ATLCAR.CD30 cells for Lymphoproliferative Disorders

Phase-Based Estimates
1
Effectiveness
1
Safety
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill, NC
+8 More
ATLCAR.CD30 cells - Biological
Eligibility
Any Age
All Sexes
Eligible conditions
Lymphoproliferative Disorders

Study Summary

Study of CD30 CAR for Relapsed/Refractory CD30+ HL and CD30+ NHL

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Eligible Conditions

  • Lymphoproliferative Disorders
  • Cancer
  • Immunoproliferative Disorders
  • Neoplasms by Histologic Type
  • Lymphatism
  • Immune System Diseases
  • Lymphoma, Diffuse
  • Disease
  • Lymphoma
  • Neoplasms
  • Lymphatic Diseases
  • Lymphoma, Non-Hodgkin

Treatment Effectiveness

Effectiveness Estimate

1 of 3

Study Objectives

This trial is evaluating whether ATLCAR.CD30 cells will improve 3 primary outcomes and 16 secondary outcomes in patients with Lymphoproliferative Disorders. Measurement will happen over the course of 6 weeks.

15 years
Duration of response after administration of CAR.CD30 transduced ATL following lymphodepletion with bendamustine and fludarabine in adult and pediatric patients with CD30+ relapsed/refractory HL and NHL.
Duration of response after administration of CAR.CD30 transduced ATL following lymphodepletion with bendamustine in adult patients with CD30+ relapsed/refractory HL and NHL.
Measure patient reported quality of life using the PROMIS Physical Function (PROMIS Physical Function SF20a) at baseline and over time in adult patients treated with CAR.CD30 T cells.
Measure patient-reported quality of life using the PROMIS Global Health (PROMIS GHS SF v1.0-1.1) at baseline and over time in adult patients treated with CAR.CD30 T cells.
Measure patient-reported symptoms using selected symptom items from the NCI Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) at baseline and over time in adult patients treated with CAR.CD30 T cells.
Survival of ATLCAR.CD30 in vivo when infused after lymphodepletion with bendamustine.
To measure the survival of ATLCAR.CD30 in vivo when infused after lymphodepletion with bendamustine and fludarabine.
2 years
2 year overall survival (OS) after administration of ATLCAR.CD30 transduced ATl following lymphodepletion with bendamustine in adult patients with CD30+ refractory/relapsed HL and NHL
2 year overall survival (OS) after administration of CAR.CD30 transduced ATL following lymphodepletion with bendamustine and fludarabine in adult and pediatric patients with CD30+ relapsed/refractory HL and NHL.
2 year progression free survival (PFS) after administration of ATLCAR.CD30 in combined adult/pediatric patients with CD30+ refractory/relapsed HL and NHL.
2 year progression free survival after administration of ATLCAR.CD30 following lymphodepletion with bendamustine and fludarabine in adult and pediatric patients with CD30+ refractory/relapsed HL and NHL.
2 year progression free survival after administration of ATLCAR.CD30 following lymphodepletion with bendamustine in adult patients with CD30+ in adult patients with CD30+ refractory/relapsed HL and NHL.
6 weeks
Adverse events associated with CAR.CD30 transduced ATL when administered in adult and pediatric patients with CD30+ relapsed/refractory HL and NHL.
Number of adverse events as a measure of safety and tolerability of bendamustine and fludarabine as lymphodepleting agents prior to infusion of CAR.CD30 transduced ATLs in pediatric patients.
Number of participants with adverse events as a measure of safety and tolerability of ATLCAR.CD30 cells to establish a safe dose after lymphodepletion after lymphodepletion with bendamustine and fludarabine in pediatric patients
Number of participants with adverse events as a measure of safety and tolerability of ATLCAR.CD30 cells to establish a safe dose after lymphodepletion with bendamustine in adult patients
Number of participants with adverse events as a measure of safety and tolerability of bendamustine and fludarabine as lymphodepleting agents
Objective response rate as defined by the Lugano Classification for CAR.CD30 transduced ATL following lymphodepletion with bendamustine when administered in adult patients with CD30+ relapsed/refractory HL and NHL
Objective response rate as defined by the Lugano classification for CAR.CD30 transduced ATL following lymphodepletion with bendamustine and fludarabine when administered in adult and pediatric patients with CD30+ relapsed/refractory HL and NHL.

Trial Safety

Trial Design

2 Treatment Groups

Control
ATLCAR.CD30 cells

This trial requires 40 total participants across 2 different treatment groups

This trial involves 2 different treatments. ATLCAR.CD30 Cells is the primary treatment being studied. Participants will all receive the same treatment. There is no placebo group. The treatments being tested are in Phase 1 & 2 and have already been tested with other people.

ATLCAR.CD30 cells
Biological
Phase Ib: In adults, and separately, in children, two doses will be investigated 1x10^8 cells/m2 and 2x10^8 cells/m^2. The study team will run two independent dose-escalation sequences, one for adults and another one for children. The study team plans to use the 3+3 design and start with a low dose of 1x10^8 cells/m2. If there are no DLT in first 3 patients, the study team will go up to the dose of 2 x 10^8 cells/m2. If there is toxicity in 1/3 patients in the initial cohort, the study team would expand to enroll up to 6 patients. If there are dose limiting toxicities (DLT) at the dose of 2 x 10^8 cells/m^2, the study team will initially decrease the dose to an intermediate dose of 1.5 x 10^8 cells/m^. Phase II: The study team planning to enroll 31 patients to contribute data. Sequential boundary will be used to monitor DLT rate.
ControlNo treatment in the control group

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: 15 years
This trial has the following approximate timeline: 3 weeks for initial screening, variable treatment timelines, and roughly 15 years for reporting.

Closest Location

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill - Chapel Hill, NC

Eligibility Criteria

This trial is for patients born any sex of any age. You must have received 1 prior treatment for Lymphoproliferative Disorders or one of the other 8 conditions listed above. There are 10 eligibility criteria to participate in this trial as listed below.

Mark “yes” if the following statements are true for you:
Karnofsky or Lansky score of >60% (Karnofsky for ≥16 years old and Lansky for <16 years old)
Hemoglobin ≥ 8.0 g/dL (transfusion independent for 2 weeks prior to enrollment)
Total bilirubin ≤ 1.5 × ULN, unless attributed to Gilbert's Syndrome
AST ≤ 3 × ULN
Serum creatinine ≤ 1.5 × ULN
Inclusion Criteria Prior to Cell Procurement
Informed consent explained to, understood by and signed by the subject or legal guardian for pediatric subjects; subject and/or legal guradian given a copy of informed consent form for procurement
Ages 3 to 17 years of age for pediatric subjects (weight must be ≥10kg), and for adults ages ≥18 years of age
Diagnosis of recurrent HL or NHL in subjects who have failed >2 prior treatment regimens. Subjects relapsed after autologous or allogeneic stem cell transplant are eligible for this study.
CD30+ disease (result can be pending at the time of cell procurement, but must be confirmed prior to treatment with ATLCAR.CD30 cells). NOTE: CD30+ disease requires documented CD30 expression by immunohistochemistry based on the institutional hematopathology standard.

Patient Q&A Section

Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

What causes lymphoproliferative disorders?

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The cause of lymphoproliferative diseases is still not clear. It was usually thought that cancer originated in a certain organ, but evidence shows that cancer may arise in many organs. It is likely that many different factors, including environmental factors, predispose a person to developing the diseases. Tissue damage may also be a precipitating factor. The overall aim of diagnostic and therapeutic efforts should be to make the disease less likely to occur.

Unverified Answer

How many people get lymphoproliferative disorders a year in the United States?

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About 10,000 children and 7,000 adults were diagnosed with lymphoproliferative disorders in the United States in 2001. The most common disorders are non-Hodgkin's lymphomas and Mature B-Cell Lymphomas. There is no significant difference in diagnostic age groups at diagnosis, although diagnosis rates increased from 1995 to 2001 in children with non-Hodgkin's and mantle cell lymphomas. The five year OS rate was 77% for the pediatric group and 73% for the adult group. Survival for NHLs was comparable between pediatric and adult patients.

Unverified Answer

What are common treatments for lymphoproliferative disorders?

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It is difficult to formulate a one-word answer to the myriad of potential treatment regimens for lymphoproliferative disorders. Treatment involves the combination of agents that are effective in treating each individual condition, and a combination of treatments that are effective against systemic relapse. The agents most often used include chemotherapy, radiotherapy and biologic therapy. The most common first-line treatment is R-CHOP, followed by EBRT and then chemotherapy alone. For patients with high-risk conditions (e.g., bone marrow, central nervous system involvement, liver lesions, or pulmonary disease), treatment with allopurinol or azathioprine/IMiC are often used in combination with chemotherapy.

Unverified Answer

What are the signs of lymphoproliferative disorders?

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The signs of lymphoproliferative disorders include symptoms of lymphadenopathy; enlarged, tender and painful lymph nodes in the neck or under the arm (a finding referred to as 'Barr-Lees-Engelberg nodes'); high levels of the white blood cell count (thrombocytosis) and an elevated gamma glutamyl transpeptidase (GGT), an enzyme produced in the liver that can be elevated in many conditions. B symptoms, including fever, night sweats, loss of appetite and weight loss, can also be present.

Unverified Answer

Can lymphoproliferative disorders be cured?

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Lymphoproliferative disorders can be cured only if the lymphoproliferative disorder is a clonal LPD, as shown by histology, with no recurrences for several years and no metastases at presentation.

Unverified Answer

What is lymphoproliferative disorders?

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Nodal disease is not a rare occurrence in both Hodgkin's disease and anaplastic large cell lymphomas. Clinically, these disorders, especially Hodgkin's disease and ALCL, behave very differently, and their management differs considerably. Nodal staging may help diagnose both diseases early.

Unverified Answer

How does atlcar.cd30 cells work?

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Results from a recent clinical trial provides novel evidence to suggest an unexpected benefit of CD30-directed cell therapy for HL/CLL patients. At a time where effective treatments are scarce, this novel approach holds a great potential for translational application against CD30-overexpressing B-cell neoplasms.

Unverified Answer

Is atlcar.cd30 cells safe for people?

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The data in this report support current recommendations to use CD30-positive cells for allogeneic stem cell transplantation due to safety, in the absence of evidence of harm.

Unverified Answer

What is atlcar.cd30 cells?

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Atlcell CD30 (CD30) cells are a distinct subset of primary CD30+ HL cells with multiple translocations in the t(11;14)(q13;q32). Atlcell CD30 cells are in part HL-like; however, they have other characteristics that set them apart from HL, including cell division in a lytic manner and a more aggressive gene expression profile. Findings from a recent study are important as they raise the possibility of a novel and distinct disorder.

Unverified Answer

Who should consider clinical trials for lymphoproliferative disorders?

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Although some patients with lymphoproliferative disorders, such as T-cell (mycosis fungoides) and B-cell (lymphoma) cancers and ALK-rearranged non-small cell lung cancer, may be eligible for clinical trials, the clinical usefulness of these studies is debated. Future research evaluating the inclusion and exclusion criteria may assist clinicians in managing these patients.

Unverified Answer

What is the primary cause of lymphoproliferative disorders?

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The primary cause of lymphoproliferative disorders is unknown. Because both the diagnosis and characterization of lymphoproliferative disorders are complicated, there are difficulties in developing efficient diagnostic strategies for lymphoproliferative disorders.

Unverified Answer

Does atlcar.cd30 cells improve quality of life for those with lymphoproliferative disorders?

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Patients with ATLC and CD30+PCL+NHL have significant QOL abnormalities. A treatment effect for ATLC and CD30+PCL+NHL, compared with untreated patients, was not demonstrated. However, we did observe a statistically significant improvement in patients with CD30+PCL+NHL, suggesting the possibility of benefit (p = 0.08) for a subset of patients, as has also been documented for ATLC. Based on our results, additional, prospective trials would be preferable.

Unverified Answer
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