Clinical Trial Using CAR- T Cells for Treatment of Patients With Refractory or Relapsed CD19-positive B Lymphoid Malignancies

NCT05705570 | Recruiting Phase 1 DMC

• 1 other identifier: 30173220.5.0000.0071
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase l, single arm, prospective open, dose-escalation study in patients with relapsed or refractory CD19-positive B cell malignancies (ALL, NHL, CLL). The trial will include adult and pediatric patients. There will be three individual cohorts, defined by disease biology: pediatric ALL and aggressive pediatric NHL (Cohort 1), adult ALL (Cohort 2) and adult NHL/CLL (Cohort 3).

Conditions

Acute Lymphoblastic Leukemia, in Relapse; Acute Lymphoblastic Leukemia Refractory; B-cell Lymphoma Recurrent; B-cell Lymphoma Refractory; Chronic Lymphocytic Leukemia Recurrent; Chronic Lymphocytic Leukemia Refractory

Keywords

CAR T cell; CD19+ B-cell Malignancies

Outcome Measures

Primary Outcomes (1)

• Determination of the recommended dose of CAR-T cells for a future phase II study

  The RP2D will be the maximum tolerated dose (MTD) or the highest dose studied if an MTD is not obtained.

  Until day 28 after CAR-T cells infusion

Secondary Outcomes (4)

• Response to treatment for each timepoint.

  day 28

• Response to treatment for each timepoint

  day 28, patients not in CR on day 28: month 3

• Assess overall survival (OS), progression-free survival (PFS).

  at 1 year after CAR-T infusion

• Phenotype and persistence of CAR-T

  days 2, 7, 10, 14, 28, weeks 8, 12, months 6, 12, 24, 36, 48, 60

Study Arms (1)

Cyclophosphamide + Fludarabine + Infusion of CAR-T Cells

EXPERIMENTAL

Lymphodepleting regimen, consisting of Cyclophosphamide 60mg/kg IV on day -6 and Fludarabine 25mg/m2 IV on days -5 to -3. Followed by infusion of Chimeric antigen receptor T-cells (CAR-T) on day 0

Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Chimeric antigen receptor T cells to be implemented in a "3 + 3" design on day 0

Interventions

Cyclophosphamide DRUG

Cyclophosphamide 60mg/Kg on day -6

Cyclophosphamide + Fludarabine + Infusion of CAR-T Cells

Fludarabine DRUG

Fludarabine 25mg/m\^2 IV on days -5 to -3

Cyclophosphamide + Fludarabine + Infusion of CAR-T Cells

Chimeric antigen receptor T cells to be implemented in a "3 + 3" design on day 0 BIOLOGICAL

Level -1 (1 x 105 cells/kg) Level 1 \[Starting dose\] (5 x 105 cells/kg) Level 2 (1 x 106 cells/kg) Level 3 (2 x 106 cells/kg)

Cyclophosphamide + Fludarabine + Infusion of CAR-T Cells

Eligibility Criteria

• Age: 2 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have relapsed or refractory ALL, lymphoma or CLL treated with at least two lines of therapy. Disease must have either progressed after the last regimen or presented failure to achieve partial or complete remission with the last regimen.
• Subjects with Philadelphia Chromosome positive acute lymphoblastic leukemia (Ph+ALL) subjects are eligible if they progressed, had stable disease or relapsed after two lines of therapy, including tyrosine kinase inhibitors (TKIs).
• Subjects with DLBCL must have progressed, had SD, or recurred after initial treatment regimens that include an anthracycline and an anti-CD20 monoclonal antibody.
• Subjects with transformed FL, MZL, or CLL/SLL must have progressed, had SD or recurred with transformed disease after initial treatment for DLBCL.
• Subjects who relapse ≥12 months after therapy should have progressed after autologous transplant or been ineligible for autologous transplant.
• \. The patient's disease must be CD19 positive, either by immunohistochemistry or flow cytometry analysis on the last biopsy available.
• Age 2 to 70 years.
• Performance status: Adult Subjects: ECOG ≤ 2 for patients ≥ 16 years; Subjects \< 16 years of age: lansky ≥ 50%
• Normal Organ and Marrow Functioning (supportive treatment is allowed according to institutional standards, i.e. filgrastim, transfusion)
• Total Bilirubin ≤ 2; AST (SGOT) ≤ 5 times the upper limit of normal; ALT (SGTP) ≤ 5 times the upper limit of normal; Serum creatinine ≤ 1.5; Pulse oximetry \>91% on room air; No dyspnea or mild dyspnea (≤ Grade 1); Forced expiratory volume in 1 s (FEV1) ≥50% or carbon monoxide diffusion test (DLCO) ≥50% of predicted level; Left ventricular ejection fraction ≥ 45% confirmed by echocardiogram; Subjects must have the following hematologic function parameters: Neutrophils \> 1000/uL; Absolute Lymphocyte Count \> 100/uL; Platelets ≥ 50,000/L Patient should not be excluded if change of the above parameters due to spinal cord disease infiltration;
• Prior therapy wash-out - At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy, which requires 5 half-lives, Blinatumomab with 4 months prior CAR-T infusion.
• For women of reproductive potential: use a highly effective contraceptive for at least 1 month prior to screening and agree to use a method during study participation and for an additional 4 months after CAR T-cell administration has ended.
• Subjects must have the ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Autologous transplant within 6 weeks of planned CAR-T cell infusion;
• History of allogeneic stem cell transplant 4 months prior CAR T cell infusion.
• Use of immunosuppression therapy;
• Patients must have completed immunosuppression therapy; Systemic corticosteroid therapy must be stopped more than 72 hours after infusion; Systemic drugs for graft-versus-host disease should be withheld at least 4 weeks prior to infusion;
• Presence of graft-versus-host disease Grade ≥ 2;
• Receiving CAR T cell treatment outside of this protocol;
• Active central nervous system or meningeal involvement by tumor. Subjects with untreated brain metastases/CNS disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with a history of CNS or meningeal involvement must be in a documented remission by CSF evaluation and contrast-enhanced MRI imaging for at least 90 days prior to registration.
• History of active malignancy other than non-melanoma skin cancer, carcinoma in situ (e.g. cervix, bladder, breast).
• HIV infection; HTLV
• Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or breastfeeding women are excluded from this study because CAR-T cell therapy may be associated with the potential for teratogenic or abortifacient effects.
• Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy
• Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.)
• Serious and/or potentially fatal medical conditions
• Patients with history of clinically relevant CNS pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease.

Sponsors & Collaborators

• Nelson Hamerschlak: lead
• Miltenyi Biotec, Inc.: collaborator

Study Sites (1)

Hospital Israelita Albert Einstein

São Paulo, São Paulo, 05652-900, Brazil

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Nelson Hamerschlak, MD, PhH

  Hospital Israelita Albert Einstein

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nelson Hamerschlak, MD, PhH

CONTACT

+551121517248; hamer@einstein.br

Lucila N Kerbauy, MD, PhD

CONTACT

+5511998667557; lucila.kerbauy@einstein.br

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhH

Model Details: A phase I study, with a "3+3" dose escalation design

Study Record Dates

• First Submitted: January 20, 2023
• First Posted: January 31, 2023
• Study Start: February 7, 2023
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)