Safety of Labeled Dendritic Cell (DC) Vaccines and Feasibility of Tracking by Magnetic Resonance Imaging (MRI)

Pawel Kalinski

Status and phase: Completed; Phase 1

Conditions: Colorectal Carcinoma; Colorectal Tumors; Neoplasms, Colorectal; Colorectal Neoplasms; Colorectal Cancer

Treatments: Biological: DC Vaccine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01671592

R01CA134633 (U.S. NIH Grant/Contract)

10-052

Details and patient eligibility

About

This study will evaluate the safety and feasibility MRI tracking of a vaccine produced from a persons cancer cells injected intradermally once a day for 3 consecutive days. One of the daily doses will contain a chemical that can be detected by an MRI. That will be either the 1st or 3rd day of the 3 day course. On that day MRI scans will be performed 6 and 24 hours after the injection on that day. Patients may be able to receive booster doses every 1-2 months

Full description

STUDY EVALUATIONS

• Pre-Vaccination

  • Complete physical examination (with ECOG performance status (PS), medical history, weight, height, and BSA); the exact size and location of all tumor lesions will be noted in the flow sheet, documented in the text note, and by photographic and/or radiologic means
  • CEA levels in the blood (as a tumor marker)
  • Women of childbearing potential will have a serum beta-HCG pregnancy test
  • Anti-HIV, HbsAg and Anti-HCV
  • CBC, platelet, differential
  • Comprehensive metabolic panel (CMP) including: glucose, BUN, creatinine, sodium, potassium, Cl, CO2, calcium, total protein, albumin, alkaline phosphatase, AST, ALT, total bilirubin
  • PT/PTT testing
  • Electrocardiogram (EKG), if indicated
  • Radiologic imaging to evaluate the status of disease may be performed as a part of routine care.
  • Leukapheresis
  • Dendritic cell vaccine preparation

• Procedures during priming vaccination (Days 1 to 3)

  • Complete physical examination (with PS and weight)
  • 19F/1H MRI scanning on day of vaccination, 6 hrs (±1 hour) and 24 hrs (±4 hour) post-injection.
  • Blood for in vitro assays, before first i.d. administration on day 1 (baseline) and after the last i.d. administration on day 3
  • DTH tests: administration on day 1 and readout on day 3
  • Biopsy of the DTH site can be performed in any subject who consented to such biopsy, at the discretion of the investigator/sub-investigator (Day 3 only, based on readout)

• Procedures on Day 15

  • Complete physical examination (with ECOG PS and weight)
  • CBC, platelet, differential
  • Blood for in vitro assays

• Procedures during booster courses (Days 36 to 38, 64 to 66, and 91 to 93)

  • Complete physical examination (with PS and weight) on the 1st day of each 3 day course (Days 36, 64, and 91)
  • CBC, platelet, differential on the 1st day of each 3 day course (Days 36, 64, and 91)
  • Comprehensive metabolic panel (CMP) including: glucose, BUN, creatinine, sodium, potassium, Cl, CO2, calcium, total protein, albumin, alkaline phosphatase, AST, ALT, total bilirubin on the 1st day of each 3 day course (Days 36, 64, and 91)
  • DTH tests: administration on 1st day and readout on 3rd day during 2nd and 3rd booster courses (Administration days 64 and 91, readout days 66 and 93)
  • Biopsy of the DTH site can be performed in any subject who consented to such biopsy, at the discretion of the investigator/sub-investigator (3rd day of 3 day course, based on readout of DTH test)
  • Blood for in vitro assays (1st and 3rd day of each 3 day course)

• Procedures on Day 105

  • Complete physical examination (with ECOG PS and weight)
  • CEA levels in the blood (as a tumor marker)
  • CBC, platelet, differential
  • Comprehensive metabolic panel (CMP) including: glucose, BUN, creatinine, sodium, potassium, Cl, CO2, calcium, total protein, albumin, alkaline phosphatase, AST, ALT, total bilirubin
  • Radiologic imaging to evaluate the status of disease may be performed as a part of routine care
  • Photography

• Long term follow-up The subjects with lack of disease progression at 6 months after the last vaccination will be monitored for the disease free survival and overall survival. Subjects may be contacted every 3 months within the first three years after study intervention, every six months until year 5, and annually afterwards. In lieu of direct contact a medical record review may be performed to obtain the data for these time points for disease progression and/or survival.

Enrollment: 6 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Subjects must have adequate tumor tissue from surgery, performed as part of their conventional care.

• No chemotherapy, radiotherapy, major surgery, or biologic therapy for their malignancy in the 2 weeks prior to vaccine administration and they must have recovered from all side effects.

• An ECOG performance status of 0, 1, or 2.

• Age equal to 18 years or older.

• Blood tests:

  • Platelet counts greater than 80,000 (platelet count, hematocrit, and WBC will be re-evaluated within 2 weeks prior to leukapheresis)
  • Hematocrit > 27.0
  • White blood count > 2000/µL
  • Creatinine less than or equal to 2 X ULN

• Aware of the neoplastic nature of his/her illness, the experimental nature of the study intervention, alternative treatments, potential benefits and risks, and willing to sign a written informed consent document.

Exclusion criteria

• Subjects currently treated with systemic immunosuppressive agents, including steroids, are ineligible until 2 weeks after removal from immunosuppressive treatment. Subjects on maintenance steroids because of adrenal insufficiency are eligible.

• Subjects with total bilirubin greater than 2 X ULN.

• Subjects with uncontrolled pain.

• Subjects with active autoimmune disease, positive serology for HIV, HBV, or HCV. (Hypothyroidism is allowed.)

• Subjects who are allergic to or develop an allergy to heparin.

• Subjects who are pregnant.

• Subjects who have sensitivity to drugs that provide local anesthesia.

• Subjects who have medical contraindications for MRI. Such contraindications include:

  • Electrical implants such as cardiac pacemakers or perfusion pumps
  • Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye or steel implants
  • Ferromagnetic objects such as jewelry or metal clips in clothing
  • Pre-existing medical conditions, including claustrophobic reactions, the likelihood of developing a seizure or any greater than normal potential for cardiac arrest

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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6 participants in 4 patient groups

Day 1 MRI with low dose vaccine

Experimental group

Description:

DC vaccine at 3 x 10e6 per course which consists of 3 daily intradermal doses per course with the MRI on day 1 of the course.

Treatment:

Biological: DC Vaccine

Day 3 MRI with low dose vaccine

Experimental group

Description:

DC vaccine at 3 x 10e6 per course which consists of 3 daily intradermal doses per course with the MRI on day 3 of the course.

Treatment:

Biological: DC Vaccine

Day 1 MRI with high dose vaccine

Experimental group

Description:

DC vaccine at 3 x 10e7 per course which consists of 3 daily intradermal doses per course with the MRI on day 1 of the course.

Treatment:

Biological: DC Vaccine

Day 3 MRI with high dose vaccine

Experimental group

Description:

DC vaccine at 3 x 10e7 per course which consists of 3 daily intradermal doses per course with the MRI on day 3 of the course.

Treatment:

Biological: DC Vaccine