What side effects are associated with this type of intervention?

Common treatments for leukemia, including allogeneic hematopoietic cell transplantation (HCT) with ex-vivo T cell receptor Alpha/Beta+ and CD19 depletion, aim to reduce the risk of graft-versus-host disease (GvHD). However, these treatments can still cause significant side effects. These include acute and chronic GvHD, infections due to immunosuppression, and organ toxicities affecting the liver, lungs, and gastrointestinal tract. Chemotherapy, often used in conjunction with HCT, can lead to nausea, vomiting, hair loss, and increased risk of infections. Targeted therapies may cause side effects such as fatigue, diarrhea, and liver dysfunction. Despite these risks, these treatments can improve survival and quality of life for patients with leukemia.

What prior FDA approvals exist?

The FDA has approved several treatments for leukemia that involve targeting specific cells to reduce complications such as graft versus host disease (GvHD). One notable example is the use of CAR-T cell therapies, such as brexucabtagene autoleucel (KTE-X19), which targets CD19 on B cells and has shown efficacy in relapsed or refractory mantle cell lymphoma, a type of non-Hodgkin lymphoma. These therapies involve modifying a patient's T cells to better target and destroy cancerous B cells, similar to the ex-vivo T cell receptor Alpha/Beta+ and CD19 depletion approach being studied to reduce GvHD risk by removing specific T cells and B cells.

What other types of research exist?

Promising novel alternatives for reducing the risk of GvHD in leukemia patients include: 1) Chimeric Antigen Receptor (CAR) T-cell therapy, which uses genetically modified T cells to target and kill cancer cells; 2) Post-transplant cyclophosphamide, which is used to selectively deplete alloreactive T cells post-transplant; 3) T-cell receptor (TCR) engineered T cells, which are designed to target specific antigens on leukemia cells; and 4) Regulatory T cell (Treg) therapy, which involves the infusion of Tregs to modulate the immune response and reduce GvHD. These therapies are being actively researched and show potential for improving outcomes in leukemia patients.

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Cell Therapy

Stem Cell Transplant for Leukemia (HAPLOTAB Trial)

Q: What is the mechanism of action of this treatment?

Common treatments for leukemia include allogeneic hematopoietic cell transplantation (HCT), CAR T-cell therapy, and targeted agents such as BTK inhibitors and BCL2 inhibitors. Allogeneic HCT involves transplanting healthy donor stem cells to replace the patient's diseased bone marrow, leveraging the graft-versus-leukemia (GVL) effect to eradicate cancer cells. CAR T-cell therapy modifies a patient's T-cells to target and destroy leukemia cells, offering a personalized approach. BTK inhibitors (e.g., ibrutinib) and BCL2 inhibitors (e.g., venetoclax) disrupt key survival pathways in leukemia cells, leading to their death. The trial involving ex-vivo T cell receptor Alpha/Beta+ and CD19 depletion aims to reduce GvHD by removing specific T cells and B cells, thus minimizing immune complications and improving patient outcomes. These mechanisms are crucial as they offer targeted, effective treatments while reducing the risk of severe side effects, enhancing the quality of life and survival rates for leukemia patients.

N/A

Recruiting

Led By Erin Morales, MD

Research Sponsored by Baylor College of Medicine

Eligibility Criteria Checklist

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

Must have

Lack of suitable conventional donor (10/10 HLA matched related or unrelated donor) or presence of rapidly progressive disease not permitting time to identify an HLA-matched unrelated donor (excluding cord blood unit availability)

Lansky/Karnofsky score > 50

Must not have

Symptomatic cardiac disease or left ventricular shortening fraction less than 25% or ejection fraction < 40%

Serious concurrent uncontrolled medical disorder or mental illness

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to one year post-hct

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a special stem cell transplant for patients with serious conditions. It removes harmful immune cells from the donor's blood to lower the risk of complications, potentially reducing the need for strong medications afterward.

Who is the study for?

This trial is for patients without a fully matched donor or with rapidly progressing diseases who need a stem cell transplant. It's open to those with certain blood cancers, hemoglobin disorders like thalassemia or sickle cell disease, severe viral infections, immune deficiencies, and bone marrow failures. Participants must be in good enough health to undergo the procedure.

What is being tested?

The study tests a new way of doing transplants using half-matched family donors' blood cells treated to reduce GvHD risk. The treatment uses CliniMACS® TCRα/β-Biotin System to remove specific immune cells that could cause complications post-transplant.

What are the potential side effects?

Potential side effects may include reactions related to the transplantation process such as infection risks due to weakened immunity, graft failure, mild-to-severe GvHD despite preventive measures taken during the procedure, and possible infusion-related reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I don't have a perfect match donor or my disease is progressing too quickly to wait for one.

Select...

I am mostly active and can do things for myself.

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I have a serious blood disorder or bone marrow failure.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My heart is weak, with an ejection fraction below 40%.

Select...

I do not have any serious uncontrolled health or mental conditions.

Select...

I am currently on immunosuppressive drugs for GVHD from a past transplant.

Select...

I am currently living with HIV.

Select...

My kidney function is severely reduced.

Select...

My liver tests are significantly higher than normal.

Select...

I do not have an active infection that would prevent me from receiving strong chemotherapy or a transplant.

Select...

I have severe lung disease with very low lung function.

Select...

I am currently pregnant or breastfeeding.

Select...

I have severe graft versus host disease from a past transplant.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to two years post hct

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to two years post hct

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to two years post hct for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Rate of acute graft versus host disease (GvHD) by grades

Rate of neutrophil engraftment

Rate of platelet engraftment

Secondary study objectives

Overall survival (OS)

Rate of transplant-related mortality (TRM)

The rate of chronic graft versus host disease

Side effects data

From 2020 Phase 3 trial • 324 Patients • NCT00703820

68%

Febrile neutropenia (fever of unknown origin: not clinically or microbiologically documented)

53%

Infection (documented clinically or microbioogically) with Grade 3 or 4 neutrophils (ANC<1.0x10e9/L)

34%

Potassium, serum-low (hypokalemia)

25%

ALT, SGPT (serum glutamic pyruvic transaminase)

16%

Colitis, infectious (e.g., Clostridium difficile)

15%

Infection (documented clinically or microbiologically documented, ANC<1.0x10e9/L, fever>38.5C),blood

15%

AST, SGOT (serum glutamic oxaloacetic transaminase)

13%

Phosphate, serum-low (hypophosphatemia)

12%

Glucose, serum-high (hyperglycemia)

12%

Calcium, serum-low (hypocalcemia)

Hypoxia

Hypertension

Anorexia

Allergic reaction/hypersensitivity (including drug fever)

Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0x10e9/L)

Nausea

Hypotension

Sodium, serum-low (hyponatremia)

Allbumin, serum-low (hypoalbuminemia)

Bilirubin (hyperbilirubinemia)

Tumor lysis syndrome

Diarrhea

Vomiting

Colitis

Infection with normal ANC or Grade 1 or 2 neutrophils

Rash/desquamation

Typhlitis (cecal inflammation)

Pain, rectum

Mucositis/stomatitis (clinical exam), oral cavity

Speech impairment (e.g., dysphasia or aphasia)

Mucositis/stomatitis (functional/symptomatic), oral cavity

Acidosis (metabolic or respiratory)

Sodium, serum-high (hypernatremia)

Pain, Abdomen NOS

Pain, head/headache

Ataxia (incoordination)

Infection with unknown ANC, blood

Cholecystitis

Gastritis (including bile reflux gastritis)

Injection site reaction/extravasation changes

Weight loss

Renal failure

Prolonged QTc interval

Pericardial effusion (non-malignant)

Metabolic/Laboratory

PTT (Partial Thromboplastin Time)

Alkalosis (metabolic or respiratory)

GGT (gamma-Glutamyl transpeptidase)

Potassium, serum-ghigh (hyperkalemia)

Uric acid, serum-high (hyperuricemia)

Magnesium, serum-low (hypomagnesemia)

Ileus, GI (functional obstruction of bowel, i.e., neuroconstipation)

Enteritis (inflammation of the small bowel)

Esophagitis

Syncope (fainting)

Neuropathy: motor

Hemorrhage, pulmonary/upper respiratory, nose

Left ventricular systolic dysfunction

Thrombosis/thrombus/embolism

Hematoma

Confusion

Dysphagia (difficulty swallowing)

Encephalopathy

Infection - other

Adult Respiratory Distress Syndrome (ARDS)

Pneumonitis/pulmonary infiltrates

CNS cerebrovascular ischemia

Pulmonary/upper respiratory - other

Left ventricular diastolic dysfunction

Supraventricular and nodal arrhythmia, sinus bradycardia

Hemorrhage, GI, Lower GI NOS

Vision-photophobia

Death not associated with CTCAE term, sudden death

Right ventricular dysfunction (cor pulmonale)

Tinnitus

Death not associated with CTCAE term, multi-organ failure

Fibrinogen

Pain - other

Perforation, GI, appendix

Constitutional symptoms - other

Lipase

Magnesium, serum-high (hypermagnesemia)

Calcium, serum-high (hypercalcemia)

Hemorrhage, GI, Oral cavity

Gastrointestinal - Other

Distension/bloating, abdominal

Seizure

Somnolence/depressed level of consciousness

Neurology - other

Neuropathy: cranial, CN IX Motor-pharynx; sensory-ear, pharynx, tongue

Infection with unknown ANC, urinary tract NOS

Infection with unknown ANC, catheter-related

DIC (disseminated intravascular coagulation)

Neutrophils/granulocytes (ANC/AGC)

Ocular surface disease

Keratitis (corneal inflammation/corneal ulceration)

Dyspnea (shortness of breath)

Pleural effusion (non-malignant)

Hemorrhage, pulmonary/upper respiratory, bronchopulmonary NOS

Apnea

Valvular heart disease

Supraventricular and nodal arrhythmia, sinus tachycardia

Rash: acne/acneiform

Pruritus/itching

Acute vascular leak syndrome

Pain, back

Urinary frequency/urgency

Mood alteration, euphoria

Pain, vagina

Pain, extremity-limb

INR (International Normalized Ratio of prothrombin time)

Pain, dental/teeth/peridontal

Pain, stomach

Mucotitis/stomatitis (functional/symptomatic), esophagus

Pain, lip

Neuropathy: sensory

Hemorrhage, CNS

Hemorrhage, GU, iuterus

Dehydration

Amylase

Creatinine

CNS necrosis/cystic progression

100%

80%

60%

40%

20%

Study treatment Arm

Cytarabine+Daunorubicin+Etoposide

Clofarabine+Cytarabine

Stem Cell Donors

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: Alpha beta+ T cell depleted CD34+ stem cellsExperimental Treatment1 Intervention

The patient will be receiving a donor stem cell transplant with a preceding conditioning regimen (chemotherapy with, or without, radiation). The investigators will be specially treating the donor's blood cells used for the stem cell transplant.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

CliniMACS

2005

Completed Phase 3

~770

0 / 13Eligibility criteria met

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

Common treatments for leukemia include allogeneic hematopoietic cell transplantation (HCT), CAR T-cell therapy, and targeted agents such as BTK inhibitors and BCL2 inhibitors. Allogeneic HCT involves transplanting healthy donor stem cells to replace the patient's diseased bone marrow, leveraging the graft-versus-leukemia (GVL) effect to eradicate cancer cells. CAR T-cell therapy modifies a patient's T-cells to target and destroy leukemia cells, offering a personalized approach. BTK inhibitors (e.g., ibrutinib) and BCL2 inhibitors (e.g., venetoclax) disrupt key survival pathways in leukemia cells, leading to their death. The trial involving ex-vivo T cell receptor Alpha/Beta+ and CD19 depletion aims to reduce GvHD by removing specific T cells and B cells, thus minimizing immune complications and improving patient outcomes. These mechanisms are crucial as they offer targeted, effective treatments while reducing the risk of severe side effects, enhancing the quality of life and survival rates for leukemia patients.

New Approaches to the Management of Adult Acute Lymphoblastic Leukemia.CD19 chimeric antigen receptor (CD19 CAR)-redirected adoptive T-cell immunotherapy for the treatment of relapsed or refractory B-cell Non-Hodgkin's Lymphomas.Allogeneic Transplantation for Chronic Lymphocytic Leukemia in the Age of Novel Treatment Strategies.