Treatment of Chemotherapy Refractory Multiple Myeloma by CART-138

Multiple Myeloma Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01886976
• Other study ID #: CHN-PLAGH-BT-008
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: June 24, 2013
• Last updated: January 26, 2016
• Start date: June 2013
• Est. completion date: June 2016

Study information

• Verified date: January 2016
• Source: Chinese PLA General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Biological:
• CART-138 cells

Locations

Country	Name	City	State
China	Chinese PLA General Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chinese PLA General Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	in vivo existence of CART-138	measurement of CART-138 cells in peripheral blood by PCR method	1 year	Yes
Primary	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	Until week 24	Yes
Secondary	Anti-myeloma responses to CART-138 cell infusions	by measuring the changes of aberrant immunoglobulin in serum and multiple myeloma cells in bone marrow.	up to 24 weeks	Yes