Safety and Efficacy of CMD03 CAR T Cell in Children With Relapse or Refractory Solid Tumors

ConditionsPediatric Cancers Solid Tumor Pediatric

Trial statusRecruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexAll

Age1-25

SponsorChulalongkorn University

About this trial

A Phase 1 clinical trial to evaluate the safety and early efficacy of CAR T-cells with IL-7Ra signal targeting B7H3 in children with solid tumors patients after complete standard treatments.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Participants must have B7-H3 positive solid tumor with measurable disease.

Evidence of relapsed or refractory disease after standard first-line therapy

Age 1 - 25 years

Sex: Male or female

Disqualifiers

Presence of greater than or equal to grade 3 cardiac dysfunction or symptomatic arrythmia requiring intervention

Presence of primary immunodeficiency or bone marrow failure syndrome

Presence of uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities, or psychiatric illness/social situations that would limit compliance with study requirements

Pregnant or breastfeeding women were excluded from this study because CAR-T cell therapy may be associated with the potential for teratogenic or abortifacient effects. Women of childbearing potential must have a negative serum pregnancy test. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CAR-T cells, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study. Participants of childbearing or child-fathering potential must be willing to practice birth control from the time of enrollment in this study and for four months after receiving CAR-T-cell infusion.

Trial design

Design model

Single group

Treatments tested in this trial

B7H3-IL7Ra CAR-T cells
Biological/Vaccine
Autologous T cells lentiviral transduced to express a B7H3-specific chimeric antigen receptor (CAR) with the addition of an IL-7 receptor alpha signaling domain, administered via central venous access catheter after lymphodepletion

Treatment groups

9 Participants

are divided into 1 treatment group

Group A: B7H3/IL-7Ra CAR T cell in Solid tumorsExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

Safety and tolerability of B7H3-IL7Ra CAR T cells infusion in solid tumors patients.

The incidence of adverse events assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0

Time frame

7 days, 14 days, 21 days, 30 days, 60 days, 90 days, 6 months and 12 months after B7H3-IL7Ra CAR-T cell infusion

Secondary outcomes

The overall response rate of solid tumors

The overall response rate will be assessed using radiologic response criteria that use the standard sum of the two longest 2D perpendicular diameters to distinguish stable disease, progressive disease (\>25% increase), partial response (\>50% decrease), and complete response (no evaluable or measurable disease).

Time frame

1, 3, 6, and 12 months after B7H3-IL7Ra CAR-T cell infusion

Other outcomes

The persistence and distribution of B7H3-IL7Ra CAR T cells in the peripheral blood

The persistence and distribution of B7H3-IL7Ra CAR T cells in the peripheral blood of relapsed/refractory pediatric solid tumor patients will be measured by flow cytometry.

Time frame

7 days, 14 days, 21 days, 30 days, 60 days, 90 days, 6 months and 12 months after B7H3-IL7Ra CAR-T cell infusion

Serum cytokine level measurement

Serum cytokine level measurement including IL-2,IL-4, IL-6, IL-10, TNF-alpha and IFN-gamma before and after B7-H3-IL7Ra CAR T-cell infusion

Time frame

7 days, 14 days, 21 days and 30 days after B7H3-IL7Ra CAR-T cell infusion