Health TrialsbyHealthPanel

A Phase I Trial Anti-CC Chemokine Receptor 4 Chimeric Antigen Receptor T Cells (CCR4 CAR T Cells) for CCR4 Expressing T-cell Malignancies Including Peripheral T-cell Non-Hodgkin Lymphoma (PTCL) and Cutaneous T-cell Non-Hodgkin Lymphoma (CTCL)

ConditionsRelapsed and/or Refractory Mature T Cell MalignancyPeripheral T-Cell LymphomaAngioimmunoblastic T-cell LymphomaAnaplastic Large Cell LymphomaHepatosplenic T-cell LymphomaMonomorphic Epithelialtropic Intestinal LymphomaEnteropathy Associated T-cell LymphomaCutaneous T-Cell LymphomaMycosis FungoidesSubacute Panniculitis-like T-cell Lymphoma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-120
SponsorNational Cancer Institute (NCI)

About this trial

Background:

Chemokine receptor 4 (CCR4) is a protein that is found on the surface of certain T-cell lymphoma cells and is common in mature T-cell cancers. White blood cells can be changed with molecules called anti-CCR4 to express a chimeric antigen receptors (CAR), which is a molecule that directs a white blood cell to attack other cells. The CAR in this study attacks the CCR4 protein found on your T-cell lymphoma. This type if therapy is called gene therapy. Gene therapy involves a person s own white blood cells modified to target cancer cells. More research is needed to find out if gene therapy can treat T-cell cancers and do it safely.

Objective:

To test safety of giving people with certain mature T-cell lymphomas their own white blood cells modified with anti-CCR-4 CAR.

Eligibility:

People aged 18 and older with certain mature T-cell lymphomas that have not responded to or have come back after treatment. They must have a T-cell lymphoma that has CCR4 on the surface of the cancer cells.

Design:

Participants will be screened. They will have a medical history and physical exam. Tests of blood, urine, and heart and lung function will be done.

Participants will have tests:

Computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging scans: They will lie on a table that slides into a donut-shaped machine or a tube. Pictures of the inside of the body will be taken. Before the PET scan, they will get an injection of radioactive fluid in a vein in the arm. Before the MRI, they may get a contrast dye injected through a vein (IV) in the arm.

A biopsy of the tumor may be taken. A bone marrow sample may be taken from the hip: The area will be numbed and a large needle inserted through the skin.

Leukapheresis will be done to obtain T-cells that will be genetically modified to express anti-CCR4 CARs on T-cells: Blood is drawn through an IV in one arm, circulated through a machine, and then returned through an IV in the other arm.

Chemotherapy drugs will be given in an IV to prepare the body to accept the modified CAR T cells.

The modified cells will be given in an IV.

Participants will be followed for 15 years: This will require blood tests over the first 1-2 years followed by yearly visits and possibly telehealth updates.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Pathologically (biopsy) confirmed histologic diagnosis of a relapsed/refractory CCR4+ mature T-cell malignancy from one of the following subtypes: peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL), hepatosplenic t-cell lymphoma (HSTCL), monomorphic epithelialtropic intestinal lymphoma (MEITL), enteropathy associated T-cell lymphoma (EATL) or cutaneous T-cell lymphoma (CTCL) including mycosis fungoides and subacute panniculitis-like T-cell Lymphoma, or lymphomatous subtypes of ATL without evidence of CNS involvement or substantial circulating disease confirmed by the Laboratory of Pathology, NCI.

Adequate tissue [a formalin fixed tissue block or 15 slides of tumor sample (archival or fresh)] from diagnostic biopsy (archival or fresh) must be available.

Participants with ALCL must have failed at least one prior line of Brentuximab-containing therapy.

Due to the generally indolent nature of the disease, participants with Mycosis Fungoides must have exhausted all standard therapies as determined by the enrolling physician and principal investigator to be eligible for this study.

Disqualifiers

Participants with any current or prior CNS involvement by malignancy are excluded from this study. All potential participants will be screened with brain imaging prior to enrollment on study.

Participants with >1000 atypical cells/mm^3 by peripheral blood flow cytometry at screening.

Participants with a history of serologically or biopsy confirmed autoimmune disorders are excluded from this study. As an exception, participants with EATL whose celiac disease is well controlled and who will maintain a strict gluten-free diet are eligible.

HTLV I/II positive participants with a history of HTLV-associated myelopathy/tropical spastic paraparesis (TSP)

Trial design

Design model

Sequential

Treatments tested in this trial

  • Cyclophosphamide

    Drug

    Days -5 to -3: Cyclophosphamide 300 mg/m\^2 x 3 days

  • Fludarabine

    Drug

    Days -5 to -3: Fludarabine 30 mg/m\^2 IV daily over 30 minutes for 3 days

  • Autologous CCR4 CAR T cells

    Biological/Vaccine

    Day 0: Cells will be infused intravenously (IV) over 10-30 minutes

Treatment groups

60 Participants
are divided into 2 treatment groups
Group A: Arm 1Experimental treatment 3 interventions
Group B: Arm 2Experimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Determine safety profile of administering autologous CCR4 CAR T cells

The number of participants who experience Adverse Events per CTCAE v5.0, by type, grade and frequency of toxicities from time of lymphodepleting regimen through 12 weeks after the last cell infusion.

Time frame
12 weeks

Secondary outcomes

1

To determine the feasibility of manufacturing and delivering the targeted dose level of CCR4 CAR T cells to participants

Feasibility will be defined by the successful manufacturing and expansion of the CCR4 CAR T cells for the first 6 participants to satisfy the targeted dose level and meet the requirements of the COA.

Time frame
1 year
2

Overall survival (OS)

OS will be assessed in each group and reported using the Kaplan-Meier method.

Time frame
After confirmed disease progression or initiation of new anti-cancer therapy, survival assessed every 3-6 months (+/- 28 days) up to 15 years.
3

Duration of response (DOR) and Progression-free survival (PFS)

DOR and PFS will be assessed with radiographic findings and reported using the Kaplan-Meier method.

Time frame
weeks 4, 12, then every 3 months until Month 12, then at Months 18 and 24 then every 6 months until Month 60 then yearly, after cell infusion, until progression or up to 15 years post cell infusion.
4

Complete response rate (CR), Partial response rate (PR) and Overall response rate (ORR=CR+PR)

CR, PR and ORR will be assessed with radiographic findings and reported using the Kaplan-Meier method.

Time frame
Weeks 4, 12, then every 3 months until Month 12, then at Months 18 and 24 after cell infusion.

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov
Apply now