Autologous CMV-Specific Cytotoxic T Cells and Temozolomide in Treating Patients With Glioblastoma

NCT02661282 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2014-0899NCI-2016-00183
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and best dose of autologous cytomegalovirus (CMV)-specific cytotoxic T cells when given together with temozolomide and to see how well they work in treating patients with glioblastoma. Autologous CMV-specific cytotoxic T cells may stimulate the immune system to attack specific tumor cells and stop them from growing or kill them. Drugs used in chemotherapy, such as temozolomide, may work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving autologous CMV-specific cytotoxic T cells with temozolomide may be a better treatment for patients with glioblastoma.

Conditions

Cytomegalovirus Positive; Glioblastoma; Gliosarcoma; Malignant Glioma; Recurrent Brain Neoplasm; Recurrent Glioblastoma

Outcome Measures

Primary Outcomes (4)

• Maximum Tolerated Dose (MTD) (Recurrent Glioblastoma Participant Cohort)- Phase I

  The number of participants who were treated at the respective dose level without DLT

  Up to 42 days

• Number of Participants With Immunological Effects in Tumor Tissue (Recurrent Glioblastoma Cohort)- Phase II

  Descriptive statistics will be used to summarize immunological effect. To evaluate the tumor-mediated immune suppression at the effector location, the markers (interferon, interleukin-2, and tumor necrosis factor alpha, perforin, granzyme B) will be measured for immune responses in the tumor microenvironment rather than in the peripheral blood.

  Up to 4 years

• Progression Free Survival (PFS) (Recurrent Glioblastoma Cohort) at 6 Months- Phase II

  Progression-free survival (PFS) is defined as the time from study enrollment until the time of first disease progression, relapse, or death due to disease. Patients who are alive without progression or relapse will be censored at the time of last contact. The point estimate of 6-month progression-free survival (PFS6) will be analyzed. Kaplan-Meier curves will be generated and median survival time will be derived.

  6 months

• Overall Survival (OS) (Newly Diagnosed Glioblastoma Cohort)- Phase II

  Overall Survival is defined as the time from definitive histological diagnosis until the time of death.

  Time from definitive histological diagnosis until death

Secondary Outcomes (4)

• Time to Progression (Recurrent Glioblastoma Cohort)- Phase II

  Baseline to disease progression, assessed up to 4 years

• Overall Objective Response Rate (ORR) (Newly Diagnosed Glioblastoma Cohort)- Phase II

  Up to 4 years

• Median Duration of Response (Newly Diagnosed Glioblastoma Cohort)- Phase II

  Baseline to response, assessed up to 4 years

• Progression Free Survival (PFS) (Newly Diagnosed Glioblastoma Cohort)- Phase II

  At 6 months

Study Arms (2)

Arm I (temozolomide, CMV-specific T cells, surgery)

EXPERIMENTAL

Patients receive temozolomide PO QD on days 1-21 and CMV-specific T cell transfer IV over 1-5 minutes on day 22. Patients undergo surgery on day 30 of cycle 1. Treatment repeats every 42 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive temozolomide PO QD on days 1-21. Treatment repeats every 42 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Biological: Autologous Cytomegalovirus-specific Cytotoxic T-lymphocytes; Other: Laboratory Biomarker Analysis; Drug: Temozolomide; Procedure: Therapeutic Conventional Surgery

Arm II (temozolomide, CMV-specific T cells)

ACTIVE COMPARATOR

Patients receive temozolomide PO QD on days 1-21 and CMV-specific T cell transfer intravenously IV over 1-5 minutes on day 22. Treatment repeats every 42 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Biological: Autologous Cytomegalovirus-specific Cytotoxic T-lymphocytes; Other: Laboratory Biomarker Analysis; Drug: Temozolomide; Procedure: Therapeutic Conventional Surgery

Interventions

Autologous Cytomegalovirus-specific Cytotoxic T-lymphocytes BIOLOGICAL

Given IV

Also known as: Autologous CMV-specific CTLs

Arm I (temozolomide, CMV-specific T cells, surgery); Arm II (temozolomide, CMV-specific T cells)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (temozolomide, CMV-specific T cells, surgery); Arm II (temozolomide, CMV-specific T cells)

Temozolomide DRUG

Given PO

Also known as: CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temodal, Temodar, Temomedac, TMZ

Arm I (temozolomide, CMV-specific T cells, surgery); Arm II (temozolomide, CMV-specific T cells)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Arm I (temozolomide, CMV-specific T cells, surgery); Arm II (temozolomide, CMV-specific T cells)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent for the trial
• PHASE II DOSE EXPANSION IN RECURRENT GBM UNDERGOING RESECTION: Have histologically confirmed World Health Organization grade IV malignant glioma (glioblastoma or gliosarcoma); participants will also be eligible if the original histology was lower grade glioma and there is suspected transformation to glioblastoma based on imaging findings; if the final pathology report after resection fails to confirm recurrent glioblastoma or gliosarcoma, the subject will be followed for adverse events (AEs) and survival, but excluded for other primary and secondary objective analysis; the subject will be replaced
• PHASE II DOSE EXPANSION IN NEWLY DIAGNOSED GBM: Have histologically confirmed World Health Organization grade IV glioma (glioblastoma or gliosarcoma)
• PHASE II DOSE EXPANSION IN RECURRENT GBM UNDERGOING RESECTION: Be at first relapse; Note: relapse is defined as progression following initial therapy (i.e., radiation, chemotherapy, or radiation plus (+) chemotherapy); if the participant had a surgical resection for relapsed disease and no antitumor therapy instituted for up to 12 weeks, this is considered one relapse; for participants who had prior therapy for a lower grade glioma, the surgical diagnosis of glioblastoma or gliosarcoma will be considered first relapse
• PHASE II DOSE EXPANSION IN NEWLY DIAGNOSED GBM: Patients must have completed standard radiation therapy with concurrent temozolomide (TMZ) within 5 weeks (wks) of enrollment and must not have evidence of progressive disease on post treatment imaging; progression can only be defined using diagnostic imaging if there is new enhancement outside of the radiation field (beyond the high-dose region or 80% isodose line) or if there is unequivocal evidence of viable tumor on histopathologic sampling (e.g., solid tumor areas \[i.e,\> 70% tumor cell nuclei in areas\], high or progressive increase in mindbomb homolog 1\[MIB-1\] proliferation index compared with prior biopsy, or evidence for histologic progression or increased anaplasia in tumor); Note: given the difficulty of differentiating true progression from pseudoprogression, clinical decline alone, in the absence of radiographic or histologic confirmation of progression, will not be sufficient for definition of progressive disease in the first 12 weeks after completion of concurrent chemoradiotherapy
• PHASE II DOSE EXPANSION IN RECURRENT GBM UNDERGOING RESECTION: Have measurable disease consisting of a minimal volume of 1 cm\^3
• CMV seropositive
• PHASE I AND PHASE II DOSE EXPANSION IN RECURRENT GBM UNDERGOING RESECTION: Be willing to provide tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion
• PHASE II DOSE EXPANSION IN NEWLY DIAGNOSED GBM: Be willing to provide tissue from an archival tissue sample
• Have a performance status of \>= 60 on the Karnofsky performance status (KPS)
• If patient is on steroids, patient must be on a stable or decreasing dose of steroids for 5 days, no more than 2 mg dexamethasone (or equivalent) total per day at the time of screening and consent; if on steroids at the time of screening, the dose will need to be tapered and discontinued at least 5 days prior to CMV T cell infusion
• Absolute neutrophil count (ANC) \>= 1,500 /mcL (performed within 14 days \[+3 working days\] of treatment initiation)
• Platelets \>= 100,000 / mcL (performed within 14 days \[+3 working days\] of treatment initiation)
• Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L (performed within 14 days \[+3 working days\] of treatment initiation)
• Serum creatinine OR measured or calculated (creatinine clearance should be calculated per institutional standard) creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) =\< 1.5 X upper limit of normal (ULN) OR \>= 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN (performed within 14 days \[+3 working days\] of treatment initiation)

You may not qualify if:

• Has been treated previously with bevacizumab
• PHASE II DOSE EXPANSION IN RECURRENT GBM UNDERGOING RESECTION: Has tumor localized primarily to the posterior fossa, spinal cord, or an unresectable location
• Has received prior interstitial brachytherapy, implanted chemotherapy, or therapeutics delivered by local injection or convection enhanced delivery; prior treatment with Gliadel wafers will be excluded
• PHASE I AND PHASE II DOSE EXPANSION IN RECURRENT GBM UNDERGOING RESECTION: Is =\< 12 weeks from completing external beam radiotherapy; patients with proven progressive disease (PD) by resection or with new lesions outside of the radiation field should not be excluded even if they are within 12 weeks of external radiation therapy (XRT), per Response Assessment in Neuro-Oncology (RANO) criteria for early PD
• PHASE I AND PHASE II DOSE EXPANSION IN RECURRENT GBM UNDERGOING RESECTION: Is currently participating in a study of an investigational agent or using an investigational device for therapeutic purposes; concurrent use of Optune device is not allowed
• PHASE II DOSE EXPANSION IN NEWLY DIAGNOSED GBM: Is currently participating or has participated in any other newly diagnosed therapeutic trial before or after chemoradiation
• CMV seronegative
• Has a known history of human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies); human T-cell lymphotropic virus (HTLV) 1 antibody (HTLV1) and/or HTLV2; active hepatitis B (e.g., hepatitis B virus surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected); patients with prior hepatitis B virus (HBV) vaccination (anti-hepatitis B surface antibody \[HBs\] positive, HBsAg negative, anti-hepatitis B core antibody \[HBc\] negative) will NOT be excluded
• Has a diagnosis of immunodeficiency or is receiving systemic immunosuppressive therapy within 7 days of study entrance
• PHASE II DOSE EXPANSION IN RECURRENT GBM UNDERGOING RESECTION: Has had prior chemotherapy, or targeted small molecule therapy, within 2 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent; Note: subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study; Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
• PHASE II DOSE EXPANSION IN RECURRENT GBM UNDERGOING RESECTION: Has known gliomatous meningitis, subependymal spread, extracranial disease, or multifocal disease
• PHASE II DOSE EXPANSION IN NEWLY DIAGNOSED GBM: Has known gliomatous meningitis, extracranial disease, or multifocal disease
• Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study
• Has evidence of interstitial lung disease or active, non-infectious pneumonitis

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Glioma; Brain Neoplasms

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Shiao-Pei Weathers, MD, Associate Professor, Neuro-Oncology
• Organization: UT MD Anderson Cancer Center

sweathers@mdanderson.org

(713) 792-3906

Study Officials

• Shiao-Pei Weathers

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2016
• First Posted: January 22, 2016
• Study Start: June 1, 2016
• Primary Completion: February 23, 2022
• Study Completion: February 23, 2022
• Last Updated: June 18, 2023
• Results First Posted: June 18, 2023

Record last verified: 2023-05

Locations

US (1)