What side effects are associated with this type of intervention?

CAR T-cell therapies for Mantle Cell Lymphoma, such as brexucabtagene autoleucel, are associated with serious and potentially life-threatening toxicities, including cytokine release syndrome, severe cytopenias, and infections. Other common treatments like bendamustine combined with rituximab can cause cytopenias, infections, and gastrointestinal symptoms. Bortezomib, often used in combination with rituximab and dexamethasone, can lead to peripheral neuropathy, thrombocytopenia, and gastrointestinal issues. These side effects highlight the need for careful monitoring and supportive care during treatment.

What prior FDA approvals exist?

For the treatment of Mantle Cell Lymphoma (MCL), the FDA has approved several therapies, including CAR-T cell therapy. Brexucabtagene autoleucel (formerly KTE-X19) is an anti-CD19 CAR-T cell therapy that has shown durable remissions in patients with relapsed or refractory MCL. This therapy involves engineering a patient's T-cells to target and kill cancer cells, similar to the CMV-specific CD19-CAR T-cells being studied. Additionally, while not specifically mentioned in the context, immune-stimulating treatments like the CMV-MVA triplex vaccine are conceptually similar to other immunotherapies that aim to enhance the body's immune response to cancer.

What other types of research exist?

A promising novel alternative for Mantle Cell Lymphoma patients is brexucabtagene autoleucel (KTE-X19), a CAR-T cell therapy targeting CD19. It has shown high overall response rates (93%) and complete response rates (67%) in clinical trials for relapsed or refractory MCL. This therapy offers durable remissions and is a significant advancement in the treatment of MCL.

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CAR T-cell Therapy

CAR T-Cells + CMV Vaccine for Non-Hodgkin's Lymphoma

Phase 1

Recruiting

Led By Alex Herrera

Research Sponsored by City of Hope Medical Center

Eligibility Criteria Checklist

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

Must have

Women of childbearing potential (WOCBP): negative urine or serum pregnancy test

Absolute neutrophil count >= 1000/uL (Transfusions and growth factors must not be used to meet this requirement at initial screening)

Must not have

Clinically significant uncontrolled illness

Prior autologous/allogeneic stem cell transplant

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 15 years

Awards & highlights

No Placebo-Only Group

Summary

This trial studies the safety of using modified immune cells (CAR T-cells) and a special vaccine in patients with certain types of non-Hodgkin lymphoma who haven't responded well to initial treatments. The goal is to enhance the immune system to better target and kill cancer cells, potentially preventing the cancer from coming back. CAR T-cell therapy has shown promising results in treating blood cancers, including non-Hodgkin lymphoma.

Who is the study for?

Adults over 18 with certain types of B-cell non-Hodgkin lymphoma, who are in first relapse or didn't respond to initial treatment. They must be CMV positive, have a good performance status (able to carry out daily activities), and proper organ function. Pregnant women, those with prior stem cell transplants, autoimmune diseases needing steroids, other active cancers or infections can't join.

What is being tested?

The trial is testing genetically modified T-cells targeting CD19 on cancer cells plus a CMV vaccine after stem cell transplantation. The aim is to see if this combination helps prevent the return of high-grade B-cell non-Hodgkin lymphoma after transplant.

What are the potential side effects?

Possible side effects include reactions at the infusion site, flu-like symptoms from the vaccine, increased risk of infection due to immune system modification and potential complications from stem cell transplantation.

Eligibility Criteria

Inclusion Criteria

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

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I am a woman who can have children and my pregnancy test is negative.

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My white blood cell count is healthy without medical help.

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My hemoglobin level is at least 8 g/dl without transfusions or growth factors.

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My kidney function is within the required range and I am not on dialysis.

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I have B cell NHL and am in my first relapse or didn't achieve complete remission after first treatment.

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My platelet count is high enough without transfusions or growth factors.

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My white blood cell count is high enough without medical help.

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I am capable of having children and have not been surgically sterilized.

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My hemoglobin level is at least 8 g/dl without transfusions or growth factors.

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My kidney function is within the required range and I am not on dialysis.

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I am 18 years old or older.

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I have B cell NHL in first relapse and may need a stem cell transplant.

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I am able to care for myself but may not be able to do active work.

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My cancer is confirmed to be a type of CD19+ malignancy.

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I am 18 years old or older.

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I am able to care for myself but may not be able to do active work.

Exclusion Criteria

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

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I do not have any uncontrolled serious illnesses.

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I have had a stem cell transplant using my own or a donor's cells.

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I have a bleeding disorder like von Willebrand's disease or hemophilia.

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I am HIV positive.

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I am currently taking antibiotics for an infection.

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I do not have an active autoimmune disease that needs systemic treatment.

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I am not currently on any experimental treatments or undergoing chemotherapy, biological therapy, or radiation.

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I am not pregnant or breastfeeding.

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I don't have any conditions that would prevent me from undergoing a stem cell transplant.

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I have active viral hepatitis.

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I haven't received growth factors in the last 14 days.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 15 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 15 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 15 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Incidence of adverse events

Secondary study objectives

Achievement of proposed 10×10^6 cytomegalovirus (CMV)-specific CD19-chimeric antigen receptor (CAR) T cells per product and meeting product release requirements for enrolled participants

Clinically significant CMV reactivation

Overall survival (OS)

+2 more

Side effects data

From 2022 Phase 3 trial • 665 Patients • NCT00567567

84%

58300-Neutrophil count decreased

70%

65800-Platelet count decreased

20%

43100-Hypokalemia

18%

44800-Infections and infestations - Other specify

18%

33300-Febrile neutropenia

17%

88500-White blood cell decreased

13%

13200-Anemia

55600-Mucositis oral

42700-Hypocalcemia

13500-Anorexia

11600-Alanine aminotransferase increased

41400-Hyperglycemia

15000-Aspartate aminotransferase increased

43300-Hyponatremia

73700-Sepsis

53700-Lymphocyte count decreased

25700-Diarrhea

65900-Pleural effusion

57600-Nausea

37500-GGT increased

41600-Hyperkalemia

10300-Abdominal pain

20500-Catheter related infection

59700-Oral pain

38900-Hearing impaired

43900-Hypoxia

17200-Blood and lymphatic system disorders - Other specify

14900-Ascites

75700-Small intestinal obstruction

87900-Vomiting

43600-Hypotension

34000-Fibrinogen decreased

23000-Confusion

42600-Hypoalbuminemia

45800-INR increased

69700-Rash maculo-papular

71500-Respiratory failure

73900-Serum amylase increased

26600-Duodenal obstruction

66300-Pneumonitis

58000-Neoplasms benign malignant and unspecified (incl cysts and polyps) - Other specify

56600-Myelitis

75600-Small intestinal mucositis

66800-Postoperative hemorrhage

43500-Hypophosphatemia

37300-Generalized muscle weakness

81200-Treatment related secondary malignancy

31200-Esophagitis

83100-Urinary tract infection

24100-Creatinine increased

11100-Acute kidney injury

62600-Pelvic pain

65300-Pharyngolaryngeal pain

31900-Eye disorders - Other specify

10900-Activated partial thromboplastin time prolonged

11800-Alkaline phosphatase increased

42500-Hyperuricemia

17400-Blood bilirubin increased

63100-Pericardial effusion

72700-Right ventricular dysfunction

37200-General disorders and administration site conditions - Other specify

40000-Hepatic failure

88200-Weight gain

41300-Hypercalcemia

54900-Metabolism and nutrition disorders - Other specify

71000-Renal and urinary disorders - Other specify

69000-Pulmonary hypertension

20100-Cardiac disorders - Other specify

22100-Colitis

44200-Ileal obstruction

81900-Typhlitis

33900-Fever

35500-Gallbladder pain

40600-Hepatobiliary disorders - Other specify

66500-Portal hypertension

12000-Allergic reaction

13100-Anaphylaxis

44700-Immune system disorders - Other specify

13400-Anorectal infection

25600-Device related infection

29500-Enterocolitis infectious

53100-Lung infection

62500-Pelvic infection

75200-Skin infection

82300-Upper respiratory infection

14500-Arterial injury

15300-Ataxia

38800-Headache

63900-Peripheral motor neuropathy

11300-Adult respiratory distress syndrome

29700-Epistaxis

78100-Stridor

68400-Pruritus

51700-Left ventricular systolic dysfunction

27800-Dyspnea

58100-Nervous system disorders - Other specify

29000-Encephalopathy

42100-Hypertension

24700-Dehydration

43200-Hypomagnesemia

31800-Extrapyramidal disorder

52600-Lipase increased

10700-Acidosis

100%

80%

60%

40%

20%

Study treatment Arm

Tandem HST (CEM), Randomly Assigned

Single HST (CEM)

Not Assigned

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: Treatment (CMV-specific CD19-CAR T cells, triplex vaccine)Experimental Treatment4 Interventions

CONDITIONING REGIMEN: Patients receive standard conditioning regimen (typically carmustine, etoposide, cytarabine, melphalan) beginning approximately on day -9 in the absence of disease progression or unacceptable toxicity. TRANSPLANTATION: Patients undergo autoHSCT on day -2. CAR T-CELLS AND VACCINATION: Patients receive CMV-specific CD19-CAR T cells IV on day 0 and CMV-MVA triplex vaccine IM on days 28 and 56 in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Autologous Hematopoietic Stem Cell Transplantation

2017

Completed Phase 3

~2090

0 / 27Eligibility 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

Mantle Cell Lymphoma (MCL) treatments often include CAR T-cell therapy and immunotherapy. CAR T-cell therapy, such as brexucabtagene autoleucel, involves engineering a patient's T-cells to express a chimeric antigen receptor (CAR) that targets CD19 on cancer cells, leading to their destruction. This approach is significant for MCL patients as it offers a targeted attack on cancer cells, potentially leading to durable remissions. Immunotherapies, like the CMV-MVA triplex vaccine, stimulate the immune system to recognize and attack cancer cells. This is crucial for MCL patients because it enhances the body's natural ability to fight the lymphoma, potentially preventing relapse and improving outcomes.

Clinical data, limitations and perspectives on chimeric antigen receptor T-cell therapy in multiple myeloma.