B7-H3.CD28Z.CART for Pediatric Solid Tumors
This study is testing a new cell therapy called B7-H3.CD28Z.CART, along with Fludarabine and Cyclophosphamide, for children and young adults (ages 9 months to 30 years) with solid cancers like neuroblastoma. These are cancers that have returned or stopped responding to standard treatments, and also show a specific marker called B7-H3. The B7-H3.CD28Z.CART cells are specially modified blood cells designed to find and help kill cancer cells with this B7-H3 marker. This is the first time these specific B7-H3 CAR T cells are being given to people. The main goals are to see if the B7-H3.CD28Z.CART cells can be successfully made and to find the highest safe dose. Up to 40 participants are planned for this study, but its current status is unclear.
- Study design
- This is a Phase 1, open-label study, meaning everyone knows what treatment is being given. It is a single-center study, and up to 40 participants are expected.
- What's involved
- You would undergo screening for eligibility, which includes checking for the B7-H3 marker. If eligible, procedures include in-clinic visits, blood tests, urine tests, electrocardiograms (ECGs), echocardiograms (ECHOs), and bone marrow biopsies and aspirations.
- Compensation
- Not stated in the trial record.
- Follow-up
- The maximum tolerated dose is measured at 28 days after the B7-H3.CD28Z.CART cell infusion.
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NCT07358260
B7-H3.CD28Z.CART in Solid Tumors
Not Yet Recruiting
PHASE1Ages 9–30InterventionalTreatmentRobbie MajznerInvestigator-initiated
~40 participants
Updated 2026-01-22 on ClinicalTrials.gov
What's tested:B7-H3.CD28Z.CARTFludarabineCyclophosphamide
At a glance
Recruiting sites
0 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Manufacturing Success Rate of Autologous B7-H3.CD28Z CART Cells
Measured over Participants will receive the CART cell infusion on Day 0.
+1 more outcome measured
Conditions
Where it's being run
1 sites across 1 statesMassachusetts1
Study leadership
- Natalie Collins, MD · PRINCIPAL_INVESTIGATOR · Dana-Farber Cancer Institute
Who to contact
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Do you actually qualify for this trial?
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Eligibility criteria
Inclusion
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)
Life expectancy of greater than 12 weeks
Participants who are screened for this trial should be reasonably anticipated to meet the eligibility criteria for enrollment described in Section 3.2 if their tumor is B7-H3-positive.
Ability to understand and/or the willingness of their parent or legally authorized representative to sign a written informed consent document for prescreening.
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.
Participants must have measurable or evaluable disease for dose escalation. For expansion phase, participants with neuroblastoma must have measurable or evaluable disease by INRC. Participants with other solid tumors must have measurable disease by RECIST1.1 for the expansion phase.
B7-H3 expression: Demonstration of B7-H3 expression with H score \>100 by immunohistochemistry (IHC) is required by IHC performed at Boston Children's Hospital. Participants may choose to enroll on the prescreening portion, which allows for assessment of B7-H3 expression only, prior to enrollment on the full clinical trial as described in Section 3.1.
Age \>=12 months and \<30 years.
Lansky/Karnofsky performance status ≥50% (see APPENDIX A: PERFORMANCE STATUS SCALES/SCORES)
Life expectancy of greater than 12 weeks
Prior therapy:
At least 1 week post any small port radiation therapy; at least 6 weeks from large field or other substantial bone marrow irradiation (craniospinal, whole abdomen, total lung, total body irradiation, \>50% marrow).
At least 2 weeks since any prior myelosuppressive chemotherapy
At least 28 days from other investigational antineoplastic or disease-directed agents
At least 7 days from most recent myeloid growth factor, at least 14 days must have elapsed after receipt of pegfilgrastim.
At least 7 days from prior biologic antineoplastics, tyrosine kinase inhibitor, targeted agent or metronomic non-myelosuppressive chemotherapy.
At least 21 days or 5 half-lives, whichever is shorter, post any treatment with monoclonal antibodies (including checkpoint inhibitors and bevacizumab)
At least 7 days from dinutuximab treatment
At least 8 weeks from prior cellular therapy or vaccine therapy with recovery of associated toxicities. If prior CAR T cells, need documented lack of persistence of prior product.
At least 6 weeks post 131I-MIBG therapy or other radioisotope therapy
At least 6 weeks post autologous stem cell therapy infusion following myeloablative conditioning
Participants can be eligible after autologous stem cell infusion without myelosuppressive therapy at any time as long as other criteria are met.
At least 12 weeks post allogeneic stem cell transplant with no evidence of GVHD or ongoing toxicities.
Steroid use: Corticosteroids at or below physiologic doses (replacement therapy for management of pituitary/adrenal insufficiency) is allowed and/or topical administration (e.g. inhaled or dermatologic) is allowed. Hydrocortisone for blood product premedication is allowed.
Participants must have normal marrow function as defined below: Values must be without transfusions or platelet growth factor within 7 days. Participants with known marrow involvement are exempt from these requirements.
hemoglobin ≥7.0g/dL
absolute neutrophil count ≥750/mcL
platelets ≥75,000/mcL
Adequate renal function defined as creatinine below normal limits for age OR creatinine clearance (as estimated by Cockcroft Gault Equation for participants ≥ 18yo and Bedside Schwartz for participants \<18yo) ≥70mL/min/1.73m2
Maximu Serum Creatinine (mg/dL)
6 months to 1 year: MALE = 0.5 FEMALE = 0.6
1 year \< 2 years: MALE = 0.6 FEMALE = 0.6
2 year \< 6 years: MALE = 0.8 FEMALE = 0.8
6 years \< 10 years: MALE = 1 FEMALE = 1
10 years \< 13 years: MALE = 1.2 FEMALE = 1.2
13 years \< 16 years: MALE = 1.5 FEMALE = 1.4
≥16 years: MALE = 1.7 FEMALE = 1.4
Adequate hepatic function
Serum ALT/AST \<3.0X ULN
Total bilirubin \< 3X ULN, except in participants with confirmed Gilbert's syndrome, where direct bilirubin must be \<3X ULN.
Adequate cardiac function
Ejection fraction ≥50% or fractional shortening ≥28%, measured by echocardiography
Adequate pulmonary function
No evidence of dyspnea at rest
No exercise intolerance due to pulmonary insufficiency
Pulse oximetry \>92% while breathing room air
Females of childbearing potential must have a negative serum or urine pregnancy test
The effects of B7-H3.CD28z.CART on the developing human fetus are unknown. For this reason and because other chemotherapeutic agents used in the study are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of the study, and for 1 year after receiving the preparative lymphodepletion regimen or for as long as B7-H3.CD28z.CARTs are detectable in peripheral blood. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, and for 1 year after receiving the preparative lymphodepletion regimen or for as long as B7-H3.CD28z.CARTs are detectable in peripheral blood.
Ability to understand and/or the willingness of their parent or legally authorized representative to sign a written informed consent document. Pediatric patients will be included in the consent discussion as age-appropriate and will provide written informed assent as applicable per institutional standard.
Exclusion
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.
Active or uncontrolled viral, bacterial or fungal infection. Participants may be receiving ongoing therapy for controlled infection.
Participants with a known additional malignancy other than non-melanomatous skin cancer or carcinoma in situ, unless not requiring active treatment and stable or disease-free for at least 3 years.
CNS disorder such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or autoimmune disease with CNS involvement that in the judgement of the investigator may impair the ability to evaluate neurotoxicity.
History of severe hypersensitivity reaction to compounds of similar chemical or biologic compositions to any agents used in the study or in the manufacturing of cells.
HIV/HBV/HCV infection: Participants are required to be negative for HIV Antibody or HIV viral load, negative for Hepatitis surface antigen (HbsAg) or viral load and negative for HCV antibody or HCV viral load. These participants are ineligible because of the potential for in vivo retroviral recombination events that could lead to replication-competent γ-retrovirus. A history of HIV, Hepatitis B, or Hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing.
Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Pregnant women are excluded from this study because the effects of B7-H3.CD28Z.CART cells on the developing fetus are unknown and because chemotherapeutic agents with the potential for teratogenic or abortifacient effects are used in this study. Because there is an unknown but potential risk for adverse events in nursing infants, secondary to treatment of the mother with B7-H3.CD28Z.CART cells and chemotherapy, breastfeeding should be discontinued if the mother is treated with T cells on this study (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
What this trial measures
- Manufacturing Success Rate of Autologous B7-H3.CD28Z CART CellsParticipants will receive the CART cell infusion on Day 0.
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.
- Maximum Tolerated Dose (MTD) of B7-H3.CD28Z.CART Cells28 days
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.