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B7-H3.CD28Z.CART in Solid Tumors

ConditionsPediatric Solid TumorNeuroblastoma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age9-30
SponsorRobbie Majzner

About this trial

The goal of this research study is to test if a new cell therapy (B7-H3.CD28Z.CART / B7-H3 CAR T cells) is safe and effective in treating children and young adults with solid cancers whose tumors have returned or stopped responding to standard treatments (relapsed or refractory) and have been identified with a B7-H3 marker.

The names of the treatment interventions used in this study are:

* B7-H3.CD28Z.CART / B7-H3 CAR T cells * Fludarabine * Cyclophosphamide

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Participants must have histologically confirmed diagnosis of a solid tumor that is relapsed or refractory for which standard curative measures do not exist or are no longer effective.

Participant must have adequate pre-trial tumor material available to determine B7-H3 status. Tumor tissue from the most recent resection or biopsy of recurrent disease is preferred. If unavailable, tumor tissue from prior recurrences or from the time of initial diagnosis is acceptable.

Age >=9 months and <30 years.

Lansky/Karnofsky performance status ≥50% (see Appendix A)

Disqualifiers

Participants who are receiving any other investigational agents.

Participants with known current brain metastases or leptomeningeal disease. Prior CNS metastatic disease is allowable if prior resection and/or radiation occurred at least 8 weeks prior to enrollment, without any intervening CNS metastasis, progression or recurrence, and participants are clinically stable as evidenced by no requirements for corticosteroids, no evolving neurologic deficits, and no progression of residual brain abnormalities.

Participants with any prior immunodeficiency or history of autoimmune disease requiring systemic steroids/ immunosuppressive medication/ disease modifying agents within the last 2 years

Prior solid organ transplant. Prior allogeneic or autologous stem cell transplant is permitted as outlined in Section 3.2.

Trial design

Design model

Sequential

Treatments tested in this trial

  • B7-H3.CD28Z.CART

    Biological/Vaccine

    Modified autologous T cells administered via Intravenous (IV) infusion

  • Fludarabine

    Drug

    Administered intravenously

  • Cyclophosphamide

    Drug

    Administered intravenously

Treatment groups

40 Participants
are divided into 1 treatment group
Group A: DOSE ESCALATION B7-H3.CD28Z.CART CELL TherapyExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Manufacturing Success Rate of Autologous B7-H3.CD28Z CART Cells

Each participant's product will be tested for the following criteria: cell viability ≥ 70%; cell number within ± 20% of the planned dose; CD3+ T cells ≥ 80% of leukocytes; CAR-positive cells ≥ 10% of CD3+ T cells; endotoxin ≤ 5 EU/kg; mycoplasma not detected; vector copy number (VCN) per transduced cell ≤ 10; replication-competent retrovirus (RCR) not detected; and sterility confirmed as "No Growth to Date" (NGTD) after a minimum of 5 days in culture. A participant will be classified as a manufacturing success if the final product satisfies all release criteria. If any criterion is not met, the participant will be classified as a manufacturing failure. The manufacturing success rate is defined as the proportion of participants classified as a success.

Time frame
Participants will receive the CART cell infusion on Day 0.
2

Maximum Tolerated Dose (MTD) of B7-H3.CD28Z.CART Cells

The MTD is defined as the highest dose level of B7-H3.CD28Z.CART cells at which the rate of dose-limiting toxicity (DLT) is acceptable per the modified 3+3 design. The recommended phase 2 dose (RP2D) is the MTD of single-agent autologous B7-H3.CD28Z.CART cells. Additional details are provided in Protocol Section 13.1.

Time frame
28 days

Secondary outcomes

1

Number of Participants Experience Dose-Limiting Toxicity (DLT)

Any ≥ grade 3 adverse event per Common Terminology Criteria for Adverse Events (CTCAE v6) within 28 days of initial B7-H3.CD28Z.CART infusion that is at least possibly related to the product is a Dose-Limiting Toxicity (DLT).

Time frame
28 days
2

Adverse Events of Special Interest (AESI) Rate on the First Infusion

The AESI rate is defined as the proportion of participants experiencing at least one adverse event meeting the AESI criteria during the protocol-specified adverse event reporting period. The definition of AESI are defined in protocol section 7.2.

Time frame
15 years
3

Objective Response Rate (ORR)

ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) during study treatment. Disease assessed per revised International Neuroblastoma Response Criteria (INRC) in participants with relapsed or refractory high-risk neuroblastoma or per RECIST1.1 in participants with other solid tumors.

Time frame
Disease assessments will be performed at Day 28, month 3, and then every 3 months through month 24 or up to month 48, if received second infusion.
4

Median Progression-Free Survival (PFS)

PFS based on Kaplan-Meier method is defined as the time from start of treatment to the earlier of relapse, progression, or death due to any cause. Participants alive without disease relapse or progression are censored at date of last disease evaluation. Disease assessed per revised International Neuroblastoma Response Criteria (INRC) in participants with relapsed or refractory high-risk neuroblastoma or per RECIST1.1 in participants with other solid tumors.

Time frame
Disease assessments will be performed at Day 28, month 3, and then every 3 months through month 24 or up to month 48, if received second infusion.

Other outcomes

Sponsors and contacts

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

Robbie Majzner

Lead sponsor

Dana-Farber Cancer Institute

Sponsor institution

Band of Parents

Collaborator

Source ClinicalTrials.gov
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