Grade IV Malignant Glioma Clinical Trial
Official title:
A Pilot Safety Study of the Administration of Bone Marrow Derived Stem Cells (ALD-451) in WHO Grade IV Malignant Glioma
1. Purpose of the Study - This protocol aims to demonstrate the feasibility and safety of autologous ALD-451 cells administered intravenously in World Health Organization (WHO) grade IV malignant glioma patients following surgery, radiation therapy and temozolomide; as well as to obtain an initial description of the effects of ALD-451 cells on neuro-cognition allowing the design of a subsequent phase 2 trial of this intervention in patients with malignant glioma. The primary objective of this study is to demonstrate the safety of intravenously administered autologous bone marrow derived ALD-451 cells in the brain following surgery, radiation therapy and temozolomide in patients with WHO grade IV malignant glioma. The secondary objective of this study is to determine the recovery of ALD-451 from bone marrow of patients following radiation therapy and temozolomide. The exploratory objective of this study is to determine if intravenous administration of autologous ALD-451 cells following surgery, radiation therapy and temozolomide in WHO grade IV malignant glioma patients may have an effect on subsequent deterioration of neurocognition and patient-reported outcomes.
This is a pilot, open label study in which eligible subjects will undergo surgery, radiation
therapy, Temozolomide, bone marrow harvest, MRIs, and intravenous infusion of ALD-451. The
subjects will be followed via the safety and efficacy procedures completed during visits
over 12 months.
Two to 8 weeks following gross total resection (GTR), patients with WHO grade IV malignant
glioma that have agreed to participate in the study by signing the informed consent will
undergo screening procedures to determine eligibility. Once enrolled on the study, baseline
neurocognitive testing will be performed. Two to 8 weeks after enrolled subjects have
completed the 6 -6 ½ weeks of radiation therapy and daily temozolomide, subjects will have
their bone marrow harvested by undergoing a bone marrow aspiration with 160 (+/-20) mL of
bone marrow collected from the iliac crest (one to 2 days after the patient has been
re-assessed for continued eligibility).
The sample will be transported to the Robertson CT2 GMP Facility where ALD-451 will be
manufactured and the ALD-451 product returned to the Investigational Chemotherapy Services
for infusion. A small aliquot of ALD-451 will be taken from the starting bone marrow,
de-identified, labeled with the manufacturing lot number, and stored at Duke University for
the duration of the trial to support ongoing studies determining potency of the product. For
all ALD-451 products, a retained aliquot that is the equivalent of 10 mls of the starting
bone marrow will be cryopreserved and stored in the vapor phase of liquid nitrogen. Harvest
of 160 mL of subject bone marrow will allow for retains without excessive reduction in the
anticipated ALDHbr dose. These frozen retains will be used for product characterization and
development of a potency assay. These aliquots will not be used for any other purposes and
any remaining aliquots will be destroyed at the time of Biologics License Application (BLA)
approval.
Two - four days after having bone marrow harvested for ALDHbr cells, ALD-451 will be
administered through a peripheral IV, up to 1 hour. This will be followed by 4 hours of IV
fluids and observation. Normal Saline will be used as the IV fluids and will be initiated a
few minutes before the administration of ALD-451. The bag within which ALD-451 will be
received will be flushed once with 10 ml of Normal Saline and the fluid obtained after
flushing the bag will be administered to the patient, to assure that the investigators have
reinfused in the patient the vast majority of the ALD-451 present in the bag.
Temozolomide will be reinitiated four weeks after completion of radiation therapy and daily
Temozolomide (at least two weeks after ALD-451 infusion). Temozolomide will be dosed at 150
mg/m2 orally on days 1-5 of a 28-day cycle for the first cycle and 200 mg/m2 orally for the
following 11 cycles. Patients will receive a total of 12 cycles of Temozolomide following
completion of radiation therapy.
Neurocognitive testing and patient-reported outcomes will be obtained at study enrollment,
two weeks after completion of radiation therapy and temozolomide and after six and twelve
cycles of temozolomide.
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Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care