Grade IV Malignant GliomaPhase 1NCT01639612
Pilot Study of Bone Marrow/Stem Cells in Grade IV Malignant Glioma
A Phase 1 study testing ALD-451 in people with Grade IV Malignant Glioma, run by Henry Friedman at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Grade IV Malignant Glioma
- What is being tested?
- ALD-451
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2012to Apr 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
- Age ≥ 18 years of age.
- Karnofsky Performance Status ≥ 60%.
- Adequate renal function, defined as creatinine ≤ 1.3 mg/dL (μmol/L).
- Adequate serum chemistry parameters. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) and aspartate aminotransferase (AST) ≤ 2.5 X the ULN.
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
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- Women of childbearing potential must have a negative serum pregnancy test in the 48 hours prior to enrollment.
- 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.
- Is able to provide bone marrow sample from iliac crest.
- Is able to return for dosing two days post bone marrow harvest for infusion at Duke University.
- Is able to interrupt anticoagulation (if applicable) for bone marrow harvest and dosing procedures.
- 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.
- Patient must give written informed consent prior to any study-specific procedures being implemented.
- Is a good candidate for the trial, in the opinion of the investigator.
Who cannot join
- Primary WHO grade IV malignant glioma (glioblastoma or gliosarcoma) with an infratentorial lesion or involvement of the spinal cord.
- Patients with more than 1 cm of residual tumor in the maximal diameter at the post surgery MRI.
- Pregnant or lactating females.
- Women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception.
- 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.
- History of severe allergic reaction to contrast media.
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- Any serious medical condition or psychiatric illness unresponsive to medical intervention.
- 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.
- Myocardial infarction in the past 3 months.
- Mechanical heart valve.
- Medical history or neurological pathology that prevents neurocognitive testing and prescribed patient outcome reporting.
- Any concurrent illness or condition that in the opinion of the investigator might interfere with treatment or evaluation of safety and/or efficacy.
- Current or recent history of alcohol or drug abuse.
- Known history of infection with HIV or hepatitis.
- Active systemic infection requiring IV antibiotics.
- Subjects currently receiving restricted concomitant medications.
- Any previous or current treatment with angiogenic growth factors, cytokines, gene therapy or stem cell therapy.
- Unable to return for follow up visits for clinical evaluation, safety evaluation, laboratory studies, or MRI evaluation.
- Inability to undergo an MRI.
- Hemoglobin < 10g/dl.
- Platelet counts of < 100,000 or > 700,000 at screening.
- Hypertension with systolic BP ≥ 150mmHg or diastolic BP≥95 mmHg despite adequate anti-hypertensive treatment.
- Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study.
- Any previous or current treatment with stem cell therapy.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: A Pilot Safety Study of the Administration of Bone Marrow Derived Stem Cells (ALD-451) in WHO Grade IV Malignant Glioma
- 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.
Read the detailed description
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.
- Conditions
- Grade IV Malignant Glioma
- Being tested
- ALD-451
- Keywords
- Stem Cell, Grade IV Malignant Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALD-451Biological
ALD-451 iv
| Study group | Role | What they receive |
|---|---|---|
| ALD-451 | Experimental | Autologous bone marrow derived ALD-451 cells administered intravenously following surgery, radiation therapy and temozolomide Receives: Biological: ALD-451 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with unacceptable toxicity
Number of patients with irreversible Grade 3 or greater central nervous system (CNS) toxicity or Grade 3 or greater non-hematologic toxicity if attributable to ALD -451
Measured: 12 months after study drug administration
Secondary outcomes (2)
Number of ALD-451 cells recovered from bone marrow of patients following radiation therapy and chemotherapy
Measured: Baseline to 48 weeks
Neurocognition and patient-reported outcomes following ALD-451
Measured: Baseline to 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2012 (estimated)
- Study startJun 2012
- Primary completionMar 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Grade IV Malignant GliomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Henry Friedman
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Henry Friedman, Duke University
- Investigators
- Annick Desjardins, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01639612
- Sponsor's protocol ID
- Pro00031192
- Status last verified
- Apr 2016
- First submitted
- 28 Jun 2012
- Last updated
- 20 Apr 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Safety Study of the Administration of Bone Marrow Derived Stem Cells (ALD-451) in WHO Grade IV Malignant Glioma
- ClinicalTrials.gov ID
- NCT01639612
- Acronym / sponsor ID
- Pro00031192
- Conditions
- Grade IV Malignant Glioma
- Keywords
- Stem Cell, Grade IV Malignant Glioma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Henry FriedmanUniversity, hospital or other
- Study start
- Jun 2012
- Primary completion
- Mar 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 13 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- 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.
Detailed description
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ALD-451 | Experimental | Biological: ALD-451Autologous bone marrow derived ALD-451 cells administered intravenously following surgery, radiation therapy and temozolomide |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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).
- Age ≥ 18 years of age.
- Karnofsky Performance Status ≥ 60%.
- Adequate renal function, defined as creatinine ≤ 1.3 mg/dL (μmol/L).
- Adequate serum chemistry parameters. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) and aspartate aminotransferase (AST) ≤ 2.5 X the ULN.
Key exclusion criteria (24 listed)
- Primary WHO grade IV malignant glioma (glioblastoma or gliosarcoma) with an infratentorial lesion or involvement of the spinal cord.
- Patients with more than 1 cm of residual tumor in the maximal diameter at the post surgery MRI.
- Pregnant or lactating females.
- Women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ALD-451ALD-451 iv | Biological | ALD-451 |
Primary outcome
Number of patients with unacceptable toxicity
Time frame: 12 months after study drug administration
Number of patients with irreversible Grade 3 or greater central nervous system (CNS) toxicity or Grade 3 or greater non-hematologic toxicity if attributable to ALD -451
2 secondary outcomes
Number of ALD-451 cells recovered from bone marrow of patients following radiation therapy and chemotherapy
Time frame: Baseline to 48 weeks
Neurocognition and patient-reported outcomes following ALD-451
Time frame: Baseline to 48 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Annick Desjardins, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ALD-451 in people with Grade IV Malignant Glioma, run by Henry Friedman at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with unacceptable toxicity (time frame: 12 months after study drug administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2016.