What side effects are associated with this type of intervention?

The most common side effects of CAR-T cell therapy, such as Tisagenlecleucel, for treating Acute Lymphoblastic Leukemia include cytokine release syndrome (CRS) and neurologic events. CRS can present with symptoms like fever, chills, and low blood pressure, and in severe cases, it can lead to organ dysfunction. Neurologic events may include confusion, seizures, and encephalopathy. Other side effects can include cytopenias (low blood cell counts), infections, and fatigue. These side effects are generally manageable with supportive care and specific treatments like tocilizumab for CRS.

What prior FDA approvals exist?

The FDA has approved several CAR-T cell therapies for the treatment of Acute Lymphoblastic Leukemia (ALL). Tisagenlecleucel (Kymriah) was the first CAR-T cell therapy approved by the FDA in 2017 for the treatment of pediatric and young adult patients with relapsed or refractory B-cell ALL. This therapy involves modifying a patient's T cells to target and kill B cells expressing the CD19 antigen. Another similar CAR-T cell therapy is Axicabtagene Ciloleucel (Yescarta), which, while primarily approved for certain types of non-Hodgkin lymphoma, also targets CD19 on B cells and represents a similar approach in immunotherapy.

What other types of research exist?

Promising novel alternatives to Tisagenlecleucel for Acute Lymphoblastic Leukemia patients include: 1) Other CAR-T cell therapies such as Brexucabtagene autoleucel, which targets CD19 and has shown efficacy in relapsed or refractory B-cell ALL. 2) Bispecific T-cell engagers (BiTEs) like Blinatumomab, which directs T-cells to target CD19-positive B-cells. 3) Antibody-drug conjugates such as Inotuzumab ozogamicin, which targets CD22 on B-cells. These therapies offer different mechanisms of action and have demonstrated promising results in clinical settings.

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CAR T-cell Therapy

Second Infusion of Tisagenlecleucel for Acute Lymphoblastic Leukemia

Phase 2

Recruiting

Led By Kevin Curran, MD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be younger than 65 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year

Awards & highlights

Study Summary

This trial is to see if an early second infusion of tisagenlecleucel can keep B-cell aplasia at bay for longer. They will also assess safety and efficacy.

Who is the study for?

This trial is for children and young adults under 26 with B-cell Acute Lymphoblastic Leukemia who've had a previous tisagenlecleucel infusion. They must have normal organ function, no severe ongoing side effects from the first treatment, and not be pregnant or breastfeeding. Participants need to agree to use contraception if applicable.Check my eligibility

What is being tested?

The study tests whether an early second dose of tisagenlecleucel can maintain cancer remission at six months post-first infusion in patients with B-ALL. It also evaluates the safety and effectiveness of this reinfusion strategy.See study design

What are the potential side effects?

Potential side effects include reactions related to immune system activation such as fever, difficulty breathing, rapid heartbeat, feeling weak or tired; neurological issues like confusion or seizures; liver problems; low blood cell counts increasing infection risk.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 year for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

decrease the loss of peripheral BCA rate

Secondary outcome measures

number and percentage of toxicities with early reinfusion of CAR T cells

Side effects data

From 2022 Phase 2 trial • 115 Patients • NCT02445248

48%

Anaemia

41%

Cytokine release syndrome

36%

White blood cell count decreased

35%

Neutrophil count decreased

33%

Platelet count decreased

31%

Diarrhoea

30%

Pyrexia

29%

Nausea

24%

Fatigue

24%

Hypotension

23%

Hypokalaemia

21%

Headache

18%

Neutropenia

17%

Constipation

17%

Hypomagnesaemia

17%

Hypophosphataemia

17%

Cough

15%

Oedema peripheral

14%

Arthralgia

14%

Dyspnoea

13%

Thrombocytopenia

13%

Upper respiratory tract infection

13%

Decreased appetite

12%

Chills

12%

Dizziness

12%

Weight decreased

10%

Febrile neutropenia

10%

Tachycardia

10%

Blood creatinine increased

10%

Anxiety

Urinary tract infection

Pain in extremity

Hypogammaglobulinaemia

Abdominal pain

Hyponatraemia

Vomiting

Influenza like illness

Nasopharyngitis

Pneumonia

Insomnia

Asthenia

Sinusitis

Confusional state

Hypoxia

Back pain

Stomatitis

Influenza

Blood immunoglobulin G decreased

Lymphocyte count decreased

Myalgia

Dry mouth

Pain

Hypocalcaemia

Pleural effusion

Rash

Acute kidney injury

Oropharyngeal pain

Night sweats

Myelodysplastic syndrome

Multiple organ dysfunction syndrome

Clostridium difficile infection

Sepsis

Encephalopathy

Prostate cancer

Pancytopenia

Bone marrow failure

Gastrointestinal haemorrhage

Infection

Respiratory tract infection

Staphylococcal infection

Dehydration

Respiratory failure

Pneumocystis jirovecii pneumonia

Pulmonary embolism

Neuroendocrine carcinoma

Vaginal infection

Malignant melanoma

C-reactive protein increased

Urosepsis

Bronchopulmonary aspergillosis

Polyarthritis

Pulmonary haemorrhage

Acute myeloid leukaemia

Atrial fibrillation

Cardiac arrest

Cardio-respiratory arrest

Cardiopulmonary failure

Vertigo

Anal fissure

Duodenal ulcer haemorrhage

Haematemesis

Large intestinal obstruction

Melaena

Pancreatitis acute

Face oedema

Cholecystitis acute

Atypical pneumonia

Bronchitis

Cerebral toxoplasmosis

Corynebacterium infection

Escherichia infection

Lower respiratory tract infection

Systemic infection

Blood bilirubin increased

Liver function test increased

Hypercalcaemia

Tumour lysis syndrome

Acute polyneuropathy

Cerebral haemorrhage

Demyelinating polyneuropathy

Ischaemic cerebral infarction

Metabolic encephalopathy

Somnolence

Status epilepticus

Mental status changes

Chronic kidney disease

Urinary tract obstruction

Allergic bronchitis

Asphyxia

Pneumonitis

Deep vein thrombosis

Lymphadenopathy

Cardiac failure congestive

Candida infection

Upper limb fracture

Refractory cytopenia with multilineage dysplasia

Pharyngeal haemorrhage

Haemophagocytic lymphohistiocytosis

Myopathy

Tumour haemorrhage

Pneumonia aspiration

Pseudomonas infection

Tumour associated fever

Invasive ductal breast carcinoma

Cystitis haemorrhagic

Infusion related reaction

Syncope

Hepatic failure

100%

80%

60%

40%

20%

Study treatment Arm

Tisagenlecleucel - All Patients

Trial Design

1Treatment groups

Experimental Treatment

Group I: TisagenlecleucelExperimental Treatment1 Intervention

Patients will receive reinfusion of tisagenlecleucel on day +30-60 after their initial infusion if meeting eligibility criteria. Tisagenlecleucel is an autologous cellular immunotherapy product that is comprised of CD3+T cells that have undergone ex vivo T cell activation, gene modification, expansion, and formulation in infusible cryomedia.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Tisagenlecleucel

2019

Completed Phase 2

~360

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

CAR-T cell therapy, such as Tisagenlecleucel, involves modifying a patient's own T cells to express a chimeric antigen receptor (CAR) that specifically targets CD19, a protein found on the surface of B cells, including malignant B cells in B-cell acute lymphoblastic leukemia (B-ALL). Once these engineered T cells are infused back into the patient, they can recognize and kill the cancerous B cells. This targeted approach is significant for ALL patients because it offers a personalized treatment option that can lead to sustained remissions, especially in cases where the disease is refractory or has relapsed after conventional therapies. Other common treatments for ALL include chemotherapy, which targets rapidly dividing cells, and hematopoietic stem cell transplantation, which aims to replace diseased bone marrow with healthy cells. However, CAR-T cell therapy represents a major advancement due to its specificity and potential for long-term remission.

Favorable Activity and Safety Profile of Memory-Enriched CD19-Targeted Chimeric Antigen Receptor T Cell Therapy in Adults with high-risk Relapsed/Refractory ALL.