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Protocol Details

GD2-CAR PERSIST: Production and Engineering of GD2-Targeted, Receptor Modified T Cells (GD2CART) for Osteosarcoma or Neuroblastoma to Increase Systemic Tumor Exposure

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 4 wk
Max Age: 40 Years

Referral Letter Required


Population Exclusion(s)

Pregnant Women


Immunologic Factors;
Adoptive Immunotherapy;
Dose Escalation

Recruitment Keyword(s)



Neuroectodermal Tumors;

Investigational Drug(s)

AP1903 (rimiducid)

Investigational Device(s)



Drug: Fludarabine Phosphate
Drug: Cyclophosphamide
Biological/Vaccine: GD2-CAR-expressing Autologous T-lymphocytes

Supporting Site

National Cancer Institute


A new cancer treatment involves taking a person s own immune cells (called T cells), genetically modifying them to help the T cells kill cancer cells, and then giving them back to the person. Researchers want to see if this treatment can help people with neuroblastoma or osteosarcoma.


To see if an immune cell therapy called GD2CART is safe and able to shrink neuroblastoma or osteosarcoma.


People aged 40 years and younger with neuroblastoma or osteosarcoma that has come back or has not responded to standard treatments.


Participants will be screened with a medical record review.

Participants will have blood tests and heart function tests. They will have body imaging scans, x-rays, or bone scans. They may have bone marrow aspirations. They may have tissue biopsies. Some samples will be used for genetic tests.

Participants will undergo apheresis to collect T cells. It will take 2 3 weeks to make the modified cells (called GD2CART).

Participants will receive 2 chemotherapy drugs, fludarabine and cyclophosphamide, over 4 days by intravenous (IV) infusion through a vein in the arm or through a central line. Then they will get GD2CART by IV infusion. They will be monitored closely a few times a week for 4 weeks after the infusion.

Participants will have follow-up visits once a month for 6 months, then every 3 months until the end of the second year. Then they will be contacted once a year for up to 15 years. They may be able to receive a second dose of GD2CART if needed.

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--Must have histologically confirmed neuroblastoma or osteosarcoma that is recurrent or refractory and for which standard curative measures do not exist or are no longer effective. Must have histologic verification of their disease at diagnosis or at relapse.

-Disease Status

--Patients with osteosarcoma must have progressive, recurrent or refractory disease after all curative measures, including first line chemotherapy.

--Patients with osteosarcoma in the dose escalation cohort, must have evaluable or measurable disease at enrollment.

--Patients with osteosarcoma in the expansion cohort must have measurable disease by RECIST v1.1 at enrollment.

--Patients with neuroblastoma in the dose escalation or dose the expansion cohort must have:

---Prior progressive disease OR refractory disease present since diagnosis

---AND at least one of the following:

----Any amount of tumor in BM

----At least one MIBG-avid soft tissue or skeletal site

----For MIBG-nonavid disease, at least one FDG-PET- positive soft tissue or skeletal site plus past histologic confirmation

---Progressive disease is defined as any disease progression occurring at any time after the diagnosis of high-risk neuroblastoma. Refractory disease is defined as an incomplete response of high-risk neuroblastoma to all treatments but without disease progression

-Age: Must be <40 years of age.

-Prior Therapy

--There is no limit to the number of prior treatment regimens. The following washout periods prior to leukapheresis apply to patients undergoing leukapheresis on this study. If a patient has cryopreserved PBMCs stored, the following washout periods are strongly recommended but not required and the product is useable if it meets the criteria established in this IND.

--Myelosuppressive chemotherapy: Patients must not have received myelosuppressive chemotherapy within 3 weeks of leukapheresis (6 weeks if prior nitrosourea).

--Hematopoietic growth factors: At least 7 days must have elapsed since the completion of therapy with a growth factor. At least 14 days must have elapsed after receiving pegfilgrastim.

--Biological agent, tyrosine kinase inhibitor, targeted agent, metronomic chemotherapy: At least 7 days must have elapsed since the completion of therapy with a biologic agent, tyrosine kinase inhibitor, targeted agent, or metronomic non-myelosuppressive regimen.

--131I-MIBG or other radioisotope therapy: At least 6 weeks must have elapsed since prior therapy with 131I-MIBG. At least 6 weeks or 10 half-lives (whichever is shorter) must have elapsed since prior therapy with any other radioisotope.

--Monoclonal antibodies and checkpoint inhibitors: At least 3 weeks or 5 half-lives (whichever is shorter) must have elapsed since prior therapy that included a monoclonal antibody or checkpoint inhibitor.

--Radiotherapy (XRT): 3 weeks must have elapsed since XRT, but at least 6 weeks if CNS or lung fields, with the exception that there is no time restriction for palliative radiation with minimal bone marrow involvement and the patient has measurable/evaluable disease outside the radiation port or the site of radiation has documented progression.

--Vaccine therapy, anti-GD2 mAb therapy, or therapy with any genetically engineered T cells: Patients may have received previous vaccine therapy, anti-GD2 mAb therapy, or therapy with any genetically engineered T cells except prior GD2 CAR T cell therapy. At least 3 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior vaccine or monoclonal antibody therapy. At least 42 days must have elapsed since prior modified T cell, NK cell, or dendritic cell therapy.

--Allogeneic stem cell transplant/infusion: At least 12 weeks must have elapsed since allogeneic stem cell transplant and without evidence of active graft versus host disease (GVHD). Patients who received an autologous stem cell infusion following myeloablative therapy should be at least 6 weeks from their infusion. Patients who received an autologous stem cell infusion following non-myeloablative therapy do not have a wash-out period; they are eligible once they meet all other eligibility requirements, including recovery from acute side effects. This criterion does not apply to patients with apheresis product or usable T cell product available for use.

-Apheresis Parameters

--Must meet parameters for apheresis per institutional guidelines. (This criterion does not apply to patients with apheresis product or usable T cell product available for use. Cryopreserved PBMCs stored from participation in other institutional cell therapy or cell collection studies or standard of care may be used to generate the cellular product on this study if they meet the criteria established in this IND.

-Performance Status

--Patients > 16 years of age must have Karnofsky >= 50%. Patients <= 16 years of age must have Lansky scale >= 50%; or ECOG performance status <= 2.

-Organ and Marrow Function

--Must have organ and marrow function as defined below (supportive care is allowed per institutional standards, i.e., filgrastim, transfusion):

Organ and Marrow Function Requirements:

-- Organ: Bone Marrow Function

--- Laboratory Element: Leukocytes; Minimum Requirement: >= 750/mcL*

--- Laboratory Element: Platelets; Minimum Requirement: >= 75,000/mcL*

-- Organ: Liver Function; Laboratory Element: AST(SGOT)/ALT(SGPT) (For the purpose of this study, the ULN for SGOT is 50 U/L and the ULN for SGPT is 45 U/L); Minimum Requirement: <= 5 x ULN

-- Organ: Liver Function; Laboratory Element: Total bilirubin; Minimum Requirement: <= 2 x institutional upper limit of normal (ULN) for age (Patients with Gilbert s syndrome are excluded from the requirement of a normal bilirubin and patients will not be excluded if bilirubin elevation is due to tumor involvement. [Gilbert s syndrome is found in 3-10% of the general population, and is characterized by mild, chronic unconjugated hyperbilirubinemia in the absence of liver disease or overt hemolysis]. Note: Adult values will be used for calculating hepatic toxicity and determining eligibility.

-- Organ: Renal Function

--- Age: 1 month to < 6 months; Minimum Requirement: Maximum serum creatinine (mg/dL), Male 0.4, Female 0.4

--- Age: 6 months to < 1 year; Minimum Requirement: Maximum serum creatinine (mg/dL), Male 0.5, Female 0.5

--- Age: 1 to < 2 years; Minimum Requirement: Maximum serum creatinine (mg/dL), Male 0.6, Female 0.6

--- Age: 2 to < 6 years; Minimum Requirement: Maximum serum creatinine (mg/dL), Male 0.8, Female 0.8

--- Age: 6 to < 10 years; Minimum Requirement: Maximum serum creatinine (mg/dL), Male 1, Female 1

--- Age: 10 to < 13 years; Minimum Requirement: Maximum serum creatinine (mg/dL), Male 1.2, Female 1.2

--- Age: 13 to < 16 years; Minimum Requirement: Maximum serum creatinine (mg/dL), Male 1.5, Female 1.2

--- Age: >= 16 years; Minimum Requirement: Maximum serum creatinine (mg/dL), Male 1.7, Female 1.4 OR

--- Creatinine clearance or glomerular filtration rate (GFR); >= 60 mL/min/1.73 m^2 for patients with levels above institutional normal.

-- Organ: Cardiac Function; Minimum Requirement: Cardiac ejection fraction >= 45% or shortening fraction >= 28%, no evidence of physiologically significant pericardial effusion as determined by an ECHO. No clinically significant ECG findings.

-- Organ: Pulmonary Function; Laboratory Element: Pulmonary status; Minimum Requirement: No clinically significant pleural effusion. Baseline oxygen saturation > 92% on room air at rest.

-- Organ: Neurological Function; Laboratory Element: Neurologic status; Minimum Requirement: Baseline neurotoxicity equal to grade 1 or less.

*Cytopenias deemed to be disease-related and not therapy-related are exempt from this exclusion. Patients must not be refractory to transfusions.


--Females of child-bearing potential and males of reproductive potential who are sexually active must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 4 months after completion of chemotherapy preparative administration or until CAR is no longer detectable, whichever is later. Should a female become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

Note: Females of childbearing potential are defined as those who are past the onset of menarche and are not surgically sterile (i.e., bilateral salpingectomy, bilateral oophorectomy, complete hysterectomy) or post-menopausal.

-Informed Consent: All patients >= 18 years of age must be able to give informed consent or if unable to give consent have a legal authorized representative (LAR) who can give consent for the patient. For patients < 18 years old their LAR (i.e., parent or legal guardian) must give informed consent. Pediatric patients will be included in age appropriate discussion and verbal assent will be obtained for those > 7 years of age, when appropriate, according to local policy.


-Receiving any other current investigational agents.

-History of anaphylactic reactions attributed to anti-GD2 antibodies or to compounds of similar chemical or biologic composition to GD2CART, cyclophosphamide, fludarabine, or other agents used in this study. History of hypersensitivity to dornase alfa, Chinese Hamster Ovary cell products, or any of the components of Pulmozyme.

-Patients who require systemic corticosteroid or other immunosuppressive therapy. (A one- week washout from systemic corticosteroid or other immunosuppressive therapy is permitted.) Use of physiologic doses of corticosteroids (up to 3 mg/m2/day prednisone equivalent) are permitted. Use of topical, ocular, intra-articular, intra-nasal, or inhaled corticosteroids are permitted.

-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.

-History of additional malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, breast) unless untreated and stable or disease free for at least 3 years.

-Untreated central nervous system (CNS) metastasis. Patients with previous CNS tumor involvement that has been treated and is stable for at least 6 weeks following completion of therapy are permitted. Patients who are clinically stable as evidenced by no requirements for corticosteroids, no evolving neurologic deficits, and no progression of residual brain abnormalities without specific therapy, are permitted. Patients with asymptomatic subcentemeric CNS lesions are permitted if no immediate radiation or surgery is indicated.

-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.

-Presence of fungal, bacterial, viral, or other infection that is uncontrolled.

-Ongoing infection with HIV, hepatitis B (HBsAg positive), or hepatitis C virus (anti-HCV positive) as the immunosuppression contained in this study will pose unacceptable risk. 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.

-Primary immunodeficiency or history of systemic autoimmune disease (e.g., Crohns, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years.

-Females of childbearing potential must have a negative serum or urine pregnancy test. Pregnant females are excluded from this study because the effects of autologous GD2CART on the developing human fetus are unknown and because the chemotherapy agents used in this trial (cyclophosphamide and fludarabine) are category D agents with the potential for teratogenic or abortifacient effects. Additionally, because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with cyclophosphamide/fludarabine, breastfeeding should be discontinued if the mother is treated with cyclophosphamide/fludarabine. These potential risks may also apply to other agents used in this study.

-Patients with known GD2 negative tumors by validated IHC will be excluded from enrollment given the change in risk profile.

-In the investigator s judgment, unlikely to complete protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation. Or in the investigator's judgment, if the patient is likely to develop significant toxicity and morbidity from CAR-T cell expansion mediated inflammation based on location of tumor site.

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Not Provided

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Principal Investigator

Referral Contact

For more information:

Rosandra N. Kaplan, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CRC BG RM 1-3940
(240) 760-6198

Elaine W. Thomas
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 1C244
10 Center Drive
Bethesda, Maryland 20892
(240) 858-7013

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office

Clinical Trials Number:


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