Radiation/Temozolomide and Immunotherapy With Daratumumab to Improve Antitumor Efficacy in Glioblastoma

NCT04922723 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2109412076IND# Pending
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

TMZ is a standard therapy for GBM. The study will demonstrate that Daratumumab can collaborate with TMZ to enhance the cytotoxicity against GBM cells. Collectively, the preclinical data along with existing in vivo studies by others provides the rationale for therapeutic targeting of CD38 in GBM and its microenvironment. Daratumumab is commercially available, is safe and well tolerated when combined with alkylating chemotherapy, radiation therapy and has attained therapeutic CSF levels. Thus, the addition of Daratumumab to the frontline treatment regimen of GBM can potentially have a significant clinical benefit. Approximately 16 subjects will be enrolled in this trial. Up to 6 will be enrolled in the phase I part and 10 to 13 in the phase II part to come up with a total of 16 patients with 2 phases combined.

Conditions

Glioblastoma

Keywords

Immunotherapy; Radiation/Temozolomide; Antitumor Efficacy

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicity (DLT) rate of Daratumumab

  Rate of subjects that experience DLT. Subjects will be evaluated for DLTs after 6 doses of Daratumumab. If there is no DLT in the first 3 patients, the investigators will move forward to conduct the phase II clinical trial. If there is a DLT, another three patients will be enrolled. The study may be suspended with additional discussions in the data monitoring committee if there are ≥2 identified DLTs in the first 3 patients or ≥2 DLTs in the first 6 patients. The sample size justification is based on the standard 3+3 design.

  Up to 6 weeks

• Phase II - Median overall survival of newly diagnosed GBM patients

  Evaluate the median overall survival of newly diagnosed GBM patients. All patients in phase I part will be included in the efficacy analysis on overall survival (OS) in phase II part. If the 1-year survival rate of the study subjects is above 50% (median survival rate), it will be considered that the new intervention is promising.

  Up to 12 months

Secondary Outcomes (7)

• Phase I - Median overall survival of newly diagnosed GBM patients

  Up to 6 weeks

• Phase I - Evaluate the Progression-Free Survival (PFS)

  Up to 6 weeks

• Phase I - Assess the treatment-emergent adverse events

  Up to 6 weeks

• Phase I - Estimate the tumor response rate

  Up to 6 weeks

• Phase II - Evaluate the Progression-Free Survival (PFS)

  Up to 12 months

Study Arms (1)

Daratumumab

EXPERIMENTAL

Daratumumab, IV, 16 mg/KG - 1 dose prior to surgery or biopsy; Weeks 1 - 8 = 1 dose weekly; Weeks 9 - 24 = 1 dose every other week; Weeks 25 onward (determined by disease progression) = 1 dose every 4 weeks

Drug: Daratumumab

Interventions

Daratumumab DRUG

Daratumumab will be administered by IV infusion to subjects in combination with current therapeutic strategies of surgical resection followed by a course of Temozolomide and radiation therapy.

Also known as: Darzalex

Daratumumab

Eligibility Criteria

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

You may qualify if:

• Subjects must have high radiological likelihood of GBM with plan for resection/biopsy for histologically confirmed GBM
• ECOG Performance status ≤ 2
• Subjects must have normal organ and marrow function as defined below:
• Leukocytes ≥ 3,000/mcL
• Absolute neutrophil count ≥ 1,500/mcL
• Platelet count ≥ 100,000/mcL
• Total bilirubin within normal institutional limits
• AST (SGOT) ≤ 3 X institutional upper limit of normal
• ALT (SGPT) ≤ 3 X institutional upper limit of normal
• Serum Creatinine within normal institutional limits OR glomerular filtration rate (GFR) 60 mL/min/1.73 m2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m2
• The effects of Daratumumab on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
• Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of Daratumumab and TMZ administration.
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

You may not qualify if:

• Patients who received prior treatment for GBM.
• Patients who are receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Daratumumab and TMZ.
• BCG (Intravesical), Deferiprone, and Dipyrone are risk X category and should be avoided when Daratumumab is used. Chloramphenicol (Ophthalmic), promazine and Clozapine are in the risk category C and myelosuppression signs should be monitored when used in combination with Daratumumab.
• Avoid category Risk X drugs such as BCG (Intravesical), Deferiprone, Dipyrone, Natalizumab, Tacrolimus (Topical), Vaccines (Live) and Pimecrolimus concurrently with TMZ. Consider therapy modifications of category D drugs such as Baricitinib, Echinacea, Fingolimod, Leflunomide, Lenograstim, Lipegfilgrastim, Nivolumab, Palifermin, Roflumilast, Tofacitinib, Vaccines (Inactivated when used with TMZ. Monitor therapy for category risk C drugs such as Chloramphenicol (Ophthalmic), CloZAPine, Coccidioides immitis Skin Test, Denosumab, Ocrelizumab, Pidotimod, Promazine, Sipuleucel-T, Trastuzumab, and Valproate Products.
• Patients with uncontrolled intercurrent illness.
• Patients with psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because there are no animal and human data to assess the risk of Daratumumab during pregnancy. On the other hand, TMZ is a category D drug where adverse events are observed in animal reproduction studies. May cause fetal harm when administered to pregnant females. Male and female patients should use effective contraception to avoid pregnancy while receiving temozolomide. May impair male fertility based on animal data).
• Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) \<50% of predicted normal.
• o Note that FEV1 testing is required for participants suspected of having COPD and participants must be excluded if FEV1 is \<50% of predicted normal.
• Moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification.
• o Note that participants who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate in the study.
• Clinically significant cardiac disease, including:
• Myocardial infarction within 6 months before randomization, or unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV).
• Uncontrolled cardiac arrhythmia

Sponsors & Collaborators

• West Virginia University: lead

Study Sites (1)

West Virginia University Cancer Institute Mary Babb Randolph Cancer Center

Morgantown, West Virginia, 26506, United States

Location

Related Publications (1)

• Norouzi S, Aulakh S. CD38 overexpression drives glioblastoma progression via L1CAM/ICAM1/JAK-STAT-Driven tumor microenvironment rewiring. Transl Oncol. 2026 Apr 6;67:102758. doi: 10.1016/j.tranon.2026.102758. Online ahead of print.

  PMID: 41946147 DERIVED

MeSH Terms

Conditions

Glioblastoma

Interventions

daratumumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Sonikpreet Aulakh, MD

  WVU Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: June 8, 2021
• First Posted: June 11, 2021
• Study Start: October 3, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 28, 2026

Record last verified: 2026-04

Locations

US (1)