Treatment of Chemotherapy Refractory Multiple Myeloma by CART-138

Last updated: January 26, 2016
Sponsor: Chinese PLA General Hospital
Overall Status: Trial Status Unknown

Phase

1/2

Condition

Multiple Myeloma

Cancer

Leukemia

Treatment

N/A

Clinical Study ID

NCT01886976
CHN-PLAGH-BT-008
  • Ages 18-80
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Male and female subjects with CD138 positive multiple myeloma in patients with noavailable curative treatment options (such as autologous or allogeneic SCT) who havelimited prognosis (several months to < 2 year survival) with currently availabletherapies will be enrolled.

  • CD138 positive multiple myeloma CR can not be achieved after at least 4 priorcombination chemotherapy regimens.

  • MM in CR(complete remission)2 or CR3 and not eligible for allogeneic SCT because ofage, comorbid disease, or lack of available family member or unrelated donor.

  • Less than 1 year between last chemotherapy and progression (i.e. most recentprogression free interval < 1 year).

  • Relapsed after prior autologous or allogenic SCT. MM patients with relapsed orresidual 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 priortherapy

  • Adequate venous access for apheresis, and no other contraindications forleukapheresis

  • Voluntary informed consent is given

Exclusion

Exclusion Criteria:

  • Pregnant or lactating women

  • The safety of this therapy on unborn children is not known. Female study participantsof reproductive potential must have a negative serum or urine pregnancy test performedwithin 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 notexclusionary.

  • Previously treatment with any gene therapy products

  • Feasibility assessment during screening demonstrates < 30% transduction of targetlymphocytes, or insufficient expansion (< 5-fold) in response to CD3/CD137costimulation.

  • Any uncontrolled active medical disorder that would preclude participation asoutlined.

  • HIV infection.

Study Design

Total Participants: 10
Study Start date:
June 01, 2013
Estimated Completion Date:
June 30, 2016

Study 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.

Connect with a study center

  • Chinese PLA General Hospital

    Beijing, Beijing 100853
    China

    Active - Recruiting

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