A Clinical Research of CD30-Targeted CAR-T in Lymphocyte Malignancies

• ClinicalTrials.gov Identifier: NCT02958410
• Recruitment Status: Recruiting
• First Posted: November 8, 2016
• Last Update Posted: June 25, 2019
• Sponsor: Southwest Hospital, China
• Information provided by (Responsible Party): Shiqi Li, Southwest Hospital, China

Study Description

Brief Summary:

The overall purpose of this study is to explore the therapeutic effect of BCMA-targeted chimeric antigen receptor T(CAR-T) cells in the treatment of lymphocyte derived malignancies.

Condition or disease	Intervention/treatment	Phase
Leukemia; Lymphoma	Biological: Anti-CD30-CAR-transduced T cells	Phase 1; Phase 2

Detailed Description:

CD30 is originally described as a marker of Hodgkin's and Reed-Sternberg cells in Hodgkin's lymphoma. CD30 antibody has been applied to treat lymphocyte derived malignancies. To explore the potency of CD30 in CAR-T therapy, this trial is designed and conducted to test the safety and effect of CD30-targeted CAR-T.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 45 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Clinical Research of CD30-Targeted CAR-T in Lymphocyte Malignancies
• Study Start Date: October 2016
• Estimated Primary Completion Date: October 2019
• Estimated Study Completion Date: October 2020

Arms and Interventions

Arm

Intervention/treatment

Experimental: Lymphocyte Malignancies; The trial will be conducted in a manner of simon two-stage design with Anti-CD30-CAR-transduced T cells, beginning in the first stage with the aim of over 30% reaction rate among 15 patients with B cell malignancies. Only when the expected reaction rate is achieved the 30 patients left can be recruited.

Biological: Anti-CD30-CAR-transduced T cells; The first 3 enrolled patients will receive autologous-derived CD30-targeted CAR-T cells on day 1, 2 and 3 with respective 10%, 30% and 60% of the total expected dosage after receiving lymphodepleting chemotherapy. If the 3 patients don't display severe toxicity, the next patients enrolled will get infused in 2 days with respective 40% and 60% total dosage.; Other Name: CD30-targeted CAR-T cells

Outcome Measures

Primary Outcome Measures :

1. Adverse Events That Are Related to Treatment [ Time Frame: 3 years ]
   Determine the toxicity profile of the BCMA targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.

Secondary Outcome Measures :

1. In vivo existence of Anti-CD30 CAR-T cells [ Time Frame: 3 years ]
2. Reaction Rate of Treatment [ Time Frame: 3 years ]

Eligibility Criteria

• Ages Eligible for Study: 14 Years to 75 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. CD30-expressing lymphocyte malignancy must be assured and must be relapsed or refractory disease. According to current traditional therapies, there must be no available alternative curative therapies and subjects must be either ineligible for allogeneic stem cell transplant (SCT), have refused SCT, or have disease activity that prohibits SCT at this time.
2. Patients enrolled must have an evaluated score above 60 with KPS.
3. CD30 expression of the malignant cells must be detected by immunohistochemistry or by flow cytometry. In general immunohistochemistry will be used for lymph node biopsies, flow cytometry will be used for peripheral blood and bone marrow samples.
4. Gender is not limited, age from 14 years to 75 years.
5. Patients must have measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis.
6. Patients are expected to survive for more than 3 months by their physicians at the time of enrollment.
7. Adequate absolute CD3 count estimated need to be assured for obtaining target cell dose based on dosage cohorts.

8. Subjects with the following CNS status are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy:

   CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of WBCs; CNS 2, defined as presence of < 5/uL WBCs in CSF and cytospin positive for blasts, or > 5/uL WBCs but negative by Steinherz/Bleyer algorithm CNS3 with marrow disease who has failed salvage systemic and intensive IT chemotherapy (and therefore not eligible for radiation)

9. Ability to give informed consent.
10. Cardiac function: Left ventricular ejection fraction greater than or equal to 40% by MUGA or cardiac MRI, or fractional shortening greater than or equal to 28% by ECHO or left ventricular ejection fraction greater than or equal to 50% by ECHO.
11. Renal function: Creatinine level of peripheral blood is required no greater than 133umol/L.
12. Females of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus.
13. Patients with history of allogeneic stem cell transplantation are eligible if there is no evidence of active GVHD and no longer taking immunosuppressive agents for at least 30 days prior to enrollment.
14. Patients volunteer to participate in the research.

Exclusion Criteria:

1. Evident signs suggesting that patients are potentially allergic to cytokines.
2. Frequent infection history and recent infection is uncontrolled.
3. Patients with concomitant genetic syndrome: patients with Down syndrome, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome
4. Active acute or chronic graft-versus-host disease (GVHD) or requirement of immunosuppressant medications for GVHD within 4 weeks of enrollment.
5. Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. For additional details regarding use of steroid and immunosuppressant medications.
6. Pregnancy and nursing females.
7. HIV infection.
8. Active hepatitis B or active hepatitis C.
9. Participation in a prior investigational study within 4 weeks prior to enrollment or longer if required by local regulation. Participation in non-therapeutic research studies is allowed.
10. Class III/IV cardiovascular disability according to the New York Heart Association Classification.
11. Patients with a known history or prior diagnosis of other serious immunologic, malignant or inflammatory disease.
12. Other situations researchers think not eligible for participation in the research.

Contacts and Locations

Contacts

Contact: Cheng Qian, MD, PhD; 0086-023-68765461; cqian3184@163.com

Contact: Shiqi Li, MD; 0086-13206140093; Lystch@qq.com

Locations

China, Chongqing

Southwest Hospital of Third Millitary Medical University; Recruiting

Chongqing, Chongqing, China, 400000

Contact: Cheng Qian, PhD 008615086883400 cqian3184@163.com

Contact: Zhi Yang, PhD 008613206140093 Lystch@qq.com

Principal Investigator: Cheng Qian, PhD

Sponsors and Collaborators

Southwest Hospital, China

Investigators

• Principal Investigator: Cheng Qian, MD, PhD; Biotherapy Center of Southwest Hospital

More Information

• Responsible Party: Shiqi Li, Principal Investigator of Biotherapy Center, Southwest Hospital, China
• ClinicalTrials.gov Identifier: NCT02958410
• Other Study ID Numbers: TMMU-BTC-010
• First Posted: November 8, 2016
• Last Update Posted: June 25, 2019
• Last Verified: June 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Shiqi Li, Southwest Hospital, China:

CD30; CAR-T

Additional relevant MeSH terms:

Neoplasms