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Updated May 2026 · ClinicalTrials.gov

RECRUITINGPhase 1 / Phase 2INTERVENTIONAL

Treatment of Patients With Relapsed or Refractory CD19+ Lymphoid Disease With T Cells Expressing a Third-generation CAR

Treatment of Patients With Relapsed or Refractory CD19+ Lymphoid Disease With T Lymphocytes Transduced by RV-SFG.CD19.CD28.4-1BBzeta Retroviral Vector - a Unicenter Phase I/II Clinical Trial

Treatment of Patients With Relapsed or Refractory CD19+ Lymphoid Disease With T Cells Expressing a Third-generation CAR (NCT03676504) is a Phase 1 / Phase 2 interventional studying Acute Lymphoblastic Leukemia, Adult and Acute Lymphoblastic Leukemia, Pediatric, sponsored by University Hospital Heidelberg. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

Adult patients with r/r acute lymphoblastic leukemia (ALL) (stratum I), r/r Non-Hodgkin's lymphoma (NHL) including chronic lymphocytic leukaemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) or mantle cell lymphoma (MCL) (stratum II) as well as paediatric patients with r/r ALL (stratum III) will be treated with autologous T-lymphocytes transduced by the third-generation RV-SFG.CD19.CD28.4-1BBzeta retroviral vector. The main purpose of this study is to evaluate safety and feasibility of escalating CD19.CAR T cell doses (0,1-20×20\^7 transduced cells/m\^2) after lymphodepletion with fludarabine and cyclophosphamide.

What Stage of Research Is This?

Phase 1 trials test a new treatment for the first time in humans, focusing on safety, dosing, and how the body processes the drug. For Acute Lymphoblastic Leukemia, Adult, a Phase 1 study typically enrolls a small number of participants — often healthy volunteers or patients who have exhausted standard treatment options. Phase 1 results determine whether a treatment moves into larger Phase 2 efficacy studies.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 68 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Acute Lymphoblastic Leukemia, Adult subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: Stratum I/II (Adults): - Confirmed CD19+ ALL, CLL, DLBCL, FL or MCL in patients ≥ 18 years - ALL (Ph+ and Ph-): Confirmed CD19+ ALL by cytology and flow cytometry (FACS) AND - Relapsed or refractory disease (including "molecular relapse" with minimal residual disease (MRD) levels \> 10\^-3 at two occasions \> 2 weeks apart) with confirmed CD19 expression on malignant cells in relapse - Any relapse after allogeneic stem cell transplantation (alloSCT) (≥ 6 months from alloSCT at time of CAR T cell infusion) OR - Any relapse failing to achieve an MRD level of \< 10\^-3 after ≥ 2 lines of treatment OR - Primary refractory as defined by not achieving a complete remission (CR) after ≥ 2 lines of treatment - CLL/NHL: Confirmed CD19+ CLL/NHL (including CLL, DLBCL, FL or MCL) with - CLL in need of treatment with: 1. Early relapse (within 2 years) after end of chemoimmunotherapy or chemoimmunotherapy refractoriness plus failure or intolerance of both Bruton's tyrosine kinase Inhibitor (BTKi) and B-cell lymphoma 2 inhibitors (BCL-2i) OR 2. Relapse after alloSCT, ineligible for or refractory to standard interventions (donor lymphocyte infusions (DLI), CD20 antibodies, chemoimmunotherapy) - DLBCL with: 1. Refractoriness to a 2nd or later line of chemoimmunotherapy OR 2. Relapse after autologous stem cell transplantation (autoSCT) plus ineligibility for alloSCT (including refractoriness to one line of salvage chemoimmunotherapy) OR 3. Relapse after alloSCT - FL in need of treatment with: 1. Relapse \<2 years after chemoimmunotherapy AND ineligibility for or failure of autologous stem cell transplantation (autoSCT) AND ineligibility for or failure of idelalisib OR 2. Relapse after alloSCT, ineligible for or refractory to standard interventions (DLI, CD20 antibodies, chemoimmunotherapy) - MCL with: 1. Relapse after standard first-line therapy AND ineligibility for or failure to BTKi salvage therapy OR ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: Stratum I/II (Adults): * Confirmed CD19+ ALL, CLL, DLBCL, FL or MCL in patients ≥ 18 years * ALL (Ph+ and Ph-): Confirmed CD19+ ALL by cytology and flow cytometry (FACS) AND * Relapsed or refractory disease (including "molecular relapse" with minimal residual disease (MRD) levels \> 10\^-3 at two occasions \> 2 weeks apart) with confirmed CD19 expression on malignant cells in relapse * Any relapse after allogeneic stem cell transplantation (alloSCT) (≥ 6 months from alloSCT at time of CAR T cell infusion) OR * Any relapse failing to achieve an MRD level of \< 10\^-3 after ≥ 2 lines of treatment OR * Primary refractory as defined by not achieving a complete remission (CR) after ≥ 2 lines of treatment * CLL/NHL: Confirmed CD19+ CLL/NHL (including CLL, DLBCL, FL or MCL) with * CLL in need of treatment with: 1. Early relapse (within 2 years) after end of chemoimmunotherapy or chemoimmunotherapy refractoriness plus failure or intolerance of both Bruton's tyrosine kinase Inhibitor (BTKi) and B-cell lymphoma 2 inhibitors (BCL-2i) OR 2. Relapse after alloSCT, ineligible for or refractory to standard interventions (donor lymphocyte infusions (DLI), CD20 antibodies, chemoimmunotherapy) * DLBCL with: 1. Refractoriness to a 2nd or later line of chemoimmunotherapy OR 2. Relapse after autologous stem cell transplantation (autoSCT) plus ineligibility for alloSCT (including refractoriness to one line of salvage chemoimmunotherapy) OR 3. Relapse after alloSCT * FL in need of treatment with: 1. Relapse \<2 years after chemoimmunotherapy AND ineligibility for or failure of autologous stem cell transplantation (autoSCT) AND ineligibility for or failure of idelalisib OR 2. Relapse after alloSCT, ineligible for or refractory to standard interventions (DLI, CD20 antibodies, chemoimmunotherapy) * MCL with: 1. Relapse after standard first-line therapy AND ineligibility for or failure to BTKi salvage therapy OR 2. Relapse after alloSCT AND ineligibility for or failure to BTKi salvage therapy * Measurable disease/MRD at time of enrollment * Life expectancy ≥ 12 weeks * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at the time of screening * Adequate organ function: * Renal function defined as: serum creatinine of ≤ 2 x ULN or estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m\^2 * Liver function defined as: * ALT ≤ 5 times the ULN for the respective age * Bilirubin ≤ 2.0 mg/dl with the exception of patients with hyperbilirubinemia explained by Gilbert-Meulengracht syndrome (may be included if total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN) or extrahepatic disease (e.g. chronic hemolytic anemia) * minimum level of pulmonary reserve defined as ≤ grade 1 dyspnea and pulse oxygenation \> 90% on room air * Hemodynamic stability and left ventricular ejection fraction (LVEF) ≥ 40% as confirmed by echocardiogram * Absolute neutrophil count (ANC) ≥ 500/mm3 * Absolute lymphocyte count (ALC) ≥ 100/mm3 * Women of child-bearing potential (defined as all women physiologically capable of becoming pregnant) and all male participants must agree to use highly effective methods of contraception for one year following CD19.CAR T cell therapy * Ability to understand the nature of the trial and the trial related procedures * Written informed consent must be obtained prior to any screening procedures Stratum III (Children and Adolescents with ALL): * Age of \> 3 years until \< 18 years at the time of screening * CD19+ ALL (Ph+ and Ph-) confirmed by cytology and flow cytometry (FACS) AND * Relapsed or refractory disease (including "molecular relapse" with polymerase chain reaction (PCR) MRD \> 10\^-3 at two occasions \> 2 weeks apart) with confirmed CD19 expression on malignant cells in relapse * Any relapse after alloSCT (≥ 6 months from alloSCT at time of CAR T cell infusion) OR * Any relapse failing to achieve an MRD level of \< 10\^-3 after ≥ 2 lines of treatment OR * Primary refractory as defined by not achieving a CR after ≥ 2 lines of treatment * Measurable disease/MRD at time of enrollment * Life expectancy ≥ 12 weeks * ECOG performance status ≤ 2 (age ≥ 16 years) or Lansky performance status ≥ 50 (age \< 16 years) at the time of screening * Adequate organ function: * Renal function defined as serum creatinine-clearance ≥ 30 mL/min/1.73 m\^2 * Liver function defined as: * ALT ≤ 5 times the ULN for the respective age * Bilirubin ≤ 2.0 mg/dl with the exception of patients with hyperbilirubinemia explained by Gilbert-Meulengracht syndrome or extrahepatic disease (e.g. chronic hemolytic anemia) * minimum level of pulmonary reserve defined as ≤ grade 1 dyspnea and pulse oxygenation \> 90% on room air * Hemodynamic stability and LVEF ≥ 40% or shortening fraction \> 29% as confirmed by echocardiogram * ANC) ≥ 500/mm3 * ALC ≥ 100/mm3 * Women of child-bearing potential (defined as all women physiologically capable of becoming pregnant) and postpubertal male participants must agree to use highly effective methods of contraception for one year following CD19.CAR T cell therapy * Written informed consent of the study patient and/or the legal representative must be obtained prior to any screening procedures Exclusion Criteria: Stratum I/II (Adults): * The following medications are excluded: * Immunosuppressive medication with the exception of ≤ 30 mg prednisolone/d or equivalent at the time of CAR T cell transfusion * Bridging/maintenance therapy including chemo- and immunotherapy must be stopped ≥ 2 weeks prior to leukapheresis, but can be continued between leukapheresis and lymphodepletion * Intrathecal chemotherapy is possible at any time, but not during lymphodepletion until 14 days after CD19.CAR T cell transfusion * Any DLI must be completed \> 6 weeks prior to CD19.CAR T cell infusion * Florid/acute or chronic Graft-versus-Host disease (GvHD) * Uncontrolled active hepatitis B or C * HIV-positivity * Uncontrolled acute life-threatening bacterial, viral or fungal infection * Severe concomitant disease (e.g. uncontrolled arterial hypertension, heart failure New York Heart Association (NYHA) III-IV, uncontrolled diabetes mellitus, uncontrolled hyperlipidemia) * Unstable angina and/or myocardial infarction within 3 months prior to screening * Any previous or concurrent malignancy. The following exceptions do NOT constitute exclusion criteria: * Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to study entry) * In situ carcinoma of the cervix or breast, treated curatively without evidence of recurrence ≥ 3 years prior to the study * CLL or FL transformed into an aggressive B cell lymphoma * A primary malignancy which is in complete remission for ≥ 5 years * Pregnant or nursing (lactating) women * Intolerance to the excipients of the cell product * Active central nervous System (CNS) involvement in ALL patient at the time of screening is not an exclusion criterion, but patients with CNS 3 status at clinical screening (d-14) are not eligible for CD19.CAR T cell transfusion * Participation in another clinical trial at the time of screening Stratum III (Children and Adolescents with ALL): * The following medications are excluded: * immunosuppressive medication with the exception of \< 0.5 mg/d\*kg body weight (BW) prednisolone-equivalent at the time of CD19.CAR T cell transfusion * Bridging/Maintenance therapy including chemo- and immunotherapy must be stopped ≥ 2 weeks prior to leukapheresis, but can be continued between leukapheresis and lymphodepletion * Intrathecal chemotherapy is possible at any time, but not during lymphodepletion until 14 days after CD19.CAR T cell transfusion * Any DLI must be completed \> 6 weeks prior to CD19.CAR T cell infusion * Florid/acute or chronic GvHD * Uncontrolled active hepatitis B or C * HIV-positivity * Uncontrolled acute life-threatening bacterial, viral or fungal infection * Severe concomitant disease (e.g. any life-limiting genetic disorder). Patients with Down Syndrome will not be excluded. * Any previous or concurrent malignancy. The following exceptions do not constitute exclusion criteria: * Lymphoblastic lymphoma transformed into a CD19+ acute lymphoblastic leukemia * A primary malignancy which is in complete remission for ≥ 5 years * Pregnant or nursing (lactating) women * Intolerance to the excipients of the cell product * Active CNS involvement at the time of screening is not an exclusion criterion, but patients with CNS 3 status at clinical screening (d-14) are not eligible for CD19.CAR T cell transfusion * Participation in another clinical trial at the time of screening

Treatments Being Tested

BIOLOGICAL

CD19.CAR T Cells

Dose Level 1: 1×10\^6 transduced cells/m\^2; Dose Level 2: 5×10\^6 transduced cells/m\^2; Dose Level 3: 20×10\^6 transduced cells/m\^2; Dose Level 4: 5x10\^7 transduced cells/m\^2; Dose Level 5: 10x10\^7 transduced cells/m\^2; Dose Level 6: 20x10\^7 transduced cells/m\^2

DRUG

Fludarabine

3 days of fludarabine 30 mg/m\^2/day

DRUG

Cyclophosphamide

3 days of cyclophosphamide 500 mg/m\^2/day

Locations (2)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

University Hospital Heidelberg
Heidelberg, Germany
University Hospital Heidelberg
Heidelberg, Germany

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT03676504), the sponsor (University Hospital Heidelberg), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT03676504 clinical trial studying?

Adult patients with r/r acute lymphoblastic leukemia (ALL) (stratum I), r/r Non-Hodgkin's lymphoma (NHL) including chronic lymphocytic leukaemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) or mantle cell lymphoma (MCL) (stratum II) as well as paediatric patients with r/r ALL (stratum III) will be treated with autologous T-lymphocytes transduced by the third-generation RV-SFG.CD19.CD28.4-1BBzeta retroviral vector. The main purpose of this study is to evaluate safety and feasibility of escalating CD19.CAR T cell doses (0,1-20×20\^7 transduced cells/m\^2) after lymphode… The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT03676504?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT03676504?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT03676504. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT03676504. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.