Treatment of Chemotherapy Refractory Multiple Myeloma by CART-138 (CART-138)

January 26, 2016 updated by: Han weidong, Chinese PLA General Hospital

Clinical Study of Chimeric CD(Cluster of Differentiation)138 Antigen Receptor-modified T Cells in Relapsed and/or Chemotherapy Refractory Multiple Myelomas

RATIONALE: Placing a tumor antigen chimeric receptor that has been created in the laboratory into patient autologous or donor-derived T cells may make the body build immune response to kill cancer cells.

PURPOSE: This clinical trial is to study genetically engineered lymphocyte therapy in treating patients with CD138 positive multiple myeloma that is relapsed (after stem cell transplantation or intensive chemotherapy) or refractory to further chemotherapy.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-CD138 vector (referred to as CART-138 cells).

II. Determine duration of in vivo survival of CART-138 cells. RT-PCR (reverse transcription polymerase chain reaction) analysis of whole blood and bone marrow will be used to detect and quantify survival of CART-138 TCR zeta:CD137 and TCR (T-cell receptor) zeta cells over time.

SECONDARY OBJECTIVES:

I. For patients with detectable disease, measure anti-myeloma response due to CART-138 cell infusions.

II. To determine if the CD137 transgene is superior to the TCR zeta only transgene as measured by the relative engraftment levels of CART-138 TCR zeta:CD137 and TCR zeta cells over time.

III. Estimate relative trafficking of CART-138 cells in bone marrow.

IV. For patients with stored or accessible myeloma cells, determine myeloma cell killing by CART-138 cells in vitro.

V. Determine if cellular or humoral host immunity develops against the murine anti-CD138, and assess correlation with loss of detectable CART-138 (loss of engraftment).

VI. Determine the relative subsets of CART-138 T cells (Tcm, Tem, and Treg).

OUTLINE: Patients are assigned to 1 group according to order of enrollment.

Patients receive anti-CD138-CAR (coupled with CD137 and CD3 zeta signalling domains)vector-transduced autologous T cells on days 0,1, and 2 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed intensively for 6 months, every 3 months for 2 years, and annually thereafter for 13 years.

Study Type

Interventional

Enrollment (Anticipated)

10

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100853
        • Recruiting
        • Chinese PLA General Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Yao Wang, Ph.D
        • Principal Investigator:
          • Quanshun Wang, Ph.D

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male and female subjects with CD138 positive multiple myeloma in patients with no available curative treatment options (such as autologous or allogeneic SCT) who have limited prognosis (several months to < 2 year survival) with currently available therapies will be enrolled.
  • CD138 positive multiple myeloma CR can not be achieved after at least 4 prior combination chemotherapy regimens.
  • MM in CR(complete remission)2 or CR3 and not eligible for allogeneic SCT because of age, comorbid disease, or lack of available family member or unrelated donor.
  • Less than 1 year between last chemotherapy and progression (i.e. most recent progression free interval < 1 year).
  • Relapsed after prior autologous or allogenic SCT. MM patients with relapsed or residual disease after at least 1 prior therapy and not eligible for allogeneic SCT.

  • Residual disease after primary therapy and not eligible for autologous SCT

    • Expected survival > 12 weeks
    • Creatinine < 2.5 mg/dl
    • ALT(alanine aminotransferase)/AST (aspartate aminotransferase)< 3x normal
    • Bilirubin < 2.0 mg/dl
    • Any relapse after prior SCT will make patient eligible regardless of other prior therapy
    • Adequate venous access for apheresis, and no other contraindications for leukapheresis
    • Voluntary informed consent is given

Exclusion Criteria:

  • Pregnant or lactating women
  • The safety of this therapy on unborn children is not known. Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion.
  • Uncontrolled active infection.
  • Active hepatitis B or hepatitis C infection.
  • Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
  • Previously treatment with any gene therapy products
  • Feasibility assessment during screening demonstrates < 30% transduction of target lymphocytes, or insufficient expansion (< 5-fold) in response to CD3/CD137 costimulation.
  • Any uncontrolled active medical disorder that would preclude participation as outlined.
  • HIV infection.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: anti-CD138 CAR T cells
Patients receive anti-CD138-CAR retroviral vector-transduced autologous or donor-derived T cells on days 0,1, 2 in the absence of disease progression or unacceptable toxicity.
Biological: CART-138 cells
Other Names:
  • chimeric antigen receptor T cells with specificity for CD138 genetically modified lymphocyte therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Occurrence of study related adverse events
Time Frame: Until week 24
defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment
Until week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Anti-myeloma responses to CART-138 cell infusions
Time Frame: up to 24 weeks
by measuring the changes of aberrant immunoglobulin in serum and multiple myeloma cells in bone marrow.
up to 24 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
in vivo existence of CART-138
Time Frame: 1 year
measurement of CART-138 cells in peripheral blood by PCR method
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chinese PLA General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2013

Primary Completion (ANTICIPATED)

June 1, 2016

Study Completion (ANTICIPATED)

June 1, 2016

Study Registration Dates

First Submitted

June 24, 2013

First Submitted That Met QC Criteria

June 24, 2013

First Posted (ESTIMATE)

June 26, 2013

Study Record Updates

Last Update Posted (ESTIMATE)

January 28, 2016

Last Update Submitted That Met QC Criteria

January 26, 2016

Last Verified

January 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHN-PLAGH-BT-008

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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