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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT03706547
Other study ID # SHZS-MM002
Secondary ID
Status Not yet recruiting
Phase Phase 1
First received
Last updated
Start date October 30, 2018
Est. completion date December 2021

Study information

Verified date October 2018
Source Shanghai Zhongshan Hospital
Contact Zheng Wei, M.D.
Phone +(86)-21 64041990
Email wei.zheng@zs-hospital.sh.cn
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The goal of this clinical trial is to study the feasibility and efficacy of anti-CD19/BCMA bispecific chimeric antigen receptors (CARs) T cell therapy for relapsed and refractory multiple myeloma.


Description:

Primary Objectives

1. To determine the feasibility ad safety of anti-CD19/BCMA CAR-T cells in treating patients with BCMA-positive multiple myeloma.

Secondary Objectives

1. To access the efficacy of anti-CD19/BCMA CAR-T cells in patients with multiple myeloma.

2. To determine in vivo dynamics and persistency of anti-CD19/BCMA CAR-T cells.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 20
Est. completion date December 2021
Est. primary completion date July 2020
Accepts healthy volunteers No
Gender All
Age group 18 Years to 70 Years
Eligibility Inclusion Criteria:

- Expected survival > 12 weeks

- Diagnosis of Multiple Myeloma by IMWG updated criteria (2014)

- Pathology demonstrated that BCMA-poitive malignant plasma cells exited in bone marrow or plamacytoma

- Exited measurable lesions and in accordance with one of the following test indicators: serum M protein=1 g/dl; urine M protein=200 mg/24h; serum free light chain=10 mg/dl; diagnosis of plasmacytoma by biopsy

- The criteria for relapsed and refractory multiple myeloma: patients previously received at least 3 different prior treatment regimens for multiple myeloma, including protein inhibitors (eg: Bortezomib), and immunomodulator (eg: Revlimid), and have disease progression in the past 60 days

- At least 90 days after stem cell transplantation

- Clinical performance status of ECOG score 0-2

- Creatinine=2.0 mg/dl

- Bilirubin=2.0 mg/dl

- The ALT/AST value is lower than 2.5-fold of normal value

- Accessible to intravenous injection, and no white blood cell collection contraindications

- Sexually active patients must be willing to utilize one of the more effective birth control methods for 30 days after the CTL infusion. Male partner should use a condom

- 5mg/day dose of Prednisone or other equivalent steroid hormone drugs (eg: Dexamethasone) were not used for two weeks before apheresis and CAR-T infusion

- Able to understand and sign the Informed Consent Document.

Exclusion Criteria:

- Patients with symptoms of central nervous system

- Patients with second malignancies in addition to multiple myeloma

- Active hepatitis B or C, HIV infections

- Any other active diseases could affect the enrollment of this trial

- Long term use of immunosuppressive agents after organ transplantation, except currently receiving or recently received glucocorticoid treatment

- Patients with organ failure

- Women of child-bearing potential who are pregnant or breastfeeding during therapy, or have a planned pregnancy with 2 months after therapy

- A history of mental illness and poorly controlled

- Women of child-bearing potential who are not willing to practice birth control from the time of enrollment on this study and for 2 months after receiving the preparative regimen. Women of child bearing potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion

- Patients who are accounted by researchers to be not appropriate for this test

- Subjects suffering disease affects the understanding of informed consent or complying with study protocol

Study Design


Intervention

Biological:
anti-CD19/BCMA CAR-T cells
Retroviral vector-transduced autologous T cells to express anti-CD19 and anti-BCMA CARs
Drug:
Fludarabine
30mg/m2/d
Cyclophosphamide
300mg/m2/d

Locations

Country Name City State
China Department of Hematology ,Fudan University Zhongshan Hospital Shanghai

Sponsors (3)

Lead Sponsor Collaborator
Peng Liu Hrain Biotechnology, Shanghai East Hospital

Country where clinical trial is conducted

China, 

References & Publications (30)

Ali SA, Shi V, Maric I, Wang M, Stroncek DF, Rose JJ, Brudno JN, Stetler-Stevenson M, Feldman SA, Hansen BG, Fellowes VS, Hakim FT, Gress RE, Kochenderfer JN. T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma. Blood. 2016 Sep 29;128(13):1688-700. doi: 10.1182/blood-2016-04-711903. Epub 2016 Jul 13. — View Citation

Bruno B, Rotta M, Patriarca F, Mordini N, Allione B, Carnevale-Schianca F, Giaccone L, Sorasio R, Omedè P, Baldi I, Bringhen S, Massaia M, Aglietta M, Levis A, Gallamini A, Fanin R, Palumbo A, Storb R, Ciccone G, Boccadoro M. A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med. 2007 Mar 15;356(11):1110-20. — View Citation

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Chu J, He S, Deng Y, Zhang J, Peng Y, Hughes T, Yi L, Kwon CH, Wang QE, Devine SM, He X, Bai XF, Hofmeister CC, Yu J. Genetic modification of T cells redirected toward CS1 enhances eradication of myeloma cells. Clin Cancer Res. 2014 Aug 1;20(15):3989-4000. doi: 10.1158/1078-0432.CCR-13-2510. Epub 2014 Mar 27. — View Citation

Drent E, Groen RW, Noort WA, Themeli M, Lammerts van Bueren JJ, Parren PW, Kuball J, Sebestyen Z, Yuan H, de Bruijn J, van de Donk NW, Martens AC, Lokhorst HM, Mutis T. Pre-clinical evaluation of CD38 chimeric antigen receptor engineered T cells for the treatment of multiple myeloma. Haematologica. 2016 May;101(5):616-25. doi: 10.3324/haematol.2015.137620. Epub 2016 Feb 8. — View Citation

Drent E, Themeli M, Poels R, de Jong-Korlaar R, Yuan H, de Bruijn J, Martens ACM, Zweegman S, van de Donk NWCJ, Groen RWJ, Lokhorst HM, Mutis T. A Rational Strategy for Reducing On-Target Off-Tumor Effects of CD38-Chimeric Antigen Receptors by Affinity Optimization. Mol Ther. 2017 Aug 2;25(8):1946-1958. doi: 10.1016/j.ymthe.2017.04.024. Epub 2017 May 13. — View Citation

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Godfrey J, Benson DM Jr. The role of natural killer cells in immunity against multiple myeloma. Leuk Lymphoma. 2012 Sep;53(9):1666-76. doi: 10.3109/10428194.2012.676175. Epub 2012 Apr 19. Review. — View Citation

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Hari PN, McCarthy PL. Multiple myeloma: future directions in autologous transplantation and novel agents. Biol Blood Marrow Transplant. 2013 Jan;19(1 Suppl):S20-5. doi: 10.1016/j.bbmt.2012.11.002. Review. — View Citation

Hideshima T, Podar K, Chauhan D, Ishitsuka K, Mitsiades C, Tai YT, Hamasaki M, Raje N, Hideshima H, Schreiner G, Nguyen AN, Navas T, Munshi NC, Richardson PG, Higgins LS, Anderson KC. p38 MAPK inhibition enhances PS-341 (bortezomib)-induced cytotoxicity against multiple myeloma cells. Oncogene. 2004 Nov 18;23(54):8766-76. — View Citation

Hsi ED, Steinle R, Balasa B, Szmania S, Draksharapu A, Shum BP, Huseni M, Powers D, Nanisetti A, Zhang Y, Rice AG, van Abbema A, Wong M, Liu G, Zhan F, Dillon M, Chen S, Rhodes S, Fuh F, Tsurushita N, Kumar S, Vexler V, Shaughnessy JD Jr, Barlogie B, van Rhee F, Hussein M, Afar DE, Williams MB. CS1, a potential new therapeutic antibody target for the treatment of multiple myeloma. Clin Cancer Res. 2008 May 1;14(9):2775-84. doi: 10.1158/1078-0432.CCR-07-4246. — View Citation

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* Note: There are 30 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0 Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0 6 months
Secondary Overall remission rate defined by the standard response criteria for myeloma for each arm Overall remission rate defined by the standard response criteria for myeloma for each arm 8 weeks
Secondary Duration of CAR-positive T cells in circulation Duration of CAR-positive T cells in circulation 6 months
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