Pilot Study of Bone Marrow/Stem Cells in 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 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 objectives of this study are the following: to determine the recovery of ALD-451 from bone marrow of patients following radiation therapy and temozolomide; 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.
One to two 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 weeks after enrolled subjects have completed the 6 -6 ½ weeks of radiation therapy and daily temozolomide, subjects will be re-assessed to make certain they still meet eligibility criteria. If the subject is still eligible to participate, on the following day, they will have their bone marrow harvested by undergoing a bone marrow aspiration with 160 (+/-20) mL of bone marrow collected from the iliac crest.
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 Chemo 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 retain 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 (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.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
|Official Title:||A Pilot Safety Study of the Administration of Bone Marrow Derived Stem Cells (ALD-451) in WHO Grade IV Malignant Glioma|
- Number of patients with unacceptable toxicity [ Time Frame: 12 months after study drug administration ] [ Designated as safety issue: Yes ]Number of patients with irreversible Grade 3 or greater CNS toxicity or Grade 3 or greater non-hematologic toxicity if attributable to ALD -451
- Number of ALD-451 cells recovered from bone marrow of patients following radiation therapy and chemotherapy [ Time Frame: Baseline to 24 weeks ] [ Designated as safety issue: No ]
- Neurocognition and patient-reported outcomes following ALD-451 [ Time Frame: Baseline to 24 weeks ] [ Designated as safety issue: No ]
- Number of ALD-451 cells recovered from bone marrow of patients following radiation therapy and chemotherapy [ Time Frame: Baseline to 48 weeks ] [ Designated as safety issue: No ]
- Neurocognition and patient-reported outcomes following ALD-451 [ Time Frame: Baseline to 48 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||June 2012|
|Estimated Primary Completion Date:||May 2016 (Final data collection date for primary outcome measure)|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01639612
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||Annick Desjardins, MD||Duke University|