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Hypofractionated Radiation in Combination With B7-H3-CAR T Cells for Pediatric Patients With Relapsed/Refractory Sarcomas

ConditionsSarcomaChildhood OsteosarcomaChildhood RhabdomyosarcomaChildhood Soft Tissue SarcomaEwing Sarcoma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
AgeUp to 21
SponsorSt. Jude Children's Research Hospital

About this trial

RAD3CAR is a phase I study designed to evaluatethe safety of B7-H3-CAR T cells and lymphodepletion in combination with hypofractionated radiation therapy.

Primary objective:

\- To evaluate the safety of B7-H3-CAR T cell therapy after priming with hypofractionated radiation therapy (HFRT) and lymphodepleting chemotherapy in patients ≤ 21 years of age with relapsed/refractory B7-H3+ sarcomas.

Secondary objectives:

* To describe the antitumor activity of B7-H3-CAR T cells in combination with HFRT * To determine if B7-H3-CAR T cells traffic to tumor sites after combination treatment with HFRT

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≤ 21 years old

B7-H3+ sarcoma; B7-H3 expression will be evaluated by standard immunohistochemistry (IHC) using any previously obtained biopsy; a tumor is considered B7-H3 positive with a H score greater than or equal to 100

Osteosarcoma

Ewing Sarcoma

Disqualifiers

Known primary immunodeficiency

Known HIV positivity

Severe, uncontrolled intercurrent bacterial, viral, or fungal infection

Known active malignancy other than the B7-H3+ sarcoma being treated on study

Trial design

Design model

Single group

Treatments tested in this trial

  • Fludarabine

    Drug

    Intravenously on day -5, -4, -3 and -2

  • Cyclophosphamide

    Drug

    Intravenously on day -3, -2

  • B7-H3-CAR T Cells

    Drug

    Intravenously on day 0

  • Radiation Therapy

    Radiation

    5 or 8 treatment sessions (fractions), scheduled to complete on Day -2

Treatment groups

42 Participants
are divided into 1 treatment group
Group A: RAD3CAR TreatmentExperimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

Dose limiting toxicity (DLT) rate

Proportion of evaluable participants experiencing DLTs

Time frame
up to 4 weeks after CAR T cell infusion
2

Incidence of adverse events (AEs)

AEs will be assessed and graded using CTCAE v5.0, except for cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS), which will be graded according to ASTCT consensus guidelines. AEs will be summarized and reported descriptively

Time frame
up to 4 weeks after CAR T cell infusion

Secondary outcomes

1

Clinical antitumor activity

Best overall response after treatment as determined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and if applicable bone marrow evaluation

Time frame
4-12 weeks after CAR T cell infusion
2

B7-H3-CAR T cell trafficking to tumor sites

Evaluate for the presence of B7-H3-CAR T cells in post-treatment tumor biopsies

Time frame
2 weeks after CAR T cell infusion

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

St. Jude Children's Research Hospital

Lead sponsor

Source ClinicalTrials.gov
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