GAPVAC Phase I Trial in Newly Diagnosed Glioblastoma Patients

• Status: Completed
• Trial end date: 2018-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of this study is to assess the safety and tolerability, feasibility and biological activity (immunogenicity) of the actively personalized vaccination (APVAC) concept in newly diagnosed glioblastoma (GB) patients.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: immatics Biotechnologies GmbH
• Collaborators: BCN Peptides; Biontech AG; BioNTech SE; EU-funded GAPVAC Consortium; University Hospital Tuebingen
• Treatments: Adjuvants, Immunologic; Carboxymethylcellulose Sodium; Immunologic Factors; Molgramostim; Poly I-C; Poly ICLC; Sargramostim; Temozolomide; Vaccines

Criteria

Inclusion Criteria:

1. Histologically confirmed, newly diagnosed GB (astrocytoma WHO grade IV)

2. HLA phenotype defined by warehouse composition (HLA-A*02:01 or HLA-A*24:02 positive patients only; both as determined by a PCR-based 4-digit typing method)

3. Gross total resection (as defined by less than 1 cm2 residual tumor mass on the largest perpendicular axes in post-operative scan taken within 48 h post-surgery; standard MRI conformable to the present national and international guidelines is sufficient)

4. At least 0.5 g tumor tissue freshly cryopreserved during surgery

5. Age ≥18 years

6. KPS ≥70%

7. Life expectancy > 6 months

8. Patient is a candidate for and willing to receive standard CRT with TMZ followed by maintenance TMZ cycles

9. Patient is not on steroids or on stable or decreasing steroid levels not exceeding 2 mg/day dexamethasone (or equivalent doses of other steroids) during the last 3 days prior to enrollment

10. Absolute lymphocyte count (ALC) >1.0 x109/L (re-screening of lymphocyte counts is allowed)

11. Ability of subject to understand and the willingness to sign written informed consent for study participation. Written consent by a legally authorized representative is not sufficient.

12. Availability of an APVAC analysis and manufacturing slot confirmed by the sponsor

13. Female patients who are post-menopausal (no menstrual period for a minimum of 1 year), or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), practice one of the following medically acceptable methods of birth control (hormonal methods, intrauterine device or double-barrier methods) or practice total abstinence

14. Male patients willing to use contraception (condoms with spermicidal jellies or cream) upon study entry and during the course of the study, have undergone vasectomy or are practicing total abstinence

Exclusion Criteria:

1. Abnormal (≥ Grade 2 CTCAE v4.0) laboratory values for hematology, liver and renal function (serum creatinine). In detail the following values apply as exclusion criteria:

1. Hemoglobin < 10 g/dL (6.2 mmol/L)

2. White blood cell count (WBC) decrease (<3.0 x109/L) or increase (>10.0 x109/L)

3. Absolute neutrophil count (ANC) decrease < 1.5 x109/L

4. Platelet count decrease < 75 x109/L

5. Bilirubin > 1.5 x ULN (upper limit of normal according to the performing lab's reference range)

6. ALAT > 3 x ULN

7. ASAT > 3 x ULN

8. GGT6 > 2.5 x ULN

9. Serum creatinine increased > 1.5 x ULN

2. HIV infection or active Hepatitis B or C infection, or active infections requiring oral or intravenous antibiotics or that can cause a severe disease and pose a severe danger to lab personnel working on patients' blood or tissue (e.g. rabies).

3. Prior therapy for glioma (except surgery and steroids) including but not limited to carmustine wafers and immunotherapy

4. Any condition contraindicating leukapheresis from peripheral veins

5. Concurrent participation in another interventional clinical trial studying a drug or treatment regimen.

6. Clinically relevant autoimmune diseases (with the exception of thyroid diseases)

7. Immunosuppression, not related to prior treatment for malignancy, or prior drug reaction

8. Any condition that in the judgment of the investigator interferes with the probability that an individual patient may receive and benefit from APVAC vaccinations (e.g. high risk of early disease progression / recurrence; immunocompromised status; anticipated compliance problems)

9. Serious illness or condition, which according to the investigator, poses an undue risk for the patient when participating in the trial, including, but not limited to, any of the following:

• Clinically significant cardiovascular disease

• New York Heart Association class III-IV congestive heart failure

• Symptomatic peripheral vascular disease

• Severe pulmonary dysfunction

• Severe diabetes

• Severe mental retardation

10. History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within the last 5 years unless the patient has been disease-free for 5 years

11. Pregnancy or breastfeeding