Hematological MalignancyPhase 1NCT03885947
VPA Expanded UCB Transplantation for Treatment of Patients With Hematological Malignancies
A Phase 1 study testing Cord blood stem cells, Valproic Acid and Fludarabine in people with Hematological Malignancy and Acute Leukemia in Remission, run by Alla Keyzner at 1 site in United States.
Trial summary
In this Phase I study, the study team will evaluate the safety of Valproic Acid (VPA) expanded cord blood stem cells defined by the lack of serious infusion reactions or graft failure in patients with hematological malignancies undergoing umbilical cord blood transplantation. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hematological Malignancy, Acute Leukemia in Remission, Acute Lymphoblastic Leukemia in Remission
- What is being tested?
- Cord blood stem cells, Valproic Acid and Fludarabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Feb 2019to 10 Mar 2021
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Disease criteria:
- Patients with the following hematological malignancies:
- Acute Myeloid Leukemia (AML) in complete remission (CR)
- Acute Lymphoblastic Leukemia (ALL) in complete remission (CR)
- Myelodysplastic Syndrome (MDS) requiring intensive chemotherapy
- Non-Hodgkin lymphoma in complete or partial remission
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- Hodgkin lymphoma in complete or partial remission
- Age Criteria:
- 18 years up to 65 years.
- Organ Function and Performance Status Criteria:
- Performance status score: Karnofsky Score ≥60
- Adequate major organ function defined as:
- Left ventricular ejection fraction ≥40%
- Pulmonary function test demonstrating DLCO ≥50% predicted and corrected for hemoglobin
- Serum creatinine ≤ 2 mg/dL
- Transaminases ≤ 3x ULN
- Bilirubin ≤3x ULN except for in case of Gilbert's syndrome or ongoing hemolysis
- Ability to understand and the willingness to sign a written informed consent document
- Donor availability:
- -Lack of suitable HLA matched related or unrelated donor available within 30 days or less if BMT is urgent in the opinion of the transplant physician.
Who cannot join
- Progressive, persistent disease or active malignancy
- Greater than 10% blasts on bone marrow biopsy in patients with MDS
- Chemotherapy naïve
- History of myelofibrosis
- Presence of Bone Marrow Fibrosis grade 2/3
- Presence of donor specific anti-HLA antibodies against available UCB units at A, B, C or DR loci, with a mean fluorescence intensity (MFI)>1000
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- History of prior allogeneic stem cell transplantation
- Uncontrolled viral, bacterial or fungal infection
- History of HIV infection
- Presence of active CNS disease at the time of transplantation
- Pregnant or breastfeeding female
- Inability or unwillingness to use effective birth control.
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: Phase I Study of Valproic Acid Expanded Cord Blood Stem Cells as an Allogeneic Donor Source for Adults With Hematological Malignancies
In this Phase I study, the study team will evaluate the safety of Valproic Acid (VPA) expanded cord blood stem cells defined by the lack of serious infusion reactions or graft failure in patients with hematological malignancies undergoing umbilical cord blood transplantation. Moreover, the study team will also evaluate time to neutrophil and platelet engraftment as well as transplant related outcomes such as graft versus host disease (GVHD), treatment related mortality (TRM), and overall survival (OS).
Read the detailed description
This is a phase I trial for safety of VPA expanded cord blood stem cells in patients with hematological malignancies undergoing allogeneic stem cell transplantation. The primary endpoint of the study is safety as defined by the incidence of infusion reactions and graft failure, lack of neutrophil engraftment by day +42. The trial will consist of two cohorts. First cohort of 5-7 patients, will undergo double umbilical cord blood (UCB) transplantation. One UCB unit will undergo CD34 selection followed VPA based expansion. CD34 negative portion of that unit will be cryopreserved to be infused later following infusion of the expanded portion. Infusion of the second unmanipulated UCB will follow it. Preparative regimen is Fludarabine 150 mg/m2/Cytoxan 50 mg/m2/Thiotepa 10 mg/m2/TBI 400cGy.
Following successful engraftment in the first cohort, second cohort (10 patients) will only receive single manipulated unit.
Otherwise, patients will receive standard allogeneic stem cell transplantation care.
- Conditions
- Hematological Malignancy, Acute Leukemia in Remission, Acute Lymphoblastic Leukemia in Remission, Myelodysplastic Syndromes, Non-Hodgkin Lymphoma, Hodgkin Lymphoma
- Being tested
- Cord blood stem cells, Valproic Acid, Fludarabine, cytoxan, Thiotepa
- Keywords
- Hematological Malignancies, Expanded Umbilical Cord, Allogeneic Stem Cell Transplant, Leukemia, Lymphoma
- Medical subject headings
- Hematologic Neoplasms, Myelodysplastic Syndromes, Lymphoma, Non-Hodgkin, Hodgkin Disease, Leukemia, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cord blood stem cellsBiological
CD34 selected VPA expanded umbilical cord blood cells used in combination with or without unmanipulated umbilical cord blood .
Valproic AcidDrug
Also called VPA
Valproic Acid (VPA) expanded cord blood stem cells
FludarabineDrug
Fludarabine 150 mg/m2
cytoxanDrug
Cytoxan 50 mg/m2
ThiotepaDrug
Thiotepa 10 mg/m2
TBIBiological
TBI 400cGy
| Study group | Role | What they receive |
|---|---|---|
| VPA expanded cord blood stem cells | Experimental | CD34 selected VPA expanded umbilical cord blood cells used in combination with or without unmanipulated umbilical cord blood for patients with hematological malignancies undergoing allogeneic stem cell transplantation.
VPA expanded cord blood stem cells in patients with hematological malignancies undergoing allogeneic stem cell transplantation Receives: Biological: Cord blood stem cells; Drug: Valproic Acid; Drug: Fludarabine; Drug: cytoxan; Drug: Thiotepa; Biological: TBI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Infusion Reaction
Safety as measured by the incidence of infusion related reactions.
Measured: 42 days
Number of Graft Failure
Safety as measured by the incidence of graft failures.
Measured: 42 days
Secondary outcomes (10)
Time to neutrophil engraftment
Transplant related outcomes: time to neutrophil engraftment
Measured: 1 year
Time to platelets engraftment
Transplant related outcomes: time to platelets engraftment
Measured: 1 year
Number of transplant-related mortality (TRM)
Transplant related outcomes: transplant-related mortality (TRM)
Measured: 1 year
Number of disease free survivals
Transplant related outcomes: Number of disease free survivals
Measured: 1 year
Number of overall survivals
Transplant related outcomes: Number of overall survivals
Measured: 1 year
Number of participants at risk of GVHD
Transplant Related Outcomes: risk of GVHD
Measured: 1 year
Number of infectious complications
Transplant Related Outcomes: incidence of infectious complications - which is any documented bacterial, viral, or fungal infections.
Measured: 1 year
Time to myeloid engraftment
Assess the kinetics of engraftment and immune reconstitution by assessing time to myeloid engraftment
Measured: 42 days
Time to lymphoid engraftment
Assess the kinetics of engraftment and immune reconstitution by assessing time to lymphoid engraftment
Measured: 42 days
Change in T cell count
Assess the kinetics of engraftment and immune reconstitution by assessing the T cell count at 42 days as compared to baseline
Measured: Baseline and 42 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2019
- Study start21 Feb 2019
- Primary completion10 Mar 2021
- Study completion10 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematological MalignancyStudies 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- Open label single arm
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alla Keyzner
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Alla Keyzner, Icahn School of Medicine at Mount Sinai
- Investigators
- Alla Keyzner, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03885947
- Sponsor's protocol ID
- GCO 14-0451
- Status last verified
- May 2021
- First submitted
- 20 Mar 2019
- Last updated
- 24 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Valproic Acid Expanded Cord Blood Stem Cells as an Allogeneic Donor Source for Adults With Hematological Malignancies
- ClinicalTrials.gov ID
- NCT03885947
- Acronym / sponsor ID
- GCO 14-0451
- Conditions
- Hematological Malignancy, Acute Leukemia in Remission, Acute Lymphoblastic Leukemia in Remission, Myelodysplastic Syndromes, Non-Hodgkin Lymphoma, Hodgkin Lymphoma
- Keywords
- Hematological Malignancies, Expanded Umbilical Cord, Allogeneic Stem Cell Transplant, Leukemia, Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Alla KeyznerUniversity, hospital or other
- Study start
- 21 Feb 2019 (actual)
- Primary completion
- 10 Mar 2021 (actual)
- Study completion
- 10 Mar 2021 (actual)
- First posted
- 22 Mar 2019 (actual)
- 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.
In this Phase I study, the study team will evaluate the safety of Valproic Acid (VPA) expanded cord blood stem cells defined by the lack of serious infusion reactions or graft failure in patients with hematological malignancies undergoing umbilical cord blood transplantation. Moreover, the study team will also evaluate time to neutrophil and platelet engraftment as well as transplant related outcomes such as graft versus host disease (GVHD), treatment related mortality (TRM), and overall survival (OS).
Detailed description
This is a phase I trial for safety of VPA expanded cord blood stem cells in patients with hematological malignancies undergoing allogeneic stem cell transplantation. The primary endpoint of the study is safety as defined by the incidence of infusion reactions and graft failure, lack of neutrophil engraftment by day +42. The trial will consist of two cohorts. First cohort of 5-7 patients, will undergo double umbilical cord blood (UCB) transplantation. One UCB unit will undergo CD34 selection followed VPA based expansion. CD34 negative portion of that unit will be cryopreserved to be infused later following infusion of the expanded portion. Infusion of the second unmanipulated UCB will follow it. Preparative regimen is Fludarabine 150 mg/m2/Cytoxan 50 mg/m2/Thiotepa 10 mg/m2/TBI 400cGy.
Following successful engraftment in the first cohort, second cohort (10 patients) will only receive single manipulated unit.
Otherwise, patients will receive standard allogeneic stem cell transplantation care.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open label single arm
| Arm | Type | Receives |
|---|---|---|
| VPA expanded cord blood stem cells | Experimental | Biological: Cord blood stem cells, Drug: Valproic Acid, Drug: Fludarabine, Drug: cytoxan, Drug: Thiotepa, Biological: TBICD34 selected VPA expanded umbilical cord blood cells used in combination with or without unmanipulated umbilical cord blood for patients with hematological malignancies undergoing allogeneic stem cell transplantation. VPA expanded cord blood stem cells in patients with hematological malignancies undergoing allogeneic stem cell transplantation |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Acute Myeloid Leukemia (AML) in complete remission (CR)
- Acute Lymphoblastic Leukemia (ALL) in complete remission (CR)
- Myelodysplastic Syndrome (MDS) requiring intensive chemotherapy
- Non-Hodgkin lymphoma in complete or partial remission
- Hodgkin lymphoma in complete or partial remission
Key exclusion criteria (12 listed)
- Progressive, persistent disease or active malignancy
- Greater than 10% blasts on bone marrow biopsy in patients with MDS
- Chemotherapy naïve
- History of myelofibrosis
- Presence of Bone Marrow Fibrosis grade 2/3
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 |
|---|---|---|
| Cord blood stem cellsCD34 selected VPA expanded umbilical cord blood cells used in combination with or without unmanipulated umbilical cord blood . | Biological | VPA expanded cord blood stem cells |
| Valproic AcidAlso: VPAValproic Acid (VPA) expanded cord blood stem cells | Drug | VPA expanded cord blood stem cells |
| FludarabineFludarabine 150 mg/m2 | Drug | VPA expanded cord blood stem cells |
| cytoxanCytoxan 50 mg/m2 | Drug | VPA expanded cord blood stem cells |
| ThiotepaThiotepa 10 mg/m2 | Drug | VPA expanded cord blood stem cells |
| TBITBI 400cGy | Biological | VPA expanded cord blood stem cells |
Primary outcome
Number of Infusion Reaction
Time frame: 42 days
Safety as measured by the incidence of infusion related reactions.
Number of Graft Failure
Time frame: 42 days
Safety as measured by the incidence of graft failures.
10 secondary outcomes
Time to neutrophil engraftment
Time frame: 1 year
Time to platelets engraftment
Time frame: 1 year
Number of transplant-related mortality (TRM)
Time frame: 1 year
Number of disease free survivals
Time frame: 1 year
Number of overall survivals
Time frame: 1 year
Number of participants at risk of GVHD
Time frame: 1 year
Number of infectious complications
Time frame: 1 year
Time to myeloid engraftment
Time frame: 42 days
Time to lymphoid engraftment
Time frame: 42 days
Change in T cell count
Time frame: Baseline and 42 days
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 24 May 2021.
- Individual participant dataSharing planned: No
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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.
Alla Keyzner, MD principal investigator
Icahn School of Medicine at Mount Sinai
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 Cord blood stem cells, Valproic Acid and Fludarabine in people with Hematological Malignancy and Acute Leukemia in Remission, run by Alla Keyzner 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 20 inclusion and 12 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 24 May 2021. 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 Infusion Reaction (time frame: 42 days). The study lists 2 primary outcomes in all. 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 24 May 2021.