Acute Biphenotypic LeukemiaPhase 1NCT02529813
CD19-Specific T-cells in Treating Patients With Advanced Lymphoid Malignancies
A Phase 1 study testing Cyclophosphamide, Fludarabine Phosphate and Laboratory Biomarker Analysis in people with Acute Biphenotypic Leukemia and Acute Lymphoblastic Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase I clinical trial studies the side effects and best dose of CD19-specific T-cells in treating patients with lymphoid malignancies that have spread to other places in the body and usually cannot be cured or controlled with treatment. Read more about this study
- Who is it for?
- Ages 1 year to 80 years
- Conditions the study is for
- Acute Biphenotypic Leukemia, Acute Lymphoblastic Leukemia, Blasts 5 Percent or More of Bone Marrow Nucleated Cells
- What is being tested?
- Cyclophosphamide, Fludarabine Phosphate and Laboratory Biomarker Analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Dec 2015to 8 Nov 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 1 year to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with a history of CD19+ lymphoid malignancy defined as acute lymphoblastic leukemia, acute biphenotypic leukemia, non-Hodgkin's lymphoma, small lymphocytic lymphoma, or chronic lymphocytic leukemia with active disease defined by presence of > 5% malignant blasts in bone marrow and/or peripheral blood, and/or minimal residual disease by flow cytometry or molecular analysis for fusion proteins, and/or positive imaging for extramedullary disease; patients must have measurable disease at time of study treatment
- Confirmed history of CD19 positivity by flow cytometry for malignant cells
- Lansky/Karnofsky performance scale > 60%
- Patient able to provide written informed consent; parent or guardian of minor patient able to provide written informed consent
- Patient able to provide written informed consent for the long-term follow-up gene therapy study: 2006-0676; parent or guardian of minor patient able to provide written informed consent for the long-term follow-up gene therapy study: 2006-0676
Who cannot join
- Positive beta human chorionic gonadotropin (HCG) in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization or lactating females
- Patients with known allergy to bovine or murine products
- Positive serology for human immunodeficiency virus (HIV)
- Active hepatitis B or active hepatitis C
- Has received donor lymphocyte infusion (DLI) product within 6 weeks of CAR T cell infusion
- Has received allogeneic hematopoietic stem cell transplant within 3 months of CAR T cell infusion; hematopoietic stem cell transplant (HSCT) > 3 months from CAR T cell infusion eligible
Trial locations and contacts
1 site in 1 country.
About this study
Official title: CD19+ Chimeric Antigen Receptor T Cells for Patients With Advanced Lymphoid Malignancies
This phase I clinical trial studies the side effects and best dose of CD19-specific T-cells in treating patients with lymphoid malignancies that have spread to other places in the body and usually cannot be cured or controlled with treatment. Sometimes researchers change the deoxyribonucleic acid (DNA) (genetic material in cells) of donated T-cells (white blood cells that support the immune system) using a process called "gene transfer." Gene transfer involves drawing blood from the patient, and then separating out the T-cells using a machine. Researchers then perform a gene transfer to change the T-cells' DNA, and then inject the changed T-cells into the body of the patient. Injecting modified T-cells made from the patient may help attack cancer cells in patients with advanced B-cell lymphoma or leukemia.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the safety and maximum tolerated dose of genetically modified, CD19-specific T cells administered into patients with CD19+ advanced lymphoid malignancies.
SECONDARY OBJECTIVES:
- To screen for the development of host immune responses against the CD19-specific chimeric antigen receptor (CAR).
II. To describe the homing ability of the infused T cells. III. To assess disease response. IV. To determine persistence of CAR+ T cells.
OUTLINE: This is a dose escalation study of CD19 positive chimeric antigen receptor T-cells.
LYMPHODEPLETING CHEMOTHERAPY: Patients may receive standard chemotherapy comprised of fludarabine phosphate intravenously (IV) over 1 hour and cyclophosphamide IV over 3 hours on days -5 to -3 or cyclophosphamide IV every 12 hours on days -5 to -3 at the discretion of the treating physician.
Within 30 days post completion of lymphodepletion, patients receive CD19 positive chimeric antigen receptor T-cells IV over 15-30 minutes on day 0, or split into two portions on days 0 and 1.
After completion of study treatment, patients are followed up for at least 15 years.
- Conditions
- Acute Biphenotypic Leukemia, Acute Lymphoblastic Leukemia, Blasts 5 Percent or More of Bone Marrow Nucleated Cells, CD19 Positive, Minimal Residual Disease, Non-Hodgkin Lymphoma
- Being tested
- Cyclophosphamide, Fludarabine Phosphate, Laboratory Biomarker Analysis, Tisagenlecleucel
- Medical subject headings
- Leukemia, Biphenotypic, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Neoplasm, Residual, Lymphoma, Non-Hodgkin, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida
Given IV
Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
TisagenlecleucelBiological
Also called CART-19, CART19, CTL019, CTL019 T-cells
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Arm I (CD19 positive chimeric antigen receptor T-cells) | Experimental | LYMPHODEPLETING CHEMOTHERAPY: Patients may receive standard chemotherapy comprised of fludarabine phosphate IV over 1 hour and cyclophosphamide IV over 3 hours on days -5 to -3 or cyclophosphamide IV every 12 hours on days -5 to -3 at the discretion of the treating physician.
Within 30 days post completion of lymphodepletion, patients receive CD19 positive chimeric antigen receptor T-cells IV over 15-30 minutes on day 0, or split into two portions on days 0 and 1. Receives: Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Biological: Tisagenlecleucel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of genetically modified, CD19-specified T cells
Will be defined as the highest dose for which the posterior probability of toxicity is closest to 25%. Demographic and clinical characteristics will be summarized using descriptive statistics by dose level. The number of patients with dose limiting toxicities will be reported at each dose level.
Measured: Up to 30 days
Secondary outcomes (2)
The proportion of patients for which a T cell product could not be prepared
Computed with a corresponding 95% confidence interval.
Measured: Up to 1 year
Proportion of patients experiencing response (complete response and partial response)
Estimated with a corresponding 95% confidence interval.
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2015 (estimated)
- Study start16 Dec 2015
- Primary completion8 Nov 2021
- Study completion8 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Biphenotypic LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- 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
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Ziopharm Oncology
- Responsible party
- Sponsor
- Investigators
- Partow Kebriaei, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02529813
- Sponsor's protocol ID
- 2013-1018
- Other IDs
- NCI-2015-01492, 20152145, 1159157, 2013-1018
- Status last verified
- Jun 2022
- First submitted
- 18 Aug 2015
- Last updated
- 30 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CD19+ Chimeric Antigen Receptor T Cells for Patients With Advanced Lymphoid Malignancies
- ClinicalTrials.gov ID
- NCT02529813
- Acronym / sponsor ID
- 2013-1018
- Conditions
- Acute Biphenotypic Leukemia, Acute Lymphoblastic Leukemia, Blasts 5 Percent or More of Bone Marrow Nucleated Cells, CD19 Positive, Minimal Residual Disease, Non-Hodgkin Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Ziopharm Oncology
- Study start
- 16 Dec 2015 (actual)
- Primary completion
- 8 Nov 2021 (actual)
- Study completion
- 8 Nov 2021 (actual)
- First posted
- 20 Aug 2015 (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.
This phase I clinical trial studies the side effects and best dose of CD19-specific T-cells in treating patients with lymphoid malignancies that have spread to other places in the body and usually cannot be cured or controlled with treatment. Sometimes researchers change the deoxyribonucleic acid (DNA) (genetic material in cells) of donated T-cells (white blood cells that support the immune system) using a process called "gene transfer." Gene transfer involves drawing blood from the patient, and then separating out the T-cells using a machine. Researchers then perform a gene transfer to change the T-cells' DNA, and then inject the changed T-cells into the body of the patient. Injecting modified T-cells made from the patient may help attack cancer cells in patients with advanced B-cell lymphoma or leukemia.
Detailed description
PRIMARY OBJECTIVES:
- To determine the safety and maximum tolerated dose of genetically modified, CD19-specific T cells administered into patients with CD19+ advanced lymphoid malignancies.
SECONDARY OBJECTIVES:
- To screen for the development of host immune responses against the CD19-specific chimeric antigen receptor (CAR).
II. To describe the homing ability of the infused T cells. III. To assess disease response. IV. To determine persistence of CAR+ T cells.
OUTLINE: This is a dose escalation study of CD19 positive chimeric antigen receptor T-cells.
LYMPHODEPLETING CHEMOTHERAPY: Patients may receive standard chemotherapy comprised of fludarabine phosphate intravenously (IV) over 1 hour and cyclophosphamide IV over 3 hours on days -5 to -3 or cyclophosphamide IV every 12 hours on days -5 to -3 at the discretion of the treating physician.
Within 30 days post completion of lymphodepletion, patients receive CD19 positive chimeric antigen receptor T-cells IV over 15-30 minutes on day 0, or split into two portions on days 0 and 1.
After completion of study treatment, patients are followed up for at least 15 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm I (CD19 positive chimeric antigen receptor T-cells) | Experimental | Drug: Cyclophosphamide, Drug: Fludarabine Phosphate, Other: Laboratory Biomarker Analysis, Biological: TisagenlecleucelLYMPHODEPLETING CHEMOTHERAPY: Patients may receive standard chemotherapy comprised of fludarabine phosphate IV over 1 hour and cyclophosphamide IV over 3 hours on days -5 to -3 or cyclophosphamide IV every 12 hours on days -5 to -3 at the discretion of the treating physician. Within 30 days post completion of lymphodepletion, patients receive CD19 positive chimeric antigen receptor T-cells IV over 15-30 minutes on day 0, or split into two portions on days 0 and 1. |
Who may qualify
- Ages
- 1 year to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with a history of CD19+ lymphoid malignancy defined as acute lymphoblastic leukemia, acute biphenotypic leukemia, non-Hodgkin's lymphoma, small lymphocytic lymphoma, or chronic lymphocytic leukemia with active disease defined by presence of > 5% malignant blasts in bone marrow and/or peripheral blood, and/or minimal residual disease by flow cytometry or molecular analysis for fusion proteins, and/or positive imaging for extramedullary disease; patients must have measurable disease at time of study treatment
- Confirmed history of CD19 positivity by flow cytometry for malignant cells
- Lansky/Karnofsky performance scale > 60%
- Patient able to provide written informed consent; parent or guardian of minor patient able to provide written informed consent
- Patient able to provide written informed consent for the long-term follow-up gene therapy study: 2006-0676; parent or guardian of minor patient able to provide written informed consent for the long-term follow-up gene therapy study: 2006-0676
Key exclusion criteria (6 listed)
- Positive beta human chorionic gonadotropin (HCG) in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization or lactating females
- Patients with known allergy to bovine or murine products
- Positive serology for human immunodeficiency virus (HIV)
- Active hepatitis B or active hepatitis C
- Has received donor lymphocyte infusion (DLI) product within 6 weeks of CAR T cell infusion
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 |
|---|---|---|
| CyclophosphamideAlso: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, CiclofosfamidaGiven IV | Drug | Arm I (CD19 positive chimeric antigen receptor T-cells) |
| Fludarabine PhosphateAlso: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, FludaraGiven IV | Drug | Arm I (CD19 positive chimeric antigen receptor T-cells) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm I (CD19 positive chimeric antigen receptor T-cells) |
| TisagenlecleucelAlso: CART-19, CART19, CTL019, CTL019 T-cellsGiven IV | Biological | Arm I (CD19 positive chimeric antigen receptor T-cells) |
Primary outcome
Maximum tolerated dose of genetically modified, CD19-specified T cells
Time frame: Up to 30 days
Will be defined as the highest dose for which the posterior probability of toxicity is closest to 25%. Demographic and clinical characteristics will be summarized using descriptive statistics by dose level. The number of patients with dose limiting toxicities will be reported at each dose level.
2 secondary outcomes
The proportion of patients for which a T cell product could not be prepared
Time frame: Up to 1 year
Proportion of patients experiencing response (complete response and partial response)
Time frame: Up to 1 year
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 30 Jun 2022.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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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.
Partow Kebriaei principal investigator
M.D. Anderson Cancer Center
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 Cyclophosphamide, Fludarabine Phosphate and Laboratory Biomarker Analysis in people with Acute Biphenotypic Leukemia and Acute Lymphoblastic Leukemia, run by M.D. Anderson Cancer Center 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 5 inclusion and 6 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 30 Jun 2022. 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?
Maximum tolerated dose of genetically modified, CD19-specified T cells (time frame: Up to 30 days). 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 30 Jun 2022.