess the safety of administering escalating doses of anti-CD22-CAR engineered T
cells in children and young adults with recurrent or refractory CD22- expressing B cell
malignancies following a cyclophosphamide/fludarabine preparative regimen.
Eligibility:
- Patients 3-39 years of age, at least 14.5 kg, with CD22-expressing B-cell malignancies that
have recurred after or not responded to one or more standard regimens and deemed incurable by
standard therapy. Patients with a history of allogeneic hematopoietic transplantation (SCT)
who meet all eligibility criteria are eligible to participate. Patients previously treated
with anti-CD19 CAR engineered T cells are also eligible.
Design:
- PBMC will be obtained by leukapheresis, CD3+ cells enriched and cultured in the presence
of anti-CD3/-CD28 beads followed by lentiviral vector supernatant containing the
anti-CD22 (M971BBz) CAR.
- On Day -4 (cell infusion is Day 0), patients will begin induction chemotherapy
comprising fludarabine 25 mg/m2 on Days -4, -3 and -2 and cyclophosphamide 900 mg/m2 on
day 2.
- The CD22-CAR cells will be infused on Day 0, with up to a 72h delay allowed for infusion
of fresh cells or a 7 day delay if cells are cryopreserved, if needed for resolution of
clinical toxicities, to generate adequate cell numbers, or to facilitate scheduling.
- A phase I cell dose escalation scheme will be performed using 3 dose levels (3 x 10(5)
transduced T cells/kg; 1 x 10(6) transduced T cells/kg; and 3 x 10(6) transduced T
cells/kg;). If 2/6 patients have DLT at dose level 1, safety will be evaluated in a
de-escalated dose of 1 x 10(5) transduced T cells/kg (more or less 20%)). Once the
maximum tolerated dose (or highest level evaluated) is reached, enrollment into an
expansion cohort of a total of 83 patients at MTD will proceed to provide additional
information regarding the feasibility, safety and efficacy of this treatment.
- Patients will be monitored for toxicity, response and T cell persistence as well as
other biologic correlates.
Trial Arms
Name | Type | Description | Interventions |
---|
Arm 1 | Experimental | Dose escalation of CD22-CAR | |
Arm 2 | Experimental | Dose expansion of CD22-CAR | |
Eligibility Criteria
-INCLUSION CRITERIA:
1. Patient must have a B cell ALL (inclusive of ALL blast transformation from CML) or
lymphoma and must have relapsed or refractory disease after at least one standard
chemotherapy regimen and one salvage regimen. In view of the PI and the primary
oncologist, there must be no available alternative curative therapies and subjects
must be either ineligible for allogeneic stem cell transplant (SCT), have refused SCT,
recurred after SCT, or have disease activity that prohibits SCT at the time of
enrollment.
2. CD22 expression must be detected on greater than 15% of the malignant cells by
immunohistochemistry or greater than 80% by flow cytometry. The choice of whether to
use flow cytometry or immunohistochemistry will be determined by what is the most
easily available tissue sample in each patent. In general, immunohistochemistry will
be used for lymph node biopsies, flow cytometry will be used for peripheral blood and
bone marrow samples and CSF when feasible.
3. Patients must have measurable or evaluable disease at the time of enrollment, which
may include any evidence of disease including minimal residual disease detected by
flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis.
4. Greater than or equal to 3 years of age (and at least 14.5 kg) and less than or equal
to 39 years of age at time of enrollment.
5. Subjects with CNS disease are eligible, with exceptions as noted in the exclusion
criteria
6. Patients, parents/guardian(s), legally authorized representative (LAR), or durable
power of attorney must be able to give consent and sign the informed consent document.
7. Clinical performance status: Patients greater than or equal to 16 years of age:
Karnofsky greater than or equal to 50%; Patients < 16 years of age: Lansky scale
greater than or equal to 50%. Subjects who are unable to walk because of paralysis,
but who are upright in a wheelchair will be considered ambulatory for the purpose of
calculating the performance score.
8. Patients of child-bearing or child-fathering potential must be willing to practice
birth control from the time of enrollment on this study and for four months after
receiving the preparative regimen.
9. Patients must have adequate organ function as described below:
-Cardiac function: Left ventricular ejection fraction greater than or equal to 45% or
fractional shortening greater than or equal to 28%.
-Pulmonary function: Patients without respiratory symptoms (e.g. dyspnea at rest,
known requirement for supplemental oxygen therapy) and who have an oxygen saturation
greater than or equal to 92% on room air, will be eligible. For patients not meeting
this criteria, pulmonary function tests will be performed to confirm that the
DLCO/VA/Adj is 50% of the normal predicted value corrected for hemoglobin and alveolar
volume in order to meet eligibility.(For children who are unable to cooperate for
PFTs, the criterion is: No evidence of dyspnea at rest, no exercise intolerance and no
requirement for supplemental oxygen therapy. )
- Hematologic function:
--Absolute neutrophil count greater than or equal to 750/mcL
--Platelets greater than or equal to 50,000/mcl
- A subject will not be excluded because of pancytopenia related to disease
- Liver Function:
- AST (SGOT)/ALT (SGPT): less than or equal to 20 x institutional upper limit
of normal
- Total bilirubin less than or equal to 2 x ULN (ecept in the case of subjects
with documented Gilbert s disease greater than or equal to 3 x ULN)
- Renal Function: Normal creatinineCreatinine level < the maximum for age listed in
the table below OR creatinine clearance greater than or equal to 60 mL/min/1.73
m2 for patients with creatinine levels above institutional normal.
- less than or equal to 5 years old: maximum serum creatinine 0.8mg/dL
- between 6 and 10 years old: maximum serum creatinine 1.0mg/dL
- greater than 10 years old: maximum serum creatinine 1.2mg/dL
10. Patients previously treated with anti-CD19 CAR or other adoptive cell therapies will
be eligible if all other eligibility criteria in the expansion phase. Circulating CAR
T cells must be <5% in peripheral blood.
EXCLUSION CRITERIA:
Subjects meeting any of the following criteria are not eligible for participation in the
study:
1. Subjects with radiologically-detected active CNS lymphoma, leptomeningeal CNS disease or
isolated CNS disease which are eligible for definitive CNS directed radiationtherapy will
be excluded.
2 .Hyperleukocytosis (greater than or equal to 50,000 blasts/ L) or rapidly progressive
disease that in theestimation of the investigator and sponsor would compromise ability to
complete study therapy;
3. Pregnant or breast-feeding females
4. Recent prior therapy
5. Subjects will be excluded related to the following prior therapy criteria:
- Systemic chemotherapy, anti-neoplastic investigational agents, or antibody based
therapies 2 weeks (6 weeks for clofarabine or nitrosoureas) prior to apheresis with
the following exception:
--No time restriction with prior intrathecal chemotherapy, steroid therapy,
hydroxyurea or ALL maintenance type chemotherapy (vincristine, 6-mercaptopurine, oral
methotrexate, or a tyrosine kinase inhibitor for patients with Ph+ ALL) provided there
is recovery from any acute toxic effects.
- Radiation therapy <= 3 weeks prior to apheresis with the following exception:
--No time restriction with radiation therapy if the volume of bone marrow treated is
less than 10% and the subject has measurable/evaluable disease outside the radiation
window.
- History of allogeneic stem cell transplantation prior to apheresis that meet the
following criteria:
- Less than 100 days post-transplant
- Evidence of active graft-versus-host disease (GVHD)
- Taking immunosuppressive agents within 30 days prior to apheresis.
- Less than 6 weeks post donor lymphocyte infusion (DLI)
- History of prior CAR therapy or other adoptive cell therapies prior to apheresis that
meet the following criteria:
- Less than 30 days post-infusion
- Circulating CAR T cells (or genetically modified cells) >=5% by flow cytometry in
peripheral blood
6. HIV/HBV/HCV Infection:
1. Seropositive for HIV antibody. (Patients with HIV are at increased risk of
lethal infections when treated with marrow-suppressive therapy. Appropriate
studies will beundertaken in patients receiving combination antiretroviral
therapy in the future should study results indicate effectiveness.)
2. Positive for Hepatitis B surface antigen (HbsAG)
3. Evidence of active HCV (evidenced by detectable HCV RNA)
7. Uncontrolled, symptomatic, intercurrent illness including but not limited
to infection, congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, psychiatric illness, or social situations that would limit
compliance with study requirements or in the opinion of the PI would pose an
unacceptable risk to the subject;
8. Second malignancy other than in situ carcinoma of the cervix, unless the
tumor was treated with curative intent at least two years previously and
subject is in remission;
9. History of severe, immediate hypersensitivity reaction attributed to
compounds of similar chemical or biologic composition to any agents used in
study or in the manufacturing of the cells (i.e. gentamicin)
Maximum Eligible Age: | 39 Years |
Minimum Eligible Age: | 3 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Toxicity |
Time Frame: | End of treatment |
Safety Issue: | |
Description: | Number of patients who have grade 3 CRS and above |
Secondary Outcome Measures
Measure: | Safety and Toxicity |
Time Frame: | 1 month, 3 months and 6 months following CAR infusion |
Safety Issue: | |
Description: | Number of patients who have detectable CAR cells |
Measure: | Objective Response (Complete + Partial Remission) |
Time Frame: | 1 month, 3 months and 6 months following CAR infusion |
Safety Issue: | |
Description: | The number of patients who have complete and partial remissions |
Measure: | CAR-T cell Persistence |
Time Frame: | 1 month, 3 months and 6 months following CAR infusion |
Safety Issue: | |
Description: | The number of patients who have detectable CAR cells |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | National Cancer Institute (NCI) |
Trial Keywords
- CD-22 Expressing Tumor
- Chimeric Antigen Receptor
- Adoptive Immunotherapy
- ALL
- Lymphoma
Last Updated
August 31, 2021