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

No Placebo-Only Group

Summary

This trial is testing if using the body's own immune system can help patients with a specific type of leukemia stay in a stable condition. It also looks at the safety and effectiveness of this approach. The treatment works by boosting the body's own immune system to better fight cancer.

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.

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.

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

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

decrease the loss of peripheral BCA rate

Secondary study objectives

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%

Hypotension

24%

Fatigue

23%

Hypokalaemia

21%

Headache

18%

Neutropenia

17%

Constipation

17%

Hypophosphataemia

17%

Hypomagnesaemia

17%

Cough

15%

Oedema peripheral

14%

Arthralgia

14%

Dyspnoea

13%

Decreased appetite

13%

Thrombocytopenia

13%

Upper respiratory tract infection

12%

Weight decreased

12%

Dizziness

12%

Chills

10%

Tachycardia

10%

Blood creatinine increased

10%

Anxiety

10%

Febrile neutropenia

Hypogammaglobulinaemia

Urinary tract infection

Pain in extremity

Hyponatraemia

Vomiting

Influenza like illness

Nasopharyngitis

Pneumonia

Abdominal pain

Asthenia

Sinusitis

Confusional state

Insomnia

Hypoxia

Stomatitis

Blood immunoglobulin G decreased

Lymphocyte count decreased

Back pain

Myalgia

Influenza

Night sweats

Hypocalcaemia

Dry mouth

Acute kidney injury

Oropharyngeal pain

Pain

Pleural effusion

Rash

Clostridium difficile infection

Pancytopenia

Multiple organ dysfunction syndrome

Sepsis

Encephalopathy

Myelodysplastic syndrome

Prostate cancer

Dehydration

Pulmonary embolism

Respiratory failure

Bone marrow failure

Gastrointestinal haemorrhage

Pneumocystis jirovecii pneumonia

Staphylococcal infection

Respiratory tract infection

Infection

Chronic kidney disease

Syncope

Invasive ductal breast carcinoma

Refractory cytopenia with multilineage dysplasia

Tumour associated fever

Metabolic encephalopathy

Somnolence

Pneumonitis

Cardiac arrest

Duodenal ulcer haemorrhage

Haemophagocytic lymphohistiocytosis

Urosepsis

Vaginal infection

Blood bilirubin increased

C-reactive protein increased

Haematemesis

Pancreatitis acute

Hepatic failure

Lymphadenopathy

Atrial fibrillation

Cardio-respiratory arrest

Cardiopulmonary failure

Vertigo

Face oedema

Systemic infection

Myopathy

Large intestinal obstruction

Melaena

Cholecystitis acute

Cardiac failure congestive

Bronchopulmonary aspergillosis

Upper limb fracture

Tumour lysis syndrome

Pulmonary haemorrhage

Atypical pneumonia

Infusion related reaction

Anal fissure

Candida infection

Cerebral toxoplasmosis

Corynebacterium infection

Malignant melanoma

Acute polyneuropathy

Bronchitis

Acute myeloid leukaemia

Cerebral haemorrhage

Cystitis haemorrhagic

Lower respiratory tract infection

Pneumonia aspiration

Liver function test increased

Neuroendocrine carcinoma

Demyelinating polyneuropathy

Status epilepticus

Asphyxia

Escherichia infection

Pseudomonas infection

Hypercalcaemia

Polyarthritis

Tumour haemorrhage

Ischaemic cerebral infarction

Mental status changes

Urinary tract obstruction

Deep vein thrombosis

Allergic bronchitis

Pharyngeal haemorrhage

100%

80%

60%

40%

20%

Study treatment Arm

Tisagenlecleucel - All Patients

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

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

~370

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.