Pilot Study of Bone Marrow/Stem Cells in Grade IV Malignant Glioma

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Duke University
Sponsor:
Information provided by (Responsible Party):
Henry Friedman, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT01639612
First received: June 28, 2012
Last updated: May 1, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Grade IV Malignant Glioma
Biological: ALD-451
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 12
Study Start Date: June 2012
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ALD-451 Biological: ALD-451
ALD-451 iv

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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. Platelet counts of < 100,000 or > 700,000 at screening.
  22. Hypertension with SBP ≥ 150mmHg or DBP≥95 mmHg despite adequate anti-hypertensive treatment.
  23. Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study.
  24. Any previous or current treatment with stem cell therapy.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01639612

Contacts
Contact: Stevie Threatt 919-684-3657 stevie.threatt@duke.edu

Locations
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Stevie Threatt    919-684-3657    stevie.threatt@duke.edu   
Contact: Susan Boulton, RN    919-668-0896    susan.boulton@duke.edu   
Principal Investigator: Annick Desjardins, MD, FRCPC         
Sponsors and Collaborators
Henry Friedman
Investigators
Principal Investigator: Annick Desjardins, MD Duke University
  More Information

No publications provided

Responsible Party: Henry Friedman, Professor of Pediatrics, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT01639612     History of Changes
Other Study ID Numbers: Pro00031192
Study First Received: June 28, 2012
Last Updated: May 1, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Duke University:
Stem Cell
Grade IV Malignant Glioma

Additional relevant MeSH terms:
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on July 29, 2014