CD19 PositivePhase 1/2NCT04029038
Modified Immune Cells (CD19-CD22 CAR T Cells) in Treating Patients With Recurrent or Refractory CD19 Positive, CD22 Positive Leukemia or Lymphoma
A Phase 1/2 study testing Autologous CD19/CD22 Chimeric Antigen Receptor T-cells, Cyclophosphamide and Fludarabine in people with CD19 Positive and CD22 Positive, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase I/II trial studies the side effects and best dose of modified immune cells called CD19-CD22 chimeric antigen receptor (CAR) T cells in treating patients with CD19 positive(+), CD22+ B-acute lymphoblastic leukemia, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma that has come back (recurrent) or does… Read more about this study
- Who is it for?
- Ages 6 months to 70 years
- Conditions the study is for
- CD19 Positive, CD22 Positive, Minimal Residual Disease
- What is being tested?
- Autologous CD19/CD22 Chimeric Antigen Receptor T-cells, Cyclophosphamide and Fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 15 May 2019to 16 Nov 2022
- Phase
- Phase 1/2
- 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 6 months to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with relapsed/refractory B-acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), or non-Hodgkin's lymphoma (NHL) treated with at least two lines of therapy, and have persistent or progressed disease including positive minimal residual disease (MRD)
- Patients may have received last cytotoxic chemotherapy at least 3 weeks prior to lymphodepleting chemotherapy
- Patient may continue targeted therapy until 2 weeks before initiation of lymphodepleting chemotherapy with the exception of ibrutinib
- Disease must be CD19 and/or CD22 positive by flow cytometry or immunohistochemistry
- Karnofsky/Lansky performance scale > 70
- Total bilirubin less than < 1.5 mg/dL except patients with Gilbert syndrome whose total bilirubin must be < 3.0mg/dL
Show all 23Show fewer
- Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT]) =< 2.5 X upper limit of normal (ULN)
- Alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 5.0 ULN
- Serum creatinine (as estimated by Cockcroft Gault) >= 60 cc/min
- Cardiac ejection fraction >= 50% without evidence of pericardiac effusion as determined by echocardiogram (ECHO) or multigated acquisition scan (MUGA), no clinical significant electrocardiogram (ECG) findings
- No clinical significant pleural effusion and baseline oxygen saturation >= 92%
- Absolute lymphocyte count >= 100/ul
- Be able to sign informed consent
- All participants who are able to have children must practice effective birth control while on study. Acceptable forms of birth control for female patients include: birth control pills, patches, or injections, intrauterine device (IUD), diaphragm with spermicide, or condom with spermicide. Acceptable forms of birth control for male patients include condom with spermicide. If female participant becomes pregnant during the study, she will be taken off this study. If male participant fathers a child while on study, he must immediately notify his doctor
- For patients with history of allogenic stem cell transplantation
- Should not have active acute graft-versus-host disease (GVHD) grade >= 2
- Should not be on immunosuppressants such as tacrolimus, sirolimus, cyclosporine, mycophenolates for a minimum of a month from CD19-CD22 CAR T cell infusion
- Should not be on more than physiologic dose of systemic steroid for adrenal insufficiency (prednisone equivalent 5mg/day)
- Transplantation should be more than 2 months from CD19-CD22 CAR T cell infusion
- Other cell therapy including CAR T cells, donor lymphocyte infusion, virus specific T cells, natural killer (NK) cells, etc should have 6 weeks of wash-out period from the CD19-CD22 CAR T cell infusion
- For patients with history of central nervous system (CNS) disease, CNS disease must be treated prior to enrollment
- For patients with prior treatment history of cell therapy such as other CAR T cells or CAR NK cells or NK cells, cell therapy should have a 6 weeks of wash-out period from CD19-CD22 CAR T cell infusion
- Be able to consent long-term follow-up protocol PA17-0483
Who cannot join
- Positive beta-human chorionic gonadotropin (hCG) in female of child bearing potential defined as not postmenopausal for 24 months or no previous surgical sterilization or lactating females
- Known positive serology for human immunodeficiency virus (HIV)
- Presence of active grade 3 or greater toxicity from the previous treatment
- Presence of active fungal, bacterial, viral, or other infection requiring IV antibiotics for management
- Presence of active neurologic disorders
- Concomitant use of other investigational agents
- Current use of corticosteroid more than physiological dose for adrenal insufficiency (prednisone equivalent at a dose higher than 10 mg/day)
- Presence of active CNS disease
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I/II Study of Dual CD19-CD22 Chimeric Antigen Receptor (CAR) T Cells in Patients With Advanced CD19+ CD22+ Lymphoid Malignancies
This phase I/II trial studies the side effects and best dose of modified immune cells called CD19-CD22 chimeric antigen receptor (CAR) T cells in treating patients with CD19 positive(+), CD22+ B-acute lymphoblastic leukemia, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma that has come back (recurrent) or does not respond to treatment (refractory). T-cells are collected from the patient and genetic materials called "chimeric antigen receptors (CAR)" are transferred to the collected T-cells. The CAR T-cells are then infused back to the patient's body. Giving CD19- CD22 CAR T cells after chemotherapy may help to control the disease.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the safety of infusion with chimeric antigen receptor T cells targeting CD19 and CD22.
II. To find the recommended phase II dose for recurrent/refractory CD19+CD22+ B cell malignancies.
SECONDARY OBJECTIVES:
- To describe the overall response rate and complete response rate of relapsed B cell malignancies treated with CAR-T cells targeting CD19 and CD22.
II. To assess other response variables including minimal residual disease (MRD) negative remission, overall survival (OS), and event free survival (EFS).
EXPLORATORY OBJECTIVES:
- To evaluate the immune reconstitution and persistence of CAR T cells for one year post infusion.
OUTLINE: This is a phase I, dose escalation study of autologous CD19/CD22 chimeric antigen receptor T-cells (CD19-CD22 CAR T cells) followed by a phase II study.
Patients receive standard of care cyclophosphamide intravenously (IV) over 30 minutes and fludarabine IV over 30 minutes on days -5, -4, and -3, and then receive CD19-CD22 CAR T cells IV on day 0. Patients with relapsed or persistent disease after a protocol assessment may receive a second infusion of CD19-CD22 CAR T cells.
After completion of study treatment, patients are followed up at 1, 2, 3, 6, and 12 months.
- Conditions
- CD19 Positive, CD22 Positive, Minimal Residual Disease, Progressive Disease, Recurrent B Acute Lymphoblastic Leukemia, Recurrent Chronic Lymphocytic Leukemia
- Being tested
- Autologous CD19/CD22 Chimeric Antigen Receptor T-cells, Cyclophosphamide, Fludarabine
- Medical subject headings
- Neoplasm, Residual, Disease Progression, Burkitt Lymphoma, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous CD19/CD22 Chimeric Antigen Receptor T-cellsBiological
Also called Autologous Anti-CD19/CD22 CAR-T Cells, Autologous CD19/CD22 CAR T Cells, Autologous CD19/CD22 CAR T-cells, Autologous CD19/CD22 Chimeric Antigen Receptor T Cells
Given IV
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida
Given IV
FludarabineDrug
Also called Fluradosa
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (CD19-CD22 CAR T cells) | Experimental | Patients receive standard of care cyclophosphamide IV over 30 minutes and fludarabine IV over 30 minutes on days -5, -4, and -3, and then receive CD19-CD22 CAR T cells IV on day 0. Patients with relapsed or persistent disease after a protocol assessment may receive a second infusion of CD19-CD22 CAR T cells. Receives: Biological: Autologous CD19/CD22 Chimeric Antigen Receptor T-cells; Drug: Cyclophosphamide; Drug: Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Optimal chimeric antigen receptor (CAR) T cell dose level
Dose-finding will be done using the sequentially adaptive phase I-II EffTox method.
Measured: Up to 30 days
Incidence of adverse events (adverse events)
Toxicity is defined as a grade 3, 4, or 5 cytokine release syndrome, neurotoxicity, or National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 with onset within 30 days of cell infusion. Adverse events that are considered disease-related (not suspected of relationship to CD19-CD22 -CAR T cells) will not be considered dose-limiting toxicities. Only those AEs that occur during the first 30 days after infusion, which are suspected to be related to conditioning lymphodepletion chemotherapy regimen and/or CD19 -CD22-CAR T cells (any component of the treatment regimen), and meet the following criteria, will be used in the definition of toxicity. Hematologic toxicities will not be considered in the definition of toxicity, as pancytopenia is a common toxicity with this regimen.
Measured: Up to 30 days
Efficacy in complete response (CR) or partial response
Efficacy is defined as the patient being alive and in complete response (CR) or partial response (PR) at day 30 post cell infusion.
Measured: Day 30 post cell infusion
Secondary outcomes (2)
Progression-free survival
Unadjusted distributions of the time-to-event outcomes will be estimated using the method of Kaplan and Meier and their relationship to prognostic covariates and T-cell dose level will be evaluated by Bayesian piecewise exponential survival regression.
Measured: Up to 1 year post T-cell infusion
Overall survival
Unadjusted distributions of the time-to-event outcomes will be estimated using the method of Kaplan and Meier and their relationship to prognostic covariates and T-cell dose level will be evaluated by Bayesian piecewise exponential survival regression.
Measured: Up to 1 year post T-cell infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2019
- Study start15 May 2019
- Primary completion16 Nov 2022
- Study completion16 Nov 2022
Why it stopped: 0 participant accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CD19 PositiveStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Jin S Im, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04029038
- Sponsor's protocol ID
- 2019-0042
- Other IDs
- NCI-2019-04229, 2019-0042, P30CA016672
- Status last verified
- Aug 2023
- First submitted
- 19 Jul 2019
- Last updated
- 21 Aug 2023
- 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 21 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Dual CD19-CD22 Chimeric Antigen Receptor (CAR) T Cells in Patients With Advanced CD19+ CD22+ Lymphoid Malignancies
- ClinicalTrials.gov ID
- NCT04029038
- Acronym / sponsor ID
- 2019-0042
- Conditions
- CD19 Positive, CD22 Positive, Minimal Residual Disease, Progressive Disease, Recurrent B Acute Lymphoblastic Leukemia, Recurrent Chronic Lymphocytic Leukemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: 0 participant accrual
- Enrolment
- 0 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 15 May 2019 (actual)
- Primary completion
- 16 Nov 2022 (actual)
- Study completion
- 16 Nov 2022 (actual)
- First posted
- 23 Jul 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.
This phase I/II trial studies the side effects and best dose of modified immune cells called CD19-CD22 chimeric antigen receptor (CAR) T cells in treating patients with CD19 positive(+), CD22+ B-acute lymphoblastic leukemia, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma that has come back (recurrent) or does not respond to treatment (refractory). T-cells are collected from the patient and genetic materials called "chimeric antigen receptors (CAR)" are transferred to the collected T-cells. The CAR T-cells are then infused back to the patient's body. Giving CD19- CD22 CAR T cells after chemotherapy may help to control the disease.
Detailed description
PRIMARY OBJECTIVES:
- To determine the safety of infusion with chimeric antigen receptor T cells targeting CD19 and CD22.
II. To find the recommended phase II dose for recurrent/refractory CD19+CD22+ B cell malignancies.
SECONDARY OBJECTIVES:
- To describe the overall response rate and complete response rate of relapsed B cell malignancies treated with CAR-T cells targeting CD19 and CD22.
II. To assess other response variables including minimal residual disease (MRD) negative remission, overall survival (OS), and event free survival (EFS).
EXPLORATORY OBJECTIVES:
- To evaluate the immune reconstitution and persistence of CAR T cells for one year post infusion.
OUTLINE: This is a phase I, dose escalation study of autologous CD19/CD22 chimeric antigen receptor T-cells (CD19-CD22 CAR T cells) followed by a phase II study.
Patients receive standard of care cyclophosphamide intravenously (IV) over 30 minutes and fludarabine IV over 30 minutes on days -5, -4, and -3, and then receive CD19-CD22 CAR T cells IV on day 0. Patients with relapsed or persistent disease after a protocol assessment may receive a second infusion of CD19-CD22 CAR T cells.
After completion of study treatment, patients are followed up at 1, 2, 3, 6, and 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (CD19-CD22 CAR T cells) | Experimental | Biological: Autologous CD19/CD22 Chimeric Antigen Receptor T-cells, Drug: Cyclophosphamide, Drug: FludarabinePatients receive standard of care cyclophosphamide IV over 30 minutes and fludarabine IV over 30 minutes on days -5, -4, and -3, and then receive CD19-CD22 CAR T cells IV on day 0. Patients with relapsed or persistent disease after a protocol assessment may receive a second infusion of CD19-CD22 CAR T cells. |
Who may qualify
- Ages
- 6 months to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (23 listed)
- Patients with relapsed/refractory B-acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), or non-Hodgkin's lymphoma (NHL) treated with at least two lines of therapy, and have persistent or progressed disease including positive minimal residual disease (MRD)
- Patients may have received last cytotoxic chemotherapy at least 3 weeks prior to lymphodepleting chemotherapy
- Patient may continue targeted therapy until 2 weeks before initiation of lymphodepleting chemotherapy with the exception of ibrutinib
- Disease must be CD19 and/or CD22 positive by flow cytometry or immunohistochemistry
- Karnofsky/Lansky performance scale > 70
Key exclusion criteria (8 listed)
- Positive beta-human chorionic gonadotropin (hCG) in female of child bearing potential defined as not postmenopausal for 24 months or no previous surgical sterilization or lactating females
- Known positive serology for human immunodeficiency virus (HIV)
- Presence of active grade 3 or greater toxicity from the previous treatment
- Presence of active fungal, bacterial, viral, or other infection requiring IV antibiotics for management
- Presence of active neurologic disorders
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 |
|---|---|---|
| Autologous CD19/CD22 Chimeric Antigen Receptor T-cellsAlso: Autologous Anti-CD19/CD22 CAR-T Cells, Autologous CD19/CD22 CAR T Cells, Autologous CD19/CD22 CAR T-cells, Autologous CD19/CD22 Chimeric Antigen Receptor T CellsGiven IV | Biological | Treatment (CD19-CD22 CAR T cells) |
| CyclophosphamideAlso: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, CiclofosfamidaGiven IV | Drug | Treatment (CD19-CD22 CAR T cells) |
| FludarabineAlso: FluradosaGiven IV | Drug | Treatment (CD19-CD22 CAR T cells) |
Primary outcome
Optimal chimeric antigen receptor (CAR) T cell dose level
Time frame: Up to 30 days
Dose-finding will be done using the sequentially adaptive phase I-II EffTox method.
Incidence of adverse events (adverse events)
Time frame: Up to 30 days
Toxicity is defined as a grade 3, 4, or 5 cytokine release syndrome, neurotoxicity, or National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 with onset within 30 days of cell infusion. Adverse events that are considered disease-related (not suspected of relationship to CD19-CD22 -CAR T cells) will not be considered dose-limiting toxicities. Only those AEs that occur during the first 30 days after infusion, which are suspected to be related to conditioning lymphodepletion chemotherapy regimen and/or CD19 -CD22-CAR T cells (any component of the treatment regimen), and meet the following criteria, will be used in the definition of toxicity. Hematologic toxicities will not be considered in the definition of toxicity, as pancytopenia is a common toxicity with this regimen.
Efficacy in complete response (CR) or partial response
Time frame: Day 30 post cell infusion
Efficacy is defined as the patient being alive and in complete response (CR) or partial response (PR) at day 30 post cell infusion.
2 secondary outcomes
Progression-free survival
Time frame: Up to 1 year post T-cell infusion
Overall survival
Time frame: Up to 1 year post T-cell infusion
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2023.
- 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.
Jin S Im 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 1/2 study testing Autologous CD19/CD22 Chimeric Antigen Receptor T-cells, Cyclophosphamide and Fludarabine in people with CD19 Positive and CD22 Positive, 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 23 inclusion and 8 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: withdrawn, as of the sponsor's last update on 21 Aug 2023. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was withdrawn before enrolling participants, so there are no results.
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?
Optimal chimeric antigen receptor (CAR) T cell dose level (time frame: Up to 30 days). The study lists 3 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 21 Aug 2023.