Dendritic Cell Vaccine for Children and Adults With Sarcoma
关键词
抽象
描述
This is a dose finding / dose escalation study of dendritic cell (DC) vaccination administered through imiquimod (Aldara®) treated skin for refractory sarcoma patients, which includes a subsequent cohort of subjects who will receive DC and gemcitabine (Gemzar®) therapy. There are three intended dose levels for cell number of DC per treatment - 3, 6 and 12 million cells per treatment. There will be 5 subjects accrued per dose level. If one subject in the first 5 patients per dose level experiences a dose limiting toxicity (DLT), then the dose level will be expanded to 8 subjects. If 2 or more of the subjects at a given dose level experience a DLT, then the maximum tolerated dose (MTD) will be considered to have been exceeded. The MTD will be the cell dose level at which less than 1 in 5 or less than 2 in 8 subjects experience a DLT. Provision will be made to de-escalate to dose level 0, or 1.5 million cells per treatment, should dose level 1 be too toxic. This is a 5+3 design modified from the conventional 3+3 dose escalation schema used for testing cytotoxic agents in Phase I trials. A lower rate of DLTs is therefore potentially to be accepted on this study than on such a conventional dose escalation trial of a cytotoxic agent. If no MTD is reached, we will consider the third dose level to be the recommended phase 2 dose (RP2D) going forward and expand this dose level to 8 subjects in total.
After the MTD/RP2D is reached, we will commence with the addition of gemcitabine pre-treatment to the study therapy with the cell dose held at the dose determined for the DC alone. This will include weekly gemcitabine infusion for three weeks out of four before the initiation of vaccination. Gemcitabine treatment will commence as soon as the subject has safely recovered from pheresis, but within 2 weeks of completion of pheresis. DC vaccination will begin two weeks after the third administration of gemcitabine. Gemcitabine dosing will be constant, but should the combination of gemcitabine with the MTD/RP2D of DC alone prove too toxic, we will de-escalate the dose of DC on the gemcitabine containing levels. This de-escalation will mirror the dose escalation for DC alone, and the MTD for the DC plus gemcitabine will be defined as the dose level at which less than 1 in 5 or less than 2 in 8 subjects experience a DLT.
Subjects will undergo resection of tumor followed by pheresis to acquire monocytes which will be separated and used to grow out DC. Subjects not undergoing gemcitabine therapy will begin vaccination approximately two weeks after pheresis, depending on the manufacture time of their DC. All subjects will undergo lysate boost administration.
日期
最后验证: | 05/31/2020 |
首次提交: | 02/26/2013 |
提交的预估入学人数: | 02/27/2013 |
首次发布: | 03/03/2013 |
上次提交的更新: | 06/23/2020 |
最近更新发布: | 06/24/2020 |
实际学习开始日期: | 01/05/2014 |
预计主要完成日期: | 09/09/2019 |
预计完成日期: | 07/22/2024 |
状况或疾病
干预/治疗
Biological: Dendritic Cells Vaccine
Biological: Lysate of Tumor
Drug: Part 2-Gemcitabine/DC Vaccine/Lysate
Drug: Imiquimod
Procedure: Leukapheresis
相
手臂组
臂 | 干预/治疗 |
---|---|
Experimental: Part 1-DC Vaccine/Lysate Leukapheresis: Baseline, post-surgery;
Dendritic Cells Vaccine (DC Vaccine): Post-Leukapheresis, administered once weekly in dose-escalation scheme for 4 weeks;
Lysate of Tumor (Lysate): Post-DC Vaccine therapy, administered during weeks 8, 12, 16 and 20;
Imiquimod: Self-applied topically by subject before and after scheduled DC Vaccine or Lysate administrations. | |
Active Comparator: Part 2-Gemcitabine/DC Vaccine/Lysate Leukapheresis: Baseline, post-surgery;
Gemcitabine: Post-Leukapheresis, administered once weekly for 3 weeks;
Dendritic Cells Vaccine (DC Vaccine): Post-Gemcitabine therapy, Recommended Phase 2 Dose (RP2D) administered once weekly for 4 weeks;
Lysate of Tumor (Lysate): Post-DC Vaccine therapy, administered during weeks 12, 16, 20 and 32;
Imiquimod: Self-applied topically by subject before and after scheduled DC Vaccine or Lysate administrations. | Drug: Part 2-Gemcitabine/DC Vaccine/Lysate Post-surgery, Leukapheresis and clearance of subject. Gemcitabine 1000 mg/m2 IV will be administered once weekly for 3 weeks per study protocol. |
资格标准
有资格学习的年龄 | 1 Year 至 1 Year |
有资格学习的性别 | All |
接受健康志愿者 | 是 |
标准 | Inclusion Criteria: 1. Age: 1 - 100 years old. 2. Histologically or cytologically confirmed sarcoma either relapsed or without known curative therapies. Both bone sarcomas and soft tissue sarcomas are eligible. Osteosarcoma, chondrosarcoma, Ewing's sarcoma and any other diagnoses of sarcoma are eligible as long as there is soft tissue that can be excised and be used to prepare lysate. Subjects presenting only with lesions that are only comprised of bone are excluded. Any number of prior therapies is allowed, including zero. 3. No radiotherapy to other sites planned and/or other chemotherapy planned for the study period. No radiotherapy or chemotherapy to have been received for at least 4 weeks before first vaccine administration. To allow for better local control without introducing undue toxicity into the trial, brachytherapy at time of surgery scheduled to end by one week before first vaccination is allowed if the radioactive source is to be removed (e.g. catheters can be placed if removable but implanted seeds are not allowed). In the event of positive margins being determined after surgical resection, but not determined in time for the placement of brachytherapy catheters, external beam radiotherapy may start after the last DC vaccination is administered but before the lysate boosts begin, and radiation must be planned to be complete before the first lysate boost. 4. No treatment with corticosteroids, antihistamines or salicylates for at least 1 week before first vaccination. 5. Adequate organ function (to be measured at enrollment) - Absolute neutrophil count (ANC) ≥ 0.75* 10^3/µL - Lymphocytes ≥ 0.5 * 10^3/µL - Platelets ≥ 75 * 10^3/µL - Hemoglobin ≥ 9 g/dL - Aspartate aminotransferase (AST)/Alanine transaminase (ALT) ≤ 2.5 X upper limit of normal (ULN); if liver metastases, ≤ 5 X ULN - Serum Creatinine ≤ 1.5 X ULN - Total Bilirubin ≤ 3 X ULN - Albumin > 2 g/dL 6. Karnofsky/Lansky score of ≥ 70% or Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 7. Subjects must agree to use adequate method of contraception or abstinence throughout and up to 4 weeks after the study treatment completion. 8. Life expectancy of > 3 months. 9. Written consent by patient or parent(s) (if patient is < 18 years) on an institutional review board (IRB)-approved informed consent form prior to any study-specific evaluation. Assent is required from children as per University of Miami (UM) IRB guidelines. Subject must be capable of understanding the investigational nature, potential risks and benefits of the study and able to provide valid informed consent. Exclusion Criteria: 1. Pregnancy 2. Breast feeding females. 3. Any concomitant participation in other therapeutic trials 4. Virus serology known to be positive for HIV (testing is not required in the absence of clinical suspicion) 5. Documented immunodeficiency or autoimmune disease 6. Concomitant treatment with corticosteroids, antihistamines (H1 and H2 inhibitors) or salicylates. Patients may be eligible if the treatment is stopped at least 1 week before the first vaccination. 7. Brain metastases unless they have been stable for 3 months off of treatment directed specifically at them. 8. Known allergy to gemcitabine or its formulation components. Intolerant to gemcitabine - Does not apply to cohorts to be treated without gemcitabine - Prior therapy with gemcitabine is allowed on all cohorts 9. Refusal to use adequate contraception for fertile patients (females and males) during the study and for 30 days after the last dose of study treatment. 10. Any serious or uncontrolled medical or psychiatric condition that in the opinion of the investigator makes the patient not able to participate in the study. |
结果
主要结果指标
1. Number of Participants with Adverse Events as a Measure of Safety and Tolerability [From Day 1 to 30 Days Post-Treatment, about 9 months]
次要成果指标
1. Measurement levels of Myeloid Derived Supressor Cells before and after treatment [From Baseline to 3 Months Post-Treatment, up to 12 months]
2. Progression-free survival [Up to 24 months Post-Treatment]
3. Overall Survival [Up to 5 years Post-Treatment]
4. The rate of Complete Response (CR) or Partial Response (PR) in subjects receiving treatment [Up to 24 months Post-Treatment]
5. Measurement levels of Myeloid Derived Supressor Cells after Gemcitabine treatment [From Baseline to End of Treatment, about 10 months]