Relapsed Acute Lymphoblastic Leukemia (ALL)Early Phase 1PAKCAR-ALLNCT07695012
CAR-T Cell Therapy for ALL
A Early Phase 1 study testing CAR-T cell infusion in people with Relapsed Acute Lymphoblastic Leukemia (ALL), run by Dr. Zaineb Akram at 1 site in Pakistan.
Trial summary
Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and the second most frequent acute leukemia in adults. B-cell ALL constitutes approximately 85% of all ALL diagnoses. Read more about this study
- Who is it for?
- Ages 5 to 50 years
- Conditions the study is for
- Relapsed Acute Lymphoblastic Leukemia (ALL)
- What is being tested?
- CAR-T cell infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 sitePakistan
- Study dates
- 1 Jun 2026to 31 Dec 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
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 5 to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- All of the following criteria must be met for enrolment:
- 1. Age ≥5 years and ≤50 years at the time of consent
- 2. Morphologically or immunophenotypically confirmed B-cell ALL (CD19+) meeting one or more of the following relapsed/refractory criteria:
- a. Second or subsequent bone marrow relapse (BM ≥2nd relapse)
- b. Any BM relapse following prior allogeneic HSCT, provided ≥6 months have elapsed from SCT to planned CAR-T infusion
- c. Primary refractory disease: failure to achieve CR after ≥2 cycles of standard induction chemotherapy; or chemorefractory: failure to achieve CR after ≥1 cycle of standard salvage chemotherapy for relapsed ALL
Show all 44Show fewer
- d. Philadelphia chromosome-positive (Ph+) ALL: intolerant to or failed ≥2 lines of TKI therapy, or TKI contraindicated
- e. Ineligibility for allo-HSCT due to: comorbid disease, lack of suitable donor, contraindication to conditioning, or patient refusal after documented discussion with a BMT physician not part of the study team
- 3. CD19 expression on tumour cells confirmed by multi-parameter flow cytometry within 3 months of enrolment (≥20% CD19-positive blasts required)
- 4. Bone marrow blast burden ≥5% by morphological assessment at screening
- 5. Adequate organ function at screening:
- a. Renal: Age-adjusted serum creatinine within normal limits per CTCAE paediatric reference tables, or GFR ≥30 mL/min/1.73m² (MDRD/CKD-EPI)
- b. Hepatic: ALT/AST ≤5× ULN; Total bilirubin <2.0 mg/dL
- c. Cardiac: LVEF ≥45% or LVSF ≥28% on echocardiogram (performed within 28 days of screening)
- d. Pulmonary: ≤Grade 1 dyspnoea; SpO₂ ≥91% on room air
- 6. ECOG performance status ≤2 (age ≥16 years); Lansky performance scale ≥50 (age <16 years)
- 7. Life expectancy >12 weeks in the opinion of the investigator
- 8. Adequate haematological status to tolerate leukapheresis (ALC ≥100/µL and CD3+ count ≥100/µL at time of apheresis, or acceptable stored product available)
- 9. Patients who have undergone prior allo-HSCT must have: (a) no active acute GVHD (Grade ≥2) or extensive chronic GVHD; (b) no systemic immunosuppression for GVHD within 4 weeks prior to CAR-T infusion
- 10. Written informed consent from patient (and parent/guardian if age <18 years); assent from patients aged 7-17 years
- 11. Willingness and ability to comply with study procedures, visit schedule, and long-term follow-up requirements including the 15-year gene therapy safety surveillance
- 12. Negative pregnancy test (serum or urine β-hCG) within 48 hours of CAR-T infusion for females of childbearing potential (defined as post-menarche and not surgically sterilised) 4.3 Exclusion Criteria
- Patients meeting ANY of the following criteria will be excluded:
- 1. Isolated extra-medullary (CNS-only or testicular-only) disease relapse without bone marrow involvement
- 2. Active CNS involvement by ALL, defined as CNS-3 status per NCCN criteria (CSF blasts on cytospin, cranial nerve palsy, or brain parenchymal disease) at time of screening. Patients with prior CNS disease that has been effectively treated and cleared are eligible
- 3. Burkitt's lymphoma/leukemia (mature B-ALL with sIg positive, FAB L3 morphology and/or MYC translocation)
- 4. T-cell ALL or ambiguous lineage leukemia
- 5. Known congenital bone marrow failure syndromes: Fanconi anaemia, Shwachman-Diamond syndrome, Kostmann syndrome, Diamond-Blackfan anaemia, or any other inherited aplastic anaemia. (Down syndrome patients are NOT excluded)
- 6. Prior treatment with any CAR-T or adoptive T-cell product
- 7. Prior anti-CD19 therapy of any kind (including blinatumomab) within 4 weeks of screening; or confirmed CD19-negative (antigen-loss) relapse on anti-CD19-based therapy. [Note: prior blinatumomab ≥4 weeks before screening is not exclusionary if CD19 positivity is confirmed at re-screening]
- 8. Prior gene therapy with a viral vector (non-CAR gene therapy); or prior receipt of a gene-edited cellular product
- 9. Active uncontrolled infection at screening (bacterial, fungal, viral or parasitic). Patients with controlled or treated infection may be enrolled at investigator discretion
- 10. Active Hepatitis B (HBsAg positive, or anti-HBc positive with detectable HBV DNA); active Hepatitis C (anti-HCV positive with detectable HCV RNA); or HIV positive (confirmed within 8 weeks of screening)
- 11. Active Grade 2-4 acute GVHD or active moderate/severe chronic GVHD
- 12. Prior malignancy other than B-ALL in the last 3 years (except carcinoma in situ of cervix or skin treated with curative intent, with no evidence of active disease)
- 13. Investigational medicinal product (IMP) exposure within 30 days prior to screening, or within 5 half-lives, whichever is longer
- 14. Pregnant or breastfeeding women
- 15. Uncontrolled psychiatric condition or severe cognitive impairment that would preclude informed consent or compliance with protocol procedures
- 16. Any medical condition that, in the opinion of the investigator, would place the patient at unacceptable risk from the study procedures
- 17. Prohibited concomitant medications at time of CAR-T infusion (detailed in Section 6.5):
- Systemic corticosteroids >physiologic replacement (>12 mg/m²/day hydrocortisone equivalent) within 72 hours prior to CAR-T infusion
- Anti-T-cell antibody therapy (ATG, alemtuzumab) within 8 weeks prior to CAR-T infusion
- Systemic GVHD immunosuppression within 4 weeks prior to CAR-T infusion
- Donor lymphocyte infusion within 6 weeks prior to CAR-T infusion
Who cannot join
- -
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Pakistan1 site, 1 recruiting
- Recruiting
National University of Medical Sciences, Clinical Trial Unit
Rawalpindi, 46000
Maryam Khan, MBBS,MRCP,FCPS(Cl Haem), +923366395758, maryam.khan9882@gmail.com
Nadia Sial, PhD, +923315582265, nadiaharif@gail.com
About this study
Official title: A Pilot, Single-Arm, Open-Label Feasibility Study of Autologous Anti-CD19 Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Pediatric and Young Adult Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia (r/r B-ALL)
Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and the second most frequent acute leukemia in adults. B-cell ALL constitutes approximately 85% of all ALL diagnoses. In Pakistan, ALL represents the most prevalent haematological malignancy presenting to tertiary centres, with AFBMTC receiving the largest national referral volume for haematological malignancies and transplantation.
First-line combination chemotherapy achieves complete remission (CR) in >95% of paediatric patients; however, 15-20% relapse. Outcomes following first relapse are substantially inferior: second-line salvage chemotherapy achieves CR2 in 30-50% of patients, and long-term event-free survival (EFS) after conventional chemotherapy alone is <10%. Outcomes in adult ALL are even more dismal, with OS at 5 years below 40% even in first CR without allogeneic transplant.
Patients with primary refractory ALL or multiply relapsed ALL have an unmet medical need for novel therapeutic approaches. The classical paradigm of chemotherapy followed by allogeneic haematopoietic stem cell transplantation (allo-HSCT) is limited by donor availability, conditioning-related mortality, and inability to achieve remission before transplant.
Read the detailed description
1.2 CD19 as a Therapeutic Target CD19 is a B-lineage surface glycoprotein expressed on the majority of B-cell ALL blasts, retained through disease evolution, and absent on haematopoietic stem cells, non-haematopoietic tissues, and most normal tissues. CD19 expression is confirmed in >95% of B-ALL cases, making it the optimal target for immunotherapy. The only significant on-target off-tumour consequence is B-cell aplasia and hypogammaglobulinaemia, which are clinically manageable with immunoglobulin replacement.
1.3 CAR-T Cell Therapy: Scientific and Clinical Rationale Chimeric antigen receptor T-cell (CAR-T) therapy involves ex vivo genetic modification of autologous T cells to express a synthetic receptor comprising: (1) an extracellular antigen-binding domain (anti-CD19 scFv), (2) a hinge and transmembrane domain, (3) an intracellular costimulatory domain (4-1BB/CD137), and (4) a CD3ζ signalling domain. Upon infusion, CAR-T cells recognise CD19+ target cells in an MHC-independent manner, inducing direct cytotoxicity, cytokine release, and in vivo proliferation.
The 4-1BB costimulatory domain (used in this protocol) confers superior persistence and memory formation compared to CD28-based constructs, as demonstrated in seminal studies from the University of Pennsylvania and subsequently confirmed in the ELIANA global Phase II trial of tisagenlecleucel (Maude et al., NEJM 2018), which demonstrated an overall remission rate of 81% and 12-month EFS of 50% in heavily pre-treated paediatric and young adult r/r B-ALL.
1.4 Institutional Rationale and LMIC Context AFBMTC is Pakistan's first and largest haematology and cellular therapy centre, established in 2001 under NUMS, with a cumulative experience of >2,000 allogeneic, autologous, and haploidentical HSCTs. AFBMTC possesses critical institutional infrastructure for CAR-T implementation including GMP-equivalent cleanroom facilities, validated cryopreservation and leukapheresis capabilities, and an established mesenchymal stromal cell (MSC) GMP program with over a decade of experience - directly translatable to CAR-T manufacturing quality standards.
Access to commercially approved CAR-T products (tisagenlecleucel, axicabtagene ciloleucel) is prohibitively expensive and effectively unavailable in Pakistan. AFBMTC's model of on-site CAR-T manufacturing using an internationally validated lentiviral vector platform (BIOCCUS, China) and automated closed-system bioreactor technology (CELLBRI) - analogous to the NexCAR19 program (ImmunoACT/IIT Bombay, India) in the LMIC context - provides a feasible, cost-recoverable, and sustainable approach to making this therapy accessible. This pilot study represents Pakistan's first academic CAR-T trial and aims to demonstrate manufacturing feasibility, safety, and early efficacy to support future regulatory approval and programme scale-up.
1.5 Investigational Product Description
The investigational product is autologous anti-CD19 CAR-T cells generated from patient-derived peripheral blood T cells using:
- Lentiviral vector: BIOCCUS-supplied, replication-deficient third-generation lentiviral vector encoding the anti-CD19 CAR transgene (CD19 scFv-CD8 hinge/TM-4-1BB-CD3ζ)
- Ex vivo manufacturing: CELLBRI automated closed-system bioreactor platform at AFBMTC GMP-equivalent cell therapy laboratory
- CAR construct: Single-chain variable fragment (scFv) targeting human CD19, fused to CD8α hinge and transmembrane domain, 4-1BB (CD137) costimulatory domain, and CD3ζ activation domain
- Cell source: Non-mobilised leukapheresis product from the patient
- Administration: Single intravenous infusion following lymphodepleting chemotherapy
- Being tested
- CAR-T cell infusion
- Keywords
- B-ALL, Relapsed, Refractory, Adult, Childhood
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAR-T cell infusionBiological
CAR-T Cell infusion therapy will be given
| Study group | Role | What they receive |
|---|---|---|
| CAR-T arm | Other | 5.1 Leukapheresis Leukapheresis will be performed at AFBMTC using standard large-volume apheresis technique on a validated apheresis platform. Non-mobilised peripheral blood mononuclear cells (PBMCs) will be collected targeting ≥1 × 10⁸ CD3+ T cells/kg (paediatric) or a minimum of 5 × 10⁸ CD3+ T cells total (adult). Pre-apheresis ALC and CD3+ count must both exceed 100/µL. Leukapheresis products will be processed immediately for manufacturing or cryopreserved in validated storage at AFBMTC.
5.2 CAR-T Cell Manufacturing 5.2.1 Vector Platform The anti-CD19 CAR transgene will be delivered using a replication-deficient, self-inactivating (SIN) third-generation lentiviral vector supplied by BIOCCUS (China). The vector encodes: anti-CD19 scFv (murine or humanised) - CD8α hinge/transmembrane domain - 4-1BB costimulatory domain - CD3ζ activation domain. The lentiviral vector backbone incorporates safety modifications including deletion of viral enhancer elements in the 3' LTR (self-inactivati Receives: Biological: CAR-T cell infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the safety and feasibility of autologous anti-CD19 CAR-T cell therapy manufactured at AFBMTC using the BIOCCUS lentiviral vector and CELLBRI automated expansion system in patients aged 5-50 years with relapsed or refractory B-cell ALL.
Primary Safety Incidence/grade of CRS (ASTCT) Day 0-28
Measured: 1 year after infusion of CAR-T
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2026
- Study start1 Jun 2026
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Relapsed Acute Lymphoblastic Leukemia (ALL)Studies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dr. Zaineb Akram
- Sponsor type
- Other government
- Responsible party
- Sponsor-investigator, Dr. Zaineb Akram, National Institute of Blood and Marrow Transplant (NIBMT), Pakistan
- Investigators
- Maryam Khan, MBBS, MRCP (UK), FCPS(Cl Haem), Study chair, National University of Medical SciencesTariq Ghafoor, Principal investigator, National University of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07695012
- Sponsor's protocol ID
- PAKCAR-ALL-01
- Acronym
- PAKCAR-ALL
- Status last verified
- Jul 2026
- First submitted
- 27 Jun 2026
- Last updated
- 10 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD will be shared after enrollment is complete and upon request by email
Publications
. Sharma P, Srikantaiah V, Mitra S, et al. NexCAR19: indigenously developed anti-CD19 CAR-T in India - results from Phase I/II study. Indian J Hematol Blood Transfus. 2023 [LMIC reference].
Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. doi: 10.1056/NEJMoa1707447. Epub 2017 Dec 10.
PubMed 29226797Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, Teachey DT, Chew A, Hauck B, Wright JF, Milone MC, Levine BL, June CH. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013 Apr 18;368(16):1509-1518. doi: 10.1056/NEJMoa1215134. Epub 2013 Mar 25.
PubMed 23527958Hay KA, Hanafi LA, Li D, Gust J, Liles WC, Wurfel MM, Lopez JA, Chen J, Chung D, Harju-Baker S, Cherian S, Chen X, Riddell SR, Maloney DG, Turtle CJ. Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T-cell therapy. Blood. 2017 Nov 23;130(21):2295-2306. doi: 10.1182/blood-2017-06-793141. Epub 2017 Sep 18.
PubMed 28924019Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S, Go WY, Eldjerou L, Gardner RA, Frey N, Curran KJ, Peggs K, Pasquini M, DiPersio JF, van den Brink MRM, Komanduri KV, Grupp SA, Neelapu SS. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019 Apr;25(4):625-638. doi: 10.1016/j.bbmt.2018.12.758. Epub 2018 Dec 25.
PubMed 30592986Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, Qayed M, De Moerloose B, Hiramatsu H, Schlis K, Davis KL, Martin PL, Nemecek ER, Yanik GA, Peters C, Baruchel A, Boissel N, Mechinaud F, Balduzzi A, Krueger J, June CH, Levine BL, Wood P, Taran T, Leung M, Mueller KT, Zhang Y, Sen K, Lebwohl D, Pulsipher MA, Grupp SA. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med. 2018 Feb 1;378(5):439-448. doi: 10.1056/NEJMoa1709866.
PubMed 29385370
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot, Single-Arm, Open-Label Feasibility Study of Autologous Anti-CD19 Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Pediatric and Young Adult Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia (r/r B-ALL)
- ClinicalTrials.gov ID
- NCT07695012
- Acronym / sponsor ID
- PAKCAR-ALL / PAKCAR-ALL-01
- Keywords
- B-ALL, Relapsed, Refractory, Adult, Childhood
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Dr. Zaineb AkramOther government
- Study start
- 1 Jun 2026 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 10 Jul 2026 (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.
Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and the second most frequent acute leukemia in adults. B-cell ALL constitutes approximately 85% of all ALL diagnoses. In Pakistan, ALL represents the most prevalent haematological malignancy presenting to tertiary centres, with AFBMTC receiving the largest national referral volume for haematological malignancies and transplantation.
First-line combination chemotherapy achieves complete remission (CR) in >95% of paediatric patients; however, 15-20% relapse. Outcomes following first relapse are substantially inferior: second-line salvage chemotherapy achieves CR2 in 30-50% of patients, and long-term event-free survival (EFS) after conventional chemotherapy alone is <10%. Outcomes in adult ALL are even more dismal, with OS at 5 years below 40% even in first CR without allogeneic transplant.
Patients with primary refractory ALL or multiply relapsed ALL have an unmet medical need for novel therapeutic approaches. The classical paradigm of chemotherapy followed by allogeneic haematopoietic stem cell transplantation (allo-HSCT) is limited by donor availability, conditioning-related mortality, and inability to achieve remission before transplant.
Detailed description
1.2 CD19 as a Therapeutic Target CD19 is a B-lineage surface glycoprotein expressed on the majority of B-cell ALL blasts, retained through disease evolution, and absent on haematopoietic stem cells, non-haematopoietic tissues, and most normal tissues. CD19 expression is confirmed in >95% of B-ALL cases, making it the optimal target for immunotherapy. The only significant on-target off-tumour consequence is B-cell aplasia and hypogammaglobulinaemia, which are clinically manageable with immunoglobulin replacement.
1.3 CAR-T Cell Therapy: Scientific and Clinical Rationale Chimeric antigen receptor T-cell (CAR-T) therapy involves ex vivo genetic modification of autologous T cells to express a synthetic receptor comprising: (1) an extracellular antigen-binding domain (anti-CD19 scFv), (2) a hinge and transmembrane domain, (3) an intracellular costimulatory domain (4-1BB/CD137), and (4) a CD3ζ signalling domain. Upon infusion, CAR-T cells recognise CD19+ target cells in an MHC-independent manner, inducing direct cytotoxicity, cytokine release, and in vivo proliferation.
The 4-1BB costimulatory domain (used in this protocol) confers superior persistence and memory formation compared to CD28-based constructs, as demonstrated in seminal studies from the University of Pennsylvania and subsequently confirmed in the ELIANA global Phase II trial of tisagenlecleucel (Maude et al., NEJM 2018), which demonstrated an overall remission rate of 81% and 12-month EFS of 50% in heavily pre-treated paediatric and young adult r/r B-ALL.
1.4 Institutional Rationale and LMIC Context AFBMTC is Pakistan's first and largest haematology and cellular therapy centre, established in 2001 under NUMS, with a cumulative experience of >2,000 allogeneic, autologous, and haploidentical HSCTs. AFBMTC possesses critical institutional infrastructure for CAR-T implementation including GMP-equivalent cleanroom facilities, validated cryopreservation and leukapheresis capabilities, and an established mesenchymal stromal cell (MSC) GMP program with over a decade of experience - directly translatable to CAR-T manufacturing quality standards.
Access to commercially approved CAR-T products (tisagenlecleucel, axicabtagene ciloleucel) is prohibitively expensive and effectively unavailable in Pakistan. AFBMTC's model of on-site CAR-T manufacturing using an internationally validated lentiviral vector platform (BIOCCUS, China) and automated closed-system bioreactor technology (CELLBRI) - analogous to the NexCAR19 program (ImmunoACT/IIT Bombay, India) in the LMIC context - provides a feasible, cost-recoverable, and sustainable approach to making this therapy accessible. This pilot study represents Pakistan's first academic CAR-T trial and aims to demonstrate manufacturing feasibility, safety, and early efficacy to support future regulatory approval and programme scale-up.
1.5 Investigational Product Description
The investigational product is autologous anti-CD19 CAR-T cells generated from patient-derived peripheral blood T cells using:
- Lentiviral vector: BIOCCUS-supplied, replication-deficient third-generation lentiviral vector encoding the anti-CD19 CAR transgene (CD19 scFv-CD8 hinge/TM-4-1BB-CD3ζ)
- Ex vivo manufacturing: CELLBRI automated closed-system bioreactor platform at AFBMTC GMP-equivalent cell therapy laboratory
- CAR construct: Single-chain variable fragment (scFv) targeting human CD19, fused to CD8α hinge and transmembrane domain, 4-1BB (CD137) costimulatory domain, and CD3ζ activation domain
- Cell source: Non-mobilised leukapheresis product from the patient
- Administration: Single intravenous infusion following lymphodepleting chemotherapy
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CAR-T arm | Other | Biological: CAR-T cell infusion5.1 Leukapheresis Leukapheresis will be performed at AFBMTC using standard large-volume apheresis technique on a validated apheresis platform. Non-mobilised peripheral blood mononuclear cells (PBMCs) will be collected targeting ≥1 × 10⁸ CD3+ T cells/kg (paediatric) or a minimum of 5 × 10⁸ CD3+ T cells total (adult). Pre-apheresis ALC and CD3+ count must both exceed 100/µL. Leukapheresis products will be processed immediately for manufacturing or cryopreserved in validated storage at AFBMTC. 5.2 CAR-T Cell Manufacturing 5.2.1 Vector Platform The anti-CD19 CAR transgene will be delivered using a replication-deficient, self-inactivating (SIN) third-generation lentiviral vector supplied by BIOCCUS (China). The vector encodes: anti-CD19 scFv (murine or humanised) - CD8α hinge/transmembrane domain - 4-1BB costimulatory domain - CD3ζ activation domain. The lentiviral vector backbone incorporates safety modifications including deletion of viral enhancer elements in the 3' LTR (self-inactivati |
Who may qualify
- Ages
- 5 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (44 listed)
- 1. Age ≥5 years and ≤50 years at the time of consent
- 2. Morphologically or immunophenotypically confirmed B-cell ALL (CD19+) meeting one or more of the following relapsed/refractory criteria:
- 3. CD19 expression on tumour cells confirmed by multi-parameter flow cytometry within 3 months of enrolment (≥20% CD19-positive blasts required)
- 4. Bone marrow blast burden ≥5% by morphological assessment at screening
- 5. Adequate organ function at screening:
Key exclusion criteria (1 listed)
- -
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 infusionCAR-T Cell infusion therapy will be given | Biological | CAR-T arm |
Primary outcome
To evaluate the safety and feasibility of autologous anti-CD19 CAR-T cell therapy manufactured at AFBMTC using the BIOCCUS lentiviral vector and CELLBRI automated expansion system in patients aged 5-50 years with relapsed or refractory B-cell ALL.
Time frame: 1 year after infusion of CAR-T
Primary Safety Incidence/grade of CRS (ASTCT) Day 0-28
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2026.
- Background. Sharma P, Srikantaiah V, Mitra S, et al. NexCAR19: indigenously developed anti-CD19 CAR-T in India - results from Phase I/II study. Indian J Hematol Blood Transfus. 2023 [LMIC reference].
- Background: PubMed 29226797Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. doi: 10.1056/NEJMoa1707447. Epub 2017 Dec 10.
- Background: PubMed 23527958Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, Teachey DT, Chew A, Hauck B, Wright JF, Milone MC, Levine BL, June CH. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013 Apr 18;368(16):1509-1518. doi: 10.1056/NEJMoa1215134. Epub 2013 Mar 25.
- Background: PubMed 28924019Hay KA, Hanafi LA, Li D, Gust J, Liles WC, Wurfel MM, Lopez JA, Chen J, Chung D, Harju-Baker S, Cherian S, Chen X, Riddell SR, Maloney DG, Turtle CJ. Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T-cell therapy. Blood. 2017 Nov 23;130(21):2295-2306. doi: 10.1182/blood-2017-06-793141. Epub 2017 Sep 18.
- Background: PubMed 30592986Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S, Go WY, Eldjerou L, Gardner RA, Frey N, Curran KJ, Peggs K, Pasquini M, DiPersio JF, van den Brink MRM, Komanduri KV, Grupp SA, Neelapu SS. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019 Apr;25(4):625-638. doi: 10.1016/j.bbmt.2018.12.758. Epub 2018 Dec 25.
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- Individual participant dataSharing planned: Yes. IPD will be shared after enrollment is complete and upon request by email
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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.
Maryam Khan, MBBS, MRCP (UK), FCPS(Cl Haem) study chair
National University of Medical Sciences
Tariq Ghafoor principal investigator
National University of Medical Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing CAR-T cell infusion in people with Relapsed Acute Lymphoblastic Leukemia (ALL), run by Dr. Zaineb Akram at 1 site in Pakistan.
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 44 inclusion and 1 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: looking for participants now, as of the sponsor's last update on 10 Jul 2026. 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 Pakistan. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nadia Sial, Ph.D (+923315582265, nadiaharif@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the safety and feasibility of autologous anti-CD19 CAR-T cell therapy manufactured at AFBMTC using the BIOCCUS lentiviral vector and CELLBRI automated expansion system in patients aged 5-50 years with relapsed or refractory B-cell ALL. (time frame: 1 year after infusion of CAR-T). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07695012, which also lists 6 linked publications.
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 10 Jul 2026.