Trial Title:
CD7-CAR-T Cells in Pediatric Relapsed/Refractory CD7+ T-ALL/LL
NCT ID:
NCT06064903
Condition:
T-Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma
Conditions: Official terms:
Lymphoma
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Conditions: Keywords:
T-ALL
T-LL
Relapsed
Refractory
anti-CD7 PEBL-CAR T
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
CD7-CART01
Description:
A single IV infusion of CD7-CART01 on Day 0
Arm group label:
CD7-CART01
Summary:
The main purpose of this study is to evaluate the safety, to establish the recommended
dose, and to evaluate the antitumor effect of CD7-CART01 in pediatric patients with
relapsed or refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL) or lymphoblastic
lymphoma (T-LL).
Detailed description:
This is an in-human, open-lable, single-arm, single-agent, Phase 1/2 study in pediatric
patients with R/R T-ALL/T-LL who have failed at least one standard frontline chemotherapy
or relapsed after allogeneic hematopoietic stem cell transplantation (HSCT). The study
will consist of two phases, Phase 1 and Phase 2. During the Dose Escalation portion of
the trial (Phase 1) up to 12 patients will receive CD7-CART01, in up to 2 dose levels
until maximum tolerated dose (MTD) is determined. If 2 DLTs are observed in the dose
level 1 an additional DL0 will be explored. The dose escalation phase will enroll
successive cohorts of 3 up to 6 patients guided by a standard dose-finding 3 + 3 design.
Once the recommended phase 2 dose (RP2D) is defined, the phase 2 portion of the study
will enroll at the MTD/RD identified in the phase I up to 26 pediatric patients (for both
phases) and the study protocol will be amended to include additional, international
centers.
Criteria for eligibility:
Criteria:
Procurement eligibility
Inclusion Criteria:
1. Diagnosis of CD7 expressing (> 98% CD7 expression on blast cells) T-ALL or LL and
one of the following:
1. Patients in 1st or subsequent relapse, after at least one standard frontline
chemotherapy with BM involvement (MRD >1% in 2 consecutive determinations or
evidence of morphological relapse, i.e. >5% blasts in BM);
2. Relapse after allogeneic HSCT, if at least 100 days post-transplant, if there
is no evidence of active GVHD and if the patient is no longer taking
immunosuppressive agents for at least 30 days prior to enrollment;
3. CNS disease as defined as > 5 WBCs/mcL in CSF with morphological/flow-cytometry
evidence of blasts or biopsy proven recurrence in the eye or brain;
4. Extramedullary relapse as defined by morphological evidence of blasts in the
testis or any other extramedullary sites;
5. Refractory disease, defined as MRD ≥ 1% or <1% but persistently positive (i.e.
a positive MRD value confirmed by PCR at 2 subsequent evaluations performed at
least 2 weeks apart), at the end of consolidation blocks in newly diagnosed
patients;
2. Age: 6 months - 25 years.
3. Adequate venous access for apheresis or eligible for appropriate catheter placement,
and no other contraindications for leukapheresis.
4. Voluntary informed consent is given. For subjects <18-year-old, or below the age
required by each Country regulation, their legal guardian must give informed
consent. Pediatric subjects will be included in age-appropriate discussion and
verbal assent will be obtained for those greater than or equal to 12 years of age,
when appropriate, or to sign age-adapted informed consent, according to the
regulatory requirement of each Country.
5. Clinical performance status: Patients > 16 years of age: Karnofsky greater than or
equal to 60%; Patients < 16 years of age: Lansky scale greater than or equal to 60%.
Exclusion Criteria:
1. Severe, uncontrolled active intercurrent infections.
2. HIV, or active HCV and/or HBV infection.
3. Blast contamination in peripheral blood >5%, by flow-cytometry, at the time of
leukapheresis collection.
4. Concurrent or recent prior therapies, before apheresis:
1. Systemic steroids (at a dose equivalent to or greater than 2 mg/kg prednisone)
in the 2 weeks before apheresis collection. Recent or current use of
inhaled/topical/non-absorbable steroids is not exclusionary
2. Systemic chemotherapy in the 2 weeks preceding apheresis collection
3. Nelarabine, daratumomab, clofarabine exposure in the 3 weeks preceding
apheresis collection
4. Anti-thymocyte globulin (ATG) or Alemtuzumab (Campath®) in the 8 weeks
preceding apheresis collection
5. Immunosuppressive agents in the 2 weeks preceding apheresis collection
6. Radiation therapy must have been completed at least 2 weeks prior to apheresis
7. Other anti-neoplastic investigational agents currently administered or within
30 days prior to apheresis (i.e. start of protocol therapy)
8. Exceptions:
- There is no time restriction with regard to prior intrathecal
chemotherapy, provided that there is complete recovery from any acute
toxic effects of such chemotherapy;
- Patients who relapse while receiving standard ALL maintenance chemotherapy
will not be required to have a waiting period before entry onto this study
provided they meet all other eligibility criteria;
- Subjects receiving steroid therapy at physiologic replacement doses only
are allowed provided there has been no increase in dose for at least 2
weeks prior to starting apheresis.
Treatment eligibility
Inclusion criteria:
1. Diagnosis of CD7 expressing (> 98% CD7 expression on blast cells) T-ALL or LL and
one of the following:
1. Patients in 1st or subsequent relapse, after at least one standard frontline
chemotherapy with BM involvement (MRD >1% in 2 consecutive determinations or
evidence of morphological relapse, i.e. >5% blasts in BM)
2. Relapse after allogeneic HSCT, if at least 100 days post-transplant, if there
is no evidence of active GVHD and if the patient is no longer taking
immunosuppressive agents for at least 30 days prior to enrollment
3. CNS disease as defined as > 5 WBCs/mcL in CSF with morphological or
flow-cytometry evidence of blasts or biopsy proven recurrence in the eye or
brain
4. Extramedullary relapse as defined by morphological evidence of blasts in the
testis or any other extramedullary sites
5. Refractory disease, defined as MRD ≥1% or <1% but persistently positive (i.e. a
positive MRD value confirmed by PCR at 2 subsequent evaluations performed at
least 2 weeks apart), at the end of consolidation blocks in newly diagnosed
patients
2. Measurable or evaluable disease at the time of enrollment, which may include any
evidence of disease, including MRD detected by flow-cytometry, cytogenetics, or
polymerase chain reaction (PCR) analysis.
3. Age: 6 months - 25 years.
4. Before enrollment for treatment, patients must have a potential allogeneic
hematopoietic stem cell (HSC) donor (matched related, matched unrelated or
haploidentical) available.
5. Voluntary informed consent is given. For subjects <18-year-old, or below the age
required according to each Country regulation, their legal guardian must give
informed consent. Pediatric subjects will be included in age-appropriate discussion
and verbal assent will be obtained for those greater than or equal to 12 years of
age, when appropriate, or to sign age-adapted informed consent, according to the
regulatory requirement of the Country.
6. Clinical performance status: Patients > 16 years of age: Karnofsky greater than or
equal to 60%; Patients < 16 years of age: Lansky scale greater than or equal to 60%.
Exclusion criteria:
1. Pregnant or lactating women.
2. Severe, uncontrolled active intercurrent infections.
3. HIV, or active HCV and/or HBV infection.
4. Life-expectancy < 6 weeks.
5. Hepatic function: Inadequate liver function defined as total bilirubin > 4x upper
limit of normal (ULN) or transaminase (ALT and AST) > 6 x ULN.
6. Renal function: serum creatinine > 3x ULN for age.
7. Blood oxygen saturation < 90%.
8. Cardiac function: Left ventricular ejection fraction lower than 45% by ECHO.
9. Congestive heart failure, 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.
10. Uncontrolled seizures or status epilepticus; increased intra-cranial pressure as
evidenced by papilledema and CSF opening pressure > 20 cm water; decreased conscious
state (any cause).
11. Contamination of either the apheresis collection or the CD7-CART01 drug product with
>5% blasts.
12. Presence of active, grade 2-4 acute or extensive chronic GvHD.
13. Concurrent or recent prior therapies, before infusion:
1. Systemic steroids (at a dose > 2 mg/kg prednisone) in the 2 weeks before
infusion. Recent or current use of inhaled/topical/non-absorbable steroids is
not exclusionary
2. Systemic chemotherapy in the 2 weeks preceding infusion
3. Anti-thymocyte globulin (ATG) or Alemtuzumab (Campath®) in the 8 weeks
preceding infusion
4. Immunosuppressive agents in the 2 weeks preceding infusion
5. Radiation therapy must have been completed at least 3 weeks prior to enrollment
6. Other anti-neoplastic investigational agents currently administered or within
30 days prior to infusion (i.e., start of protocol therapy)
7. Exceptions:
- There is no time restriction in regards to prior intrathecal chemotherapy
but there must be a complete recovery from any acute toxic effects from
such chemotherapy;
- Patients who relapse while receiving standard ALL maintenance chemotherapy
will not be required to have a waiting period before entry onto this study
provided that they meet all other eligibility criteria;
- Subjects receiving steroid therapy at physiologic replacement doses only
are allowed provided that there has been no increase in dose for at least
2 weeks prior to starting apheresis.
Gender:
All
Minimum age:
6 Months
Maximum age:
25 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Ospedale Pediatrico Bambino Gesù
Address:
City:
Rome
Zip:
00165
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Franco Locatelli, MD PhD
Phone:
066859
Phone ext:
2678
Email:
franco.locatelli@opbg.net
Contact backup:
Last name:
Francesca Del Bufalo, MD PhD
Phone:
066859
Phone ext:
2739
Email:
francesca.delbufalo@opbg.net
Investigator:
Last name:
Franco Locatelli, MD PhD
Email:
Principal Investigator
Start date:
April 21, 2024
Completion date:
September 30, 2040
Lead sponsor:
Agency:
Bambino Gesù Hospital and Research Institute
Agency class:
Other
Source:
Bambino Gesù Hospital and Research Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06064903
