Administration of T Lymphocytes for Hodgkin's Lymphoma and Non-Hodgkin's Lymphoma (CART CD30)

NCT01316146 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: LCCC 1544-ATLH-27721-CART CD30
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief Summary

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. Antibodies are proteins that protect the body from diseases caused by germs or toxic substances. They work by binding those germs or substances, which stops them from growing and causing bad effects. 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. Investigators now want to see if they can attach a gene to T cells that will help them do a better job at recognizing and killing lymphoma cells. The new gene that investigators will put in 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 seem to kill some of the tumor, but they don't last very long and so their chances of fighting the cancer are unknown.

Conditions

Non-Hodgkin's Lymphoma; Hodgkin's Lymphoma

Keywords

Hodgkin's Lymphoma; Non-Hodgkin's Lymphoma; Lymphoma; T lymphocytes

Outcome Measures

Primary Outcomes (1)

• Number of participants with adverse events as a measure of safety and tolerability of escalating doses of autologous activated T lymphocytes

  To evaluate the safety of escalating doses of autologous activated T lymphocytes (ATL), genetically modified to express an artificial chimeric antigen receptor (CAR) that targets the CD30 molecule (CAR.CD30) and also contains the CD28 endodomain, in patients with CD30+ refractory/relapsed Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL).

  6 weeks

Secondary Outcomes (2)

• Measure the survival of CAR.CD30 in vivo

  15 years

• Measure the response of the subjects tumor to the CAR.CD30 transduced ATL

  15 years

Study Arms (1)

CAR.CD30 T cells

EXPERIMENTAL

Three dose levels will be evaluated. Using the modified continual reassessment method, cohorts of size two will be enrolled at each dose level. Each patient will receive one injection (IV) according to the dosing schedules: starting with the lowest cell dose (2×10\^7 cells/m2) and then escalate the cell dose to the highest cell dose (2×10\^8/m2) as per study design.

Drug: CAR.CD30 T cells

Interventions

CAR.CD30 T cells DRUG

Three dose levels will be evaluated: Group One, 2x10\^7 cells/m\^2 Group Two, 1x10\^8 cells/m\^2 Group Three, 2x10\^8 cells/m\^2; Cell Administration: CAR+ ATL will be given by intravenous injection over 1-10 minutes through either a peripheral or a central line. The expected volume will be 1-50cc.

CAR.CD30 T cells

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Referred patients will initially be consented for procurement of blood for generation of the transduced ATL. Eligibility criteria at this stage include:
• Diagnosis of recurrent CD30+ HL or CD30+ NHL, or newly diagnosed patients unable to receive or complete standard therapy OR diagnosis of relapsed/refractory CD30+ HL or CD30+ NHL with a treatment plan that will include high dose therapy and stem cell transplantation
• CD30 positive tumor (result can be pending at this time)
• Hgb \> 8.0
• Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.
• Karnofsky or Lansky score greater than 60%

You may not qualify if:

• \- Active infection with HIV, HTLV, HBV, HCV (can be pending at this time).
• Diagnosis - CD30+ HL or CD30+ NHL:
• During the Dose Escalation Phase: only adult patients with active disease failing standard therapy
• After Dose Escalation: any patient (children or adults) newly diagnosed, unable to receive or complete standard therapy OR diagnosis of relapsed/refractory CD30+ HL or CD30+ NHL with a treatment plan that will include high dose therapy and autologous stem cell transplantation. (During dose escalation: only adult patients (age 18 and older; After Dose Escalation: any patient (children ages 0-17 or adults)
• CD30 positive tumor
• Bilirubin 1.5 times or less than upper limit of normal.
• AST 3 times or less than upper limit of normal.
• Serum creatinine 1.5 times or less than upper limit of normal.
• Pulse oximetry of \> 90% on room air
• Karnofsky or Lansky score of \> 60%.
• Available autologous T cells with 15% or more expression of CD30CAR determined by flow-cytometry.
• Recovered from acute toxic effects of all prior chemotherapy at least one week and 30 days from prior chemotherapy before entering this study
• Adequate pulmonary function with FEV1, FVC and DLCO greater than or equal to 50% of expected corrected for hemoglobin.
• Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded. The male partner should use a condom.
• Patients or legal guardians must sign an informed consent indicating that they are aware this is a research study and have been told of its possible benefits and toxic side effects. Patients or their guardians will be given a copy of the consent form.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• The Methodist Hospital Research Institute: collaborator
• Baylor College of Medicine: collaborator
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator

Study Sites (3)

University of North Carolina Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Ramos CA, Ballard B, Zhang H, Dakhova O, Gee AP, Mei Z, Bilgi M, Wu MF, Liu H, Grilley B, Bollard CM, Chang BH, Rooney CM, Brenner MK, Heslop HE, Dotti G, Savoldo B. Clinical and immunological responses after CD30-specific chimeric antigen receptor-redirected lymphocytes. J Clin Invest. 2017 Sep 1;127(9):3462-3471. doi: 10.1172/JCI94306. Epub 2017 Aug 14.

  PMID: 28805662 DERIVED

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Hodgkin Disease; Lymphoma

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Barbara Savoldo, MD, PhD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2011
• First Posted: March 16, 2011
• Study Start: October 3, 2011
• Primary Completion: January 28, 2016
• Study Completion: May 4, 2022
• Last Updated: March 22, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)