Phase I Study of CD19-CAR-T2 Cells for Patients With Chemotherapy Resistant or Refractory CD19+ Acute Leukemia

Acute Leukemia Clinical Trial

Official title:

CD19-CAR-T2 Cells for Relapse/Refractory CD19 Positive Acute Leukemia—a Phase I Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02822326
• Other study ID #: No.GDREC2016198H
• Status: Recruiting
• Phase: Phase 1
• First received: June 28, 2016
• Last updated: September 8, 2017
• Start date: January 2016
• Est. completion date: September 2019

Study information

• Verified date: September 2017
• Source: Guangdong General Hospital
• Contact: Xin Du, Dr.
• Phone: +86 20 83827812
• Email: miyadu[@]hotmial.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and efficacy of chimeric antigen receptor 19 (CD19-CAR-T2 Cells) infusions in patients with chemotherapy resistant or refractory CD19+ acute Leukemia.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: September 2019
• Est. primary completion date: September 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 65 Years

Eligibility

Inclusion Criteria:

• Patient with relapsed and/or refractory CD19 positive B-cell acute leukemia

• Eastern Cooperative Oncology Group (ECOG) performance status « 3

• ALT/ AST « 3x normal

• Bilirubin < 2.0 mg/dl

• Creatinine < 2.5 mg/dl and less than 2.5x normal for age

• LVEF» 45%

• Accept white blood cell collection

• Provide informed consent

Exclusion Criteria:

• Previous treatment with investigational gene or cell therapy medicine products

• Solitary extramedullary relapse

• Active hepatitis B , hepatitis C or HIV infection

• Uncontrolled active infection

• Presence of grade 2-4 acute or extensive chronic GVHD

• Active CNS involvement: epilepsy, paresis, aphasia, stroke, severe head trauma,

• Dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness, etc.

• Any uncontrolled active medical disorder that would preclude participation as outlined.

• Received non-diagnostic purposes major surgery within the past 4 weeks

• Participated in any other clinical study within the past 4 weeks

• Used murine biological products (except blinatumomab), unless it is proved no anti-mouse antibodies exist.

• Pregnancy or breast-feeding women

• Use of prohibited drugs:

• Steroids: Therapeutic doses of steroids must be stopped > 72 hours prior to CD19-CAR-T2 Cells infusion

• Allogeneic cellular therapy: Any donor lymphocyte infusions (DLI) must be completed > 4 weeks prior to CD19-CAR-T2 Cells infusion

• GVHD therapies: Any drug used for GVHD must be stopped > 4 weeks prior to CD19-CAR-T2 Cells infusion

• Chemotherapy: i. The following drugs must be stopped > 1 week prior to CTL019 infusion and should not be administered concomitantly or following lymphodepleting chemotherapy: hydroxyurea, vincristine, 6-mercaptopurine, 6-thioguanine, methotrexate <25 mg/m2, cytosine arabinoside < 10 mg/m2/day, asparaginase; ii. The following drugs must be stopped > 4 weeks prior to CTL019 infusion: salvage chemotherapy (e.g. clofarabine, cytosine arabinoside > 100 mg/m2, anthracyclines, cyclophosphamide), excluding the required lymphodepleting chemotherapy drugs

• Any situation that may increase the risk of the test or interfere with the test results

Related Conditions & MeSH terms

• Acute Disease
• Acute Leukemia
• Leukemia

Intervention

Biological:
• CD19-CAR-T2 Cells

Locations

Country	Name	City	State
China	Guangdong General Hospital	Guangzhou	Guangdong

Sponsors (3)

Lead Sponsor	Collaborator
Guangdong General Hospital	Chinese Academy of Sciences, Guangdong Zhaotai InVivo Biomedicine Company Limited

Country where clinical trial is conducted

China, 

References & Publications (12)

Chimeric Antigen Receptor-Modified T Cells in Chronic Lymphoid Leukemia; Chimeric Antigen Receptor-Modified T Cells for Acute Lymphoid Leukemia; Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia. N Engl J Med. 2016 Mar 10;374(10):998. doi: 10.1056/NEJMx160005. — View Citation

Forman SJ, Rowe JM. The myth of the second remission of acute leukemia in the adult. Blood. 2013 Feb 14;121(7):1077-82. doi: 10.1182/blood-2012-08-234492. Epub 2012 Dec 14. Review. — View Citation

Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ, Reaman GH, Carroll WL. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children's oncology group. J Clin Oncol. 2012 May 10;30(14):1663-9. doi: 10.1200/JCO.2011.37.8018. Epub 2012 Mar 12. — View Citation

Jensen MC, Popplewell L, Cooper LJ, DiGiusto D, Kalos M, Ostberg JR, Forman SJ. Antitransgene rejection responses contribute to attenuated persistence of adoptively transferred CD20/CD19-specific chimeric antigen receptor redirected T cells in humans. Biol Blood Marrow Transplant. 2010 Sep;16(9):1245-56. doi: 10.1016/j.bbmt.2010.03.014. Epub 2010 Mar 19. — View Citation

Kochenderfer JN, Dudley ME, Kassim SH, Somerville RP, Carpenter RO, Stetler-Stevenson M, Yang JC, Phan GQ, Hughes MS, Sherry RM, Raffeld M, Feldman S, Lu L, Li YF, Ngo LT, Goy A, Feldman T, Spaner DE, Wang ML, Chen CC, Kranick SM, Nath A, Nathan DA, Morton KE, Toomey MA, Rosenberg SA. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol. 2015 Feb 20;33(6):540-9. doi: 10.1200/JCO.2014.56.2025. Epub 2014 Aug 25. — View Citation

Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, Fry TJ, Orentas R, Sabatino M, Shah NN, Steinberg SM, Stroncek D, Tschernia N, Yuan C, Zhang H, Zhang L, Rosenberg SA, Wayne AS, Mackall CL. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015 Feb 7;385(9967):517-528. doi: 10.1016/S0140-6736(14)61403-3. Epub 2014 Oct 13. — View Citation

Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF, Mahnke YD, Melenhorst JJ, Rheingold SR, Shen A, Teachey DT, Levine BL, June CH, Porter DL, Grupp SA. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014 Oct 16;371(16):1507-17. doi: 10.1056/NEJMoa1407222. — View Citation

Porter DL, Hwang WT, Frey NV, Lacey SF, Shaw PA, Loren AW, Bagg A, Marcucci KT, Shen A, Gonzalez V, Ambrose D, Grupp SA, Chew A, Zheng Z, Milone MC, Levine BL, Melenhorst JJ, June CH. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med. 2015 Sep 2;7(303):303ra139. doi: 10.1126/scitranslmed.aac5415. — View Citation

Pulte D, Redaniel MT, Jansen L, Brenner H, Jeffreys M. Recent trends in survival of adult patients with acute leukemia: overall improvements, but persistent and partly increasing disparity in survival of patients from minority groups. Haematologica. 2013 Feb;98(2):222-9. doi: 10.3324/haematol.2012.063602. Epub 2012 Aug 28. — View Citation

Raetz EA, Bhatla T. Where do we stand in the treatment of relapsed acute lymphoblastic leukemia? Hematology Am Soc Hematol Educ Program. 2012;2012:129-36. doi: 10.1182/asheducation-2012.1.129. Review. — View Citation

Savoldo B, Ramos CA, Liu E, Mims MP, Keating MJ, Carrum G, Kamble RT, Bollard CM, Gee AP, Mei Z, Liu H, Grilley B, Rooney CM, Heslop HE, Brenner MK, Dotti G. CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. J Clin Invest. 2011 May;121(5):1822-6. doi: 10.1172/JCI46110. Epub 2011 Apr 11. — View Citation

Schrappe M, Hunger SP, Pui CH, Saha V, Gaynon PS, Baruchel A, Conter V, Otten J, Ohara A, Versluys AB, Escherich G, Heyman M, Silverman LB, Horibe K, Mann G, Camitta BM, Harbott J, Riehm H, Richards S, Devidas M, Zimmermann M. Outcomes after induction failure in childhood acute lymphoblastic leukemia. N Engl J Med. 2012 Apr 12;366(15):1371-81. doi: 10.1056/NEJMoa1110169. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The maximum tolerated dose(MTD) of CD19 positive relapsed/ refractory acute leukimia treated wtih CD19-CAR-T2 cells		24 weeks
Secondary	Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment	Adverse events and laboratory abnormalities (type, frequency and severity)	12 months
Secondary	Overall Response Rate	Overall Response Rate (ORR), which includes Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi), as determined by assessments of peripheral blood, bone marrow, CNS symptoms, physical exam (PE) and CSF. The primary endpoint will be based on the IRC assessment. The local investigator's assessed results will be used for sensitivity analysis.	12 months