Acute Lymphoblastic LeukemiaPhase 1/2ISIKOK-19NCT04206943
Study of CD19 Specific Chimeric Antigen Receptor Positive T Cells (CAR-T) in ALL and NHL
A Phase 1/2 study testing Car-T Cell Therapy in people with Acute Lymphoblastic Leukemia and Non Hodgkin Lymphoma, run by Acibadem University at 1 site in Turkey (Türkiye).
Trial summary
It is a treatment that activates and strengthens the immune system against cancer. Recently, T cell receptors have been genetically rearranged by adaptive T cell therapies, which are promising in the fight against cancer, and are now able to recognize antigens on tumor cells. Read more about this study
- Who is it for?
- Ages 3 to 65 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia, Non Hodgkin Lymphoma
- What is being tested?
- Car-T Cell Therapy
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 12 Oct 2019to 1 Jan 2021
- 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 3 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Been diagnosed with CD19 (+) B-Acute lymphoblastic lymphoma or CD19 (+) Non-Hodgkin Lymphoma
- Having a measurable disease
- Relapsed/ refractory (at least 2 cases to the ward; in relapse after autologous transplantation in NHL) disease
- CD19 (+) expression in tumor cells by bone marrow/tissue or peripheral blood flow cytometry for relapse patients in the 3-month before the study period
- Bone marrow relapse after allogenic stem cell transplantation and at least 6 months between CAR-T (ISIKOK-19 ©) cell infusion and stem cell transplantation
- Philadelphia gene + B-ALL patient should have received second line treatment with tyrosine kinase inhibitor (TKI) or the usage of tyrosine kinase inhibitor (TKI) for the patient is contraindicated
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- Patient; lack of appropriate donor, complications due to previous stem cell transplantation, or rejection of stem cell transplantation as a treatment option after consultation with a physician, or lack of allogenic stem cell transplantation due to high tumor burden.
- Lack of organ dysfunction:
- Maximum serum creatinine value: 1.7 mg / decilitre (male patients), 1.4 mg / decilitre (female patients)
- Liver function tests are within normal limits
- Bilirubin <2.0 mg / decilitre
- Central oxygen pressure in room air > 91% and no dyspnea
- Measurement of left ventricular ejection fraction ≥45% and left ventricular systolic function ≥28% by echocardiography during screening
- Expected survival is ≥ 3 months
- Performance condition: Karnofsky ≥ 50%
- Consent to oral contraceptives
- Approve treatment
Who cannot join
- Concomitant history of cardiac, hepatic, neurologic, nephrologic, psychiatric, autoimmune and additional oncological diseases affecting physiological functions
- Life expectancy <2 months
- Hepatitis B, Hepatitis C, Human immunodeficiency virus infection
- Before CAR-T (ISIKOK-19 ©) cell infusion
- Systemic steroid treatments, tyrosine kinase inhibitors, hydroxyurea, short-acting cytotoxic drugs should be stopped 72 hours before.
- 1 week ago, vincristine, 6-mercaptopurine, 6-thioguanine, methotrexate (if <25 mg / m^2), cytosine arabinoside (if <100 mg / m^2), asparaginase and intrathecal treatments should be stopped.
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- 2 weeks ago, salvage treatments (chemotherapy drugs other than lymphodepletion as part of the protocol, clofarabine, cytosine arabinoside (if> 100 mg / m^2), anthracyclines, methotrexate (if ≥25 mg / m^2), drugs used for graft versus host disease, long-acting growth factors, vincristine, immunomodulatory drugs should be stopped.
- Radiotherapy taken outside the central nervous system should be stopped 2 weeks prior.
- Any systemic treatment with pegylated asparaginase and donor lymphocyte infusion should be stopped 4 weeks prior.
- Anti-t cell therapies containing T cell lysis or toxic antibodies should be stopped 8 weeks before.
- Radiotherapy for the central nervous system should be stopped 8 weeks ago.
- Less than 3 months after stem cell transplantation
- Below 60% in tissue biopsies and / or CD19 expression in tumor cells by flow cytometric analysis in bone marrow is below 85%
- Allergic to drugs that are used at any stage of treatment
- Having received experimental drug treatment in the last month
- Previously entered a cellular therapy and / or a gene therapy program
- Disapproval of the storage of tissues and cells
- Isolated disease that occurs outside the bone
- A genetic disease associated with concomitant bone marrow failure
- Active Grade 2-4 acute or diffuse chronic graft versus host disease
- Being pregnant or breastfeeding
- Disapproval the treatment
- Patients with slow CAR-T cell expansion (the cell number is not doubled in 48 hours) and with less than 10% expression of CAR-T cells during production, < 60% cytotoxicity results in in-vitro study (i.e, patients whose product is inappropriate)
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site, 1 recruiting
- Recruiting
Acıbadem Labcell Cellular Therapy Laboratories
Istanbul, 34758
Ercument Ovalı, +905325729174, ercument.ovali@acibademlabcell.com.tr
About this study
Official title: Phase I/ II Study of Cluster of Differentiation 19 (CD19) Specific CAR-T Cells (ISIKOK 19) in Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) and Non Hodgkin Lymphoma (NHL)
It is a treatment that activates and strengthens the immune system against cancer. Recently, T cell receptors have been genetically rearranged by adaptive T cell therapies, which are promising in the fight against cancer, and are now able to recognize antigens on tumor cells. These modified T cell receptors are called chimeric antigen receptors. Many previous clinical studies have shown that different CAR-T cells are effective in relapse / refractory B cell cancers and NHL.
Read the detailed description
Clinical trials of CAR-T cell therapy started at the end of 1990s. Phase I and II trials have still evaluated the efficacy and safety of CAR-T cells in hematological and solid cancers. The therapy involves drawing blood from patients and isolation of the T cells. Next, the T cells are genetically engineered in a laboratory by using virus or sleeping beauty to produce receptors on their surface named as chimeric antigen receptors. As the last step, the CAR-T cells are infused back into the patient. After infusion, it is expected that the CAR-T cells further increase in number in the patient's body and with the help of their engineered receptor to recognize and target the antigen on the surface of the cancerous cells for antitumor effect.
- Conditions
- Acute Lymphoblastic Leukemia, Non Hodgkin Lymphoma
- Being tested
- Car-T Cell Therapy
- Keywords
- CAR-T Cell, CD19, ALL, NHL, Cancer, Chimeric Antigen Receptor
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Non-Hodgkin, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Car-T Cell TherapyBiological
Lymphodepletion Protocol:
- -6. Day: Cyclophosphamide 300 mg / m^2 i.v.
- -5. -4. and -3. Days: Fludarabine 30 mg / m^2 i.v. In addition, one day before the lymphodepletion protocol, xanthine oxidase enzyme inhibitor tablets received 100 mg / day p.o. and 0.9% sodium chloride solution 2000 ml / day i.v. infusion on protocol day received and continues for 2 weeks
Car-T cells are administered in 3 split doses. Day 0: 20% or 40% (20% in patients with high tumor burden - in patients with bulky disease and / or more than 15% blast in bone marrow, 40% in patients with low tumor burden) Day 2: 30% or 50%, (the total amount of Car-T cell dose that should be given in the first 2 days should be 70%.) Third dose (%30);is given on the 7th day in the absence of cytokine release syndrome, or if cytokine release syndrome occurs, Car-T cells are given within 1 month if the number of copies falls below 5,000 / ml in 2 consecutive measurements.
| Study group | Role | What they receive |
|---|---|---|
| A Low Dose | Experimental | 4 x 10^6 Car-T cell/ kg Receives: Biological: Car-T Cell Therapy |
| B High Dose | Experimental | 6 x 10^6 Car-T cell/ kg Receives: Biological: Car-T Cell Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events
Type, frequency and severity of adverse events (AEs) and laboratory abnormalities.
Measured: 6 Months
Secondary outcomes (15)
Complete Remission Rate
It is determined by the evaluation of complete remission (CR) obtained in the first 3 months.
Measured: 3 Months
Total Response Rate
CR obtained in the first 3 months is determined by evaluation of partial remission, incomplete partial remission and stable disease responses.
Measured: 3 Months
Duration of Remission (DOR)
Duration of remission (DOR) is defined as the duration from the date when the response criteria of CR or CRi is first met to the date of relapse or death due to underlying cancer, whichever occurs first.
Measured: 6 Months
Relapse Free Survival (RFS)
Relapse free survival (RFS) is measured by the time from achievement of CR or CRi whatever occurs first to relapse or death due to any cause during CR or CRi.
Measured: 6 Months
Progression Free Survival
Only in the NHL is the duration from CAR T cell infusion to progression
Measured: 6 Months
Event-Free Survival (EFS)
Event free survival (EFS) is the time from date of first Car-T cell infusion to the earliest of the following:
- Death from any cause
- Relapse
Measured: 6 Months
Overall Survival
Overall survival (OS) is the time from date of first Car-T Cell infusion to the date of death due to any reason.
Measured: 6 Months
Duration to maximum response
The duration from date of the first Car-T cell infusion to complete remission in ALL.
The duration from date of the first Car-T cell infusion to complete remission and partial remission in NHL
Measured: 6 Months
The impact of baseline tumor burden on response
Best overall response will be summarized by baseline tumor burden (MRD, extramedullary disease, etc.)
Measured: 6 Months
The relationship between CRS/CRES efficiency
The relationship between CRS / CRES grades and total response rates are determined by correlation between DOR, RFS, EFS, PFS, OS.
Measured: 6 Months
The relationship between the total response and Car-T Cell persistence
The relationship between total response and the number of Car-T copies is determined by the correlation between DOR, RFS, EFS, PFS, OS
Measured: 6 Months
The relationship between Car-T Cell product content and responses
The relationship between Car-T Cell subgroups and total response are determined by the correlation between DOR, RFS, EFS, PFS, OS.
Measured: 6 Months
Car-T cell proliferation capability
The relationship between the Car-T Cell proliferation capability and the total response, are determined by the correlation between DOR, RFS, EFS, PFS, OS.
Measured: 6 months
The relationship between MRD grade and clinical response
The relationship between MRD grade and total response are determined by correlation between DOR, RFS, EFS, PFS, OS.
Measured: 6 Months
The relationship between the incidence of immune response to Car-T cells and the persistence of Car-T cell
It is assessed as the relationship between antiserum effectivity against Car-T cells and Car-T cell copy number in blood.
Measured: 6 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2019
- Study start12 Oct 2019
- Primary completion1 Jan 2021 (estimated)
- Study completion1 Jan 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by Acibadem UniversityThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Acibadem University
- Sponsor type
- University, hospital or other
- Collaborators
- Acıbadem Atunizade Hospital, The Scientific and Technological Research Council of Turkey, Acıbadem Labcell
- Responsible party
- Sponsor
- Investigators
- Ercument Ovali, MD, Study director, Director
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04206943
- Sponsor's protocol ID
- CD19-SP-CAR-T
- Acronym
- ISIKOK-19
- Status last verified
- Sep 2019
- First submitted
- 16 Dec 2019
- Last updated
- 27 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/ II Study of Cluster of Differentiation 19 (CD19) Specific CAR-T Cells (ISIKOK 19) in Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) and Non Hodgkin Lymphoma (NHL)
- ClinicalTrials.gov ID
- NCT04206943
- Acronym / sponsor ID
- ISIKOK-19 / CD19-SP-CAR-T
- Conditions
- Acute Lymphoblastic Leukemia, Non Hodgkin Lymphoma
- Keywords
- CAR-T Cell, CD19, ALL, NHL, Cancer, Chimeric Antigen Receptor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Acibadem UniversityUniversity, hospital or other
- Collaborators
- Acıbadem Atunizade Hospital, The Scientific and Technological Research Council of Turkey, Acıbadem Labcell
- Study start
- 12 Oct 2019 (actual)
- Primary completion
- 1 Jan 2021 (estimated)
- Study completion
- 1 Jan 2021 (estimated)
- First posted
- 20 Dec 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.
It is a treatment that activates and strengthens the immune system against cancer. Recently, T cell receptors have been genetically rearranged by adaptive T cell therapies, which are promising in the fight against cancer, and are now able to recognize antigens on tumor cells. These modified T cell receptors are called chimeric antigen receptors. Many previous clinical studies have shown that different CAR-T cells are effective in relapse / refractory B cell cancers and NHL.
Detailed description
Clinical trials of CAR-T cell therapy started at the end of 1990s. Phase I and II trials have still evaluated the efficacy and safety of CAR-T cells in hematological and solid cancers. The therapy involves drawing blood from patients and isolation of the T cells. Next, the T cells are genetically engineered in a laboratory by using virus or sleeping beauty to produce receptors on their surface named as chimeric antigen receptors. As the last step, the CAR-T cells are infused back into the patient. After infusion, it is expected that the CAR-T cells further increase in number in the patient's body and with the help of their engineered receptor to recognize and target the antigen on the surface of the cancerous cells for antitumor effect.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A Low Dose | Experimental | Biological: Car-T Cell Therapy4 x 10^6 Car-T cell/ kg |
| B High Dose | Experimental | Biological: Car-T Cell Therapy6 x 10^6 Car-T cell/ kg |
Who may qualify
- Ages
- 3 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (17 listed)
- Been diagnosed with CD19 (+) B-Acute lymphoblastic lymphoma or CD19 (+) Non-Hodgkin Lymphoma
- Having a measurable disease
- Relapsed/ refractory (at least 2 cases to the ward; in relapse after autologous transplantation in NHL) disease
- CD19 (+) expression in tumor cells by bone marrow/tissue or peripheral blood flow cytometry for relapse patients in the 3-month before the study period
- Bone marrow relapse after allogenic stem cell transplantation and at least 6 months between CAR-T (ISIKOK-19 ©) cell infusion and stem cell transplantation
Key exclusion criteria (23 listed)
- Concomitant history of cardiac, hepatic, neurologic, nephrologic, psychiatric, autoimmune and additional oncological diseases affecting physiological functions
- Life expectancy <2 months
- Hepatitis B, Hepatitis C, Human immunodeficiency virus infection
- Before CAR-T (ISIKOK-19 ©) cell infusion
- Allergic to drugs that are used at any stage of treatment
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 |
|---|---|---|
| Car-T Cell TherapyLymphodepletion Protocol: * -6. Day: Cyclophosphamide 300 mg / m^2 i.v. * -5. -4. and -3. Days: Fludarabine 30 mg / m^2 i.v. In addition, one day before the lymphodepletion protocol, xanthine oxidase enzyme inhibitor tablets received 100 mg / day p.o. and 0.9% sodium chloride solution 2000 ml / day i.v. infusion on protocol day received and continues for 2 weeks Car-T cells are administered in 3 split doses. Day 0: 20% or 40% (20% in patients with high tumor burden - in patients with bulky disease and / or more than 15% blast in bone marrow, 40% in patients with low tumor burden) Day 2: 30% or 50%, (the total amount of Car-T cell dose that should be given in the first 2 days should be 70%.) Third dose (%30);is given on the 7th day in the absence of cytokine release syndrome, or if cytokine release syndrome occurs, Car-T cells are given within 1 month if the number of copies falls below 5,000 / ml in 2 consecutive measurements. | Biological | A Low Dose, B High Dose |
Primary outcome
Incidence of Adverse Events
Time frame: 6 Months
Type, frequency and severity of adverse events (AEs) and laboratory abnormalities.
15 secondary outcomes
Complete Remission Rate
Time frame: 3 Months
Total Response Rate
Time frame: 3 Months
Duration of Remission (DOR)
Time frame: 6 Months
Relapse Free Survival (RFS)
Time frame: 6 Months
Progression Free Survival
Time frame: 6 Months
Event-Free Survival (EFS)
Time frame: 6 Months
Overall Survival
Time frame: 6 Months
Duration to maximum response
Time frame: 6 Months
The impact of baseline tumor burden on response
Time frame: 6 Months
The relationship between CRS/CRES efficiency
Time frame: 6 Months
The relationship between the total response and Car-T Cell persistence
Time frame: 6 Months
The relationship between Car-T Cell product content and responses
Time frame: 6 Months
Car-T cell proliferation capability
Time frame: 6 months
The relationship between MRD grade and clinical response
Time frame: 6 Months
The relationship between the incidence of immune response to Car-T cells and the persistence of Car-T cell
Time frame: 6 Months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2020.
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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.
Ercument Ovali, MD study director
Director
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 Car-T Cell Therapy in people with Acute Lymphoblastic Leukemia and Non Hodgkin Lymphoma, run by Acibadem University at 1 site in Turkey (Türkiye).
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 17 inclusion and 23 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: status not confirmed, as of the sponsor's last update on 27 Jan 2020. 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 Turkey (Türkiye). 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ercument Ovalı, MD (+905325729174, ercument.ovali@acibadem.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Adverse Events (time frame: 6 Months). 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 27 Jan 2020.