Pembrolizumab and a Vaccine (ATL-DC) for the Treatment of Surgically Accessible Recurrent Glioblastoma

  • STATUS
    Recruiting
  • End date
    Aug 1, 2025
  • participants needed
    40
  • sponsor
    Jonsson Comprehensive Cancer Center
Updated on 19 April 2022
cancer
monoclonal antibodies
metastatic disease
nitrosoureas
direct bilirubin
karnofsky performance status
international normalized ratio
neutrophil count
tumor cells
pembrolizumab
vaccine therapy
aptt
glioblastoma multiforme
malignant glioma
tumor progression
low grade glioma
formalin-fixed paraffin-embedded
surgical diagnosis

Summary

This phase I trial studies the side effects and how well of pembrolizumab and a vaccine therapy (ATL-DC vaccine) work in treating patients with glioblastoma that has come back (recurrent) and can be removed by surgery (surgically accessible). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Vaccines, such as ATL-DC vaccine, may help the body build an effective immune response to kill tumor cells. Giving pembrolizumab and ATL-DC vaccine may work better in treating patients with glioblastoma compared to ATL-DC alone.

Description

PRIMARY OBJECTIVES:

I. To evaluate the influence of pembrolizumab on the cell cycle-related genetic signature within the tumor microenvironment of progressive/recurrent glioblastoma.

II. To evaluate the influence of adjuvant autologous tumor lysatepulsed dendritic cell (ATL-DC) vaccination on peripheral T cell responses.

III. To evaluate the safety and tolerability of pembrolizumab and ATL-DC vaccination in progressive/recurrent glioblastoma.

SECONDARY OBJECTIVES:

I. To estimate the 6 month progression-free survival (PFS6) based on Response Assessment in Neuro-Oncology (RANO) criteria in patients treated on both arms of the clinical trial.

II. To calculate the overall survival of recurrent glioblastoma patients treated on both arms of the clinical trial.

EXPLORATORY OBJECTIVES:

I. To evaluate the associations between exploratory biomarkers, clinical outcomes, and adverse events which include:

Ia. Estimating the correlation of quantitative assessments of tumor infiltrating lymphocyte (TIL) density or the interferon (IFN) gamma-associated genetic signature with clinical responses to pembrolizumab and ATL-DC in recurrent glioblastoma patients.

Ib. Estimating the efficacy of pembrolizumab and ATL-DC through PFS6, PFS and overall survival (OS) as defined by RANO.

Ic. Estimating the efficacy of pembrolizumab and ATL-DC through PFS6, PFS, and OS as defined by immunotherapy RANO (iRANO).

Id. Exploring whether oligoclonal T cell populations within tumor tissue are similarly expanded in peripheral blood after ATL-DC vaccination and/or pembrolizumab, and correlating with clinical responses.

Ie. Exploring whether changes in specific magnetic resonance imaging (MRI) parameters correlate with tumor and peripheral blood immune responses.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP A: Beginning 14 days prior to scheduled surgery, patients receive pembrolizumab intravenously (IV) over 30 minutes. After surgery, patients receive pembrolizumab IV over 30 minutes on day 1. Cycle repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive ATL-DC intradermally (ID) with poly ICLC intramuscularly (IM) every 2 weeks for up to 3 doses in the absence of disease progression or unacceptable toxicity.

GROUP B: Beginning 14 days prior to scheduled surgery, patients receive placebo IV. After surgery, patients receive placebo IV on day 1. Cycle repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive ATL-DC ID with poly ICLC IM every 2 weeks for up to 3 doses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.

Details
Condition Recurrent Glioblastoma
Treatment Pembrolizumab, Placebo Administration, Poly ICLC, Dendritic Cell Tumor Cell Lysate Vaccine
Clinical Study IdentifierNCT04201873
SponsorJonsson Comprehensive Cancer Center
Last Modified on19 April 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Participants with histologically confirmed diagnosis of surgically accessible recurrent/progressive glioblastoma will be enrolled in this study
Be at first or second relapse (Note: relapse is defined as progression following initial therapy, i.e., radiation +/- chemotherapy. For participants who had prior therapy for a low-grade glioma, the surgical diagnosis of a high-grade glioma will be considered the first relapse)
Must be undergoing surgery that is clinically indicated, and eligible for resection with the expectation that the surgeon is able to resect at least 2 gram of tumor for lysate and research with low risk of inducing neurological injury
A male participant must agree to use a contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period
A female participant who has childbearing potential must have negative urine or serum pregnancy test 72 hrs prior to the first dose and be willing to use adequate method of contraception for course of study and 120 days after last dose
The participant (or legally acceptable representative if applicable) provides written informed consent for the trial
Have unequivocal evidence for contrast enhancing tumor progression by RANO criteria based on MRI scan within 14 days prior to randomization
Have a minimum tumor size of 2 x 2 cm^2 based on MRI scan prior to surgery
An interval of the following durations prior to randomization
At least 28 days from prior surgical resection
At least 7 days from prior stereotactic biopsy
At least 12 weeks from prior radiotherapy, unless there is unequivocal histologic confirmation of tumor progression
At least 23 days from prior chemotherapy
At least 42 days from nitrosureas
Have sufficient archival tumor tissue confirming glioblastoma or variants for
submission following registration. The following amount of tissue is required
Have a Karnofsky performance status (KPS) >= 70
Absolute neutrophil count (ANC) >= 1500/uL (uL=microliter) (collected within 14 days prior to the start of study treatment)
formalin-fixed, paraffin embedded (FFPE) tissue block (preferred) or 10 FFPE
Platelets >= 100 000/uL (collected within 14 days prior to the start of study treatment)
unstained slides (5um thick)
Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L (collected within 14 days prior to the start of study treatment)
Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks
Creatinine clearance (CrCl) should be calculated per institutional standard
Creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT[) =< 2.5 x ULN (=< 5 x ULN for participants with liver metastases) (collected within 14 days prior to the start of study treatment)
International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants (collected within 14 days prior to the start of study treatment)
clearance >= 30 mL/min for participant with creatinine levels > 1.5 x
aPTT =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants (collected within 14 days prior to the start of study treatment)
institutional ULN (collected within 14 days prior to the start of study
treatment) (glomerular filtration rate [GFR] can also be used in place of
creatinine or creatinine clearance [CrCl])
Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total
bilirubin levels > 1.5 x ULN (collected within 14 days prior to the start of
study treatment)

Exclusion Criteria

A woman of childbearing potential (WOCBP) who has a positive urine pregnancy test within 72 hours prior to randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137)
Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to randomization
Note: Participants must have recovered from all adverse events (AEs) due to previous therapies to =< grade 1 or baseline. Participants with =< grade 2 neuropathy may be eligible
Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment
Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus calmette-guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist) are live attenuated vaccines and are not allowed
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
Has known tumor primarily localized to the brainstem or spinal cord
Has severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients
Has received prior radiotherapy within 2 weeks of start of study treatment
Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
Participants must have recovered from all radiation-related toxicities, not
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
require corticosteroids, and not have had radiation pneumonitis. A 1-week
Has an active infection requiring systemic therapy
washout is permitted for palliative radiation (=< 2 weeks of radiotherapy) to
Has a known history of human immunodeficiency virus (HIV)
non-central nervous system (CNS) disease
Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as hepatitis C virus [HCV] ribonucleic acid [RNA] is detected) infection. Note: no testing for hepatitis B and hepatitis C is required unless mandated by local health authority
Has a known history of active TB (Bacillus tuberculosis)
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form
of immunosuppressive therapy within 7 days prior to the first dose of study
drug
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