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

Primary Purpose

Multiple Myeloma

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
CART-138 cells
Sponsored by
Chinese PLA General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring multiple myeloma

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Chinese PLA General HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

anti-CD138 CAR T cells

Arm Description

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.

Outcomes

Primary Outcome Measures

Occurrence of study related adverse events
defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment

Secondary Outcome Measures

Anti-myeloma responses to CART-138 cell infusions
by measuring the changes of aberrant immunoglobulin in serum and multiple myeloma cells in bone marrow.

Full Information

First Posted
June 24, 2013
Last Updated
January 26, 2016
Sponsor
Chinese PLA General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01886976
Brief Title
Treatment of Chemotherapy Refractory Multiple Myeloma by CART-138
Acronym
CART-138
Official Title
Clinical Study of Chimeric CD(Cluster of Differentiation)138 Antigen Receptor-modified T Cells in Relapsed and/or Chemotherapy Refractory Multiple Myelomas
Study Type
Interventional

2. Study Status

Record Verification Date
January 2016
Overall Recruitment Status
Unknown status
Study Start Date
June 2013 (undefined)
Primary Completion Date
June 2016 (Anticipated)
Study Completion Date
June 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese PLA General Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
multiple myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
anti-CD138 CAR T cells
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
CART-138 cells
Other Intervention Name(s)
chimeric antigen receptor T cells with specificity for CD138 genetically modified lymphocyte therapy
Primary Outcome Measure Information:
Title
Occurrence of study related adverse events
Description
defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment
Time Frame
Until week 24
Secondary Outcome Measure Information:
Title
Anti-myeloma responses to CART-138 cell infusions
Description
by measuring the changes of aberrant immunoglobulin in serum and multiple myeloma cells in bone marrow.
Time Frame
up to 24 weeks
Other Pre-specified Outcome Measures:
Title
in vivo existence of CART-138
Description
measurement of CART-138 cells in peripheral blood by PCR method
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Chinese PLA General Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100853
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Weidong Han, Ph.D
Phone
86-10-13651392893
Email
hanwdrsw@sina.com
First Name & Middle Initial & Last Name & Degree
Bo Guo, Ph.D
Phone
86-10-15201186743
Email
drguobo@163.com
First Name & Middle Initial & Last Name & Degree
Yao Wang, Ph.D
First Name & Middle Initial & Last Name & Degree
Quanshun Wang, Ph.D

12. IPD Sharing Statement

Learn more about this trial

Treatment of Chemotherapy Refractory Multiple Myeloma by CART-138

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