NCT02917083

Brief Summary

The subject has a type of lymph gland cancer called Lymphoma. The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected with germs. Both antibodies and T cells have been used to treat patients with cancers; they both have shown promise, but have not been strong enough to cure most patients. Investigators hope that both will work better together. Investigators have found from previous research that they can put a new gene into T cells that will make them recognize cancer cells and kill them. They now want to test whether these genetically modified T cells given after chemotherapy will be more effective at killing cancer cells. The gene that will be put into the T cells makes an antibody called anti-CD30. This antibody sticks to lymphoma cells because of a substance on the outside of the cells called CD30. Anti-CD30 antibodies have been used to treat people with lymphoma, but have not been strong enough to cure most patients. For this study, the anti-CD30 antibody has been changed so that instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor. These CD30 chimeric receptor-activated T cells (CD30.CAR T cells) seem to kill some of the tumor, but they don't last very long and so their chances of fighting the cancer are unknown. Several studies suggest that the infused T cells need room to be able to multiply and grow to accomplish their functions, and that this may not happen if there are too many other T cells in circulation. Because of that, doctors may use chemotherapy drugs to decrease the level of circulating T cells prior to the CD30.CAR T cells infusion. This is called "lymphodepletion" CD30.CAR T cells have previously been studied in lymphoma patients.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P75+ for phase_1

Timeline
167mo left

Started May 2017

Longer than P75 for phase_1

Geographic Reach
1 country

2 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress40%
May 2017Feb 2040

First Submitted

Initial submission to the registry

September 23, 2016

Completed
5 days until next milestone

First Posted

Study publicly available on registry

September 28, 2016

Completed
7 months until next milestone

Study Start

First participant enrolled

May 8, 2017

Completed
8.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2026

Completed
13.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2040

Expected
Last Updated

July 25, 2025

Status Verified

July 1, 2025

Enrollment Period

8.9 years

First QC Date

September 23, 2016

Last Update Submit

July 22, 2025

Conditions

Keywords

chimeric antigen receptorsimmunotherapyCAR T-cellslymphoma

Outcome Measures

Primary Outcomes (1)

  • Number of Patients with Dose-Limiting Toxicities (DLT)

    Each treated patient will be followed for 6 weeks post the T-cell infusion for the evaluation of DLTs.

    6 weeks

Secondary Outcomes (3)

  • Median Number of T cells transduced with the vector

    15 years

  • Overall Response Rate

    8 weeks

  • Mean Number of T cells transduced with the vector

    15 years

Study Arms (1)

CD30.CAR T Cells

EXPERIMENTAL

Each patient will receive one infusion of CAR modified T cells. Unless post autologous transplant, patients will receive lymphodepleting chemotherapy as three daily doses of cyclophosphamide (Cy: 500mg/m2/day) together with fludarabine (Flu:30mg/m2/day) from 48 hours to 2 weeks before T cell infusion. Clofarabine (20 mg/m2/day) may be substituted for fludarabine.

Genetic: CAR T Cells

Interventions

Three dose levels will be evaluated based on safety data from our current study of CD30 CAR T cells. Cohorts of three to six patients will be enrolled at each dose level. Each patient will receive one infusion of CAR modified T cells according to the following dosing schedule: Dose Level One: 2x10\^7 cells/m2. Dose Level Two: 1x10\^8 cells/m2. Dose Level Three: 2x10\^8 cells/m2.

Also known as: CD30.CAR T Cells
CD30.CAR T Cells

Eligibility Criteria

Age12 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Diagnosis of relapsed/refractory HL or NHL.
  • CD30 positive tumor as assayed in a CLIA certified pathology laboratory (result can be pending at this time)
  • Hgb ≥ 7.0 (may be a transfused value)
  • Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.
  • Karnofsky or Lansky score of \> 60%
  • Diagnosis of relapsed/refractory HL or NHL.
  • CD30-positive tumor as assayed in a CLIA certified pathology laboratory.
  • Age 16 to 75 for the first three patients on a dose level; thereafter, if no DLT, patients aged 12 to 75 can be treated on that dose level.
  • Bilirubin 1.5 times or less than the upper limit of normal.
  • AST 3 times or less than the upper limit of normal.
  • Estimated GFR \> 70 mL/min.
  • Pulse oximetry of \> 90% on room air
  • EKG shows no significant arrhythmias
  • Karnofsky or Lansky score of \> 60%.
  • Available autologous T cells with greater than or equal to 15% expression of CD30CAR determined by flow-cytometry.
  • +4 more criteria

You may not qualify if:

  • Active infection with HIV or HTLV (can be pending at this time).
  • Active bacterial, fungal or viral infection.
  • Currently receiving any investigational agents or received any tumor vaccines within the previous six weeks.
  • Received anti-CD30 antibody-based therapy within the previous 4 weeks.
  • Subjects with rapidly progressive disease, defined as kinetic failure to previous chemotherapy.
  • Bulky disease (defined as a 10 cm or greater mass or mediastinal disease with a transverse diameter exceeding 33% of the transthoracic diameter).
  • History of hypersensitivity reactions to murine protein-containing products.
  • Pregnant or lactating.
  • Tumor in a location where enlargement could cause airway obstruction.
  • Current use of systemic corticosteroids at a dose equivalent to 0.5 mg/kg/day of prednisone or higher.
  • Active hemorrhagic cystitis.
  • Active bacterial, viral or fungal infection.
  • Symptomatic cardiac disease (NYHA Class III or IV disease).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

RECRUITING

Related Publications (1)

  • Ramos CA, Grover NS, Beaven AW, Lulla PD, Wu MF, Ivanova A, Wang T, Shea TC, Rooney CM, Dittus C, Park SI, Gee AP, Eldridge PW, McKay KL, Mehta B, Cheng CJ, Buchanan FB, Grilley BJ, Morrison K, Brenner MK, Serody JS, Dotti G, Heslop HE, Savoldo B. Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma. J Clin Oncol. 2020 Nov 10;38(32):3794-3804. doi: 10.1200/JCO.20.01342. Epub 2020 Jul 23.

MeSH Terms

Conditions

Hodgkin DiseaseLymphoma, Non-HodgkinLymphoma

Interventions

Immunotherapy, Adoptive

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Adoptive TransferImmunization, PassiveImmunizationImmunotherapyImmunomodulationBiological TherapyTherapeuticsImmunologic TechniquesInvestigative Techniques

Study Officials

  • Carlos A Ramos, MD

    Baylor College of Medicine

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Carlos A Ramos, MD

CONTACT

Vicky Torrano, RN

CONTACT

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor

Study Record Dates

First Submitted

September 23, 2016

First Posted

September 28, 2016

Study Start

May 8, 2017

Primary Completion

April 1, 2026

Study Completion (Estimated)

February 1, 2040

Last Updated

July 25, 2025

Record last verified: 2025-07

Data Sharing

IPD Sharing
Will not share

Locations