View Clinical Trial (Medical Research Study)
A Pilot Safety Study of the Administration of Bone Marrow Derived Stem Cells (ALD-451) in WHO Grade IV Malignant Glioma
| City: |
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Durham |
| State: |
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North Carolina |
| Zip Code: |
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27710 |
| Conditions: |
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Grade IV Malignant Glioma |
| Purpose: |
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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 Aldagen where ALD 451 will be manufactured and the ALD-451
product returned to the investigational site via a courier. 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 Aldagen 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 if none of the
informational testing performed during IS-001 correlates with patient outcome or is
stability indicating. 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.
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| Study Summary: |
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| Criteria: |
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Inclusion Criteria:
Inclusion Criteria are as follows:
1. Newly diagnosed patients with histologically proven supratentorial primary WHO grade
IV malignant glioma (glioblastoma or gliosarcoma) with gross total resection (less
than 1 cm of residual disease in the maximal diameter).
2. Age ≥ 18 years of age.
3. Karnofsky Performance Status ≥ 60%.
4. Adequate renal function, defined as creatinine ≤ 1.3 mg/dL (μmol/L).
5. Adequate serum chemistry parameters. Total bilirubin ≤ 1.5 x ULN and AST ≤ 2.5 X the
ULN.
6. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
7. Women of childbearing potential must have a negative serum pregnancy test in the 48
hours prior to enrollment.
8. Men and women of reproductive potential must agree to use an effective contraceptive
method including one of the following: surgical sterilization (tubal ligation for
women or vasectomy for men); approved hormonal contraceptives (such as birth control
pills, patches, implants or injections); barrier methods (such as condom or
diaphragm) used with a spermicidal cream or an intrauterine device (IUD).
Contraceptive measures such as Plan B ™, sold for emergency use after unprotected
sex, are not acceptable methods for routine use.
9. Is able to provide bone marrow sample from iliac crest.
10. Is able to return for dosing two days post bone marrow harvest for infusion at Duke
University.
11. Is able to interrupt anticoagulation (if applicable) for bone marrow harvest and
dosing procedures.
12. Patient willing to undergo external beam radiation therapy and chemotherapy with
Temozolomide at Duke University Medical Center and stay four hours post infusion of
ALD-451.
13. Patient must give written informed consent prior to any study-specific procedures
being implemented.
14. Is a good candidate for the trial, in the opinion of the investigator.
Exclusion Criteria:
Exclusion Criteria are as follows:
1. Primary WHO grade IV malignant glioma (glioblastoma or gliosarcoma) with an
infratentorial lesion or involvement of the spinal cord.
2. Patients with more than 1 cm of residual tumor in the maximal diameter at the post
surgery MRI.
3. Pregnant or lactating females.
4. Women of childbearing potential and men who are sexually active and not willing/able
to use medically acceptable forms of contraception.
5. Prior chemotherapy, immunotherapy, biologic therapy, radiation therapy,
radioimmunotherapy, hormonal therapy, or experimental therapy for brain tumor. Prior
or active corticosteroid therapy is permitted to control neurologic symptoms due to
intracranial edema.
6. History of severe allergic reaction to contrast media.
7. Any serious medical condition or psychiatric illness unresponsive to medical
intervention.
8. Prior malignancy if active treatment was required during the previous 5 years except
for adequately treated basal cell or squamous cell skin cancer and in situ uterine
cervical cancer.
9. Myocardial infarction in the past 3 months.
10. Mechanical heart valve.
11. Medical history or neurological pathology that prevents neurocognitive testing and
prescribed patient outcome reporting.
12. Any concurrent illness or condition that in the opinion of the investigator might
interfere with treatment or evaluation of safety and/or efficacy.
13. Current or recent history of alcohol or drug abuse.
14. Known history of infection with HIV or hepatitis.
15. Active systemic infection requiring IV antibiotics.
16. Subjects currently receiving restricted concomitant medications.
17. Any previous or current treatment with angiogenic growth factors, cytokines, gene
therapy or stem cell therapy.
18. Unable to return for follow up visits for clinical evaluation, safety evaluation,
laboratory studies, or MRI evaluation.
19. Inability to undergo an MRI.
20. Hemoglobin < 10g/dl.
21. Uncorrected coagulopathy as defined as INR > 1.4; PTT > 35sec.
22. Platelet counts of < 100,000 or > 700,000 at screening.
23. Hypertension with SBP ≥ 150mmHg or DBP≥95 mmHg despite adequate anti-hypertensive
treatment.
24. Patients treated on any other therapeutic clinical protocols within 30 days prior to
study entry or during participation in the study.
25. Any previous or current treatment with stem cell therapy.
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| NCT ID: |
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NCT01639612 |
| Primary Contact: |
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Principal Investigator
Annick Desjardins, MD
Duke University
Stevie Threatt
Phone: 919-684-3657
Email: stevie.threatt@duke.edu
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| Backup Contact: |
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N/A |
| Location Contact: |
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Durham, North Carolina 27710
United States
Stevie Threatt
Phone: 919-684-3657
Email: stevie.threatt@duke.edu
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 19, 2013 |
| Modifications to this listing: |
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