Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT02958397
Other study ID # TMMU-BTC-011
Secondary ID
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date October 2016
Est. completion date October 2020

Study information

Verified date June 2019
Source Southwest Hospital, China
Contact Cheng Qian, MD, PhD
Phone 0086-023-68765461
Email cqian3184@163.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The overall purpose of this study is to explore the therapeutic effect of CD33-targeted chimeric antigen receptor T(CAR-T) cells in the treatment of Myeloid Malignancies.


Description:

Great progress has been made in the treatment of relapsed and refractory B cell malignancies with CD19-targeted CAR-T cells. However, for myeloid malignancies, which has higher morbidity, trials of CAR-T is few. CD33 is expressed on most myeloid leukemia cells so it is a ideal target for CAR-T. This trial is designed and conducted to test the safety and effectiveness of CD33-targeted CAR-T.


Recruitment information / eligibility

Status Recruiting
Enrollment 45
Est. completion date October 2020
Est. primary completion date October 2019
Accepts healthy volunteers No
Gender All
Age group 14 Years to 75 Years
Eligibility Inclusion Criteria:

1. CD33-expressing myeloid 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. CD33 expression of the malignant cells must be detected by immunohistochemistry or by flow cytometry.

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 we think not eligible for participation in the research.

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
Anti-CD33-CAR-transduced T cells
The first 3 enrolled patients will receive autologous-derived CD33-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.

Locations

Country Name City State
China Southwest Hospital of Third Millitary Medical University Chongqing Chongqing

Sponsors (1)

Lead Sponsor Collaborator
Southwest Hospital, China

Country where clinical trial is conducted

China, 

Outcome

Type Measure Description Time frame Safety issue
Primary Adverse Events That Are Related to Treatment Determine the toxicity profile of the CD33 targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0. 3 years
Secondary In vivo existence of Anti-CD33 CAR-T cells 3 years
Secondary Reaction Rate of Treatment 3 years
See also
  Status Clinical Trial Phase
Not yet recruiting NCT06383572 - Phase I/II Study of Engineered T Cell Receptor-Modified NK Cells Targeting PRAME in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapse/Refractory Myeloid Malignancies Phase 1/Phase 2
Completed NCT01731951 - Imetelstat Sodium in Treating Participants With Primary or Secondary Myelofibrosis Phase 2
Recruiting NCT02958384 - A Clinical Research of LeY-Targeted CAR-T in Myeloid Malignancies Phase 1/Phase 2
Recruiting NCT05775406 - Safety and Clinical Activity of KT-253 in Adult Patients With High Grade Myeloid Malignancies, Acute Lymphocytic Leukemia, Lymphoma, Solid Tumors Phase 1
Recruiting NCT05807659 - Fractionated Busulfan Conditioning Regimen for Allo-HSCT in Non-remission Myeloid Malignancies Phase 2
Active, not recruiting NCT02452697 - Ph2 NK Cell Enriched DCIs w/wo RLR9 Agonist, DUK-CPG-001 From Donors Following Allogeneic SCT Phase 2
Completed NCT04778410 - Study of Magrolimab Combinations in Participants With Myeloid Malignancies Phase 2
Terminated NCT01366612 - PRO#1278: Fludarabine and Busulfan vs. Fludarabine, Busulfan and Total Body Irradiation Phase 3
Completed NCT03270748 - Post Transplant High-Dose Cy as GvHD Prophylaxis in 1 HLA Mismatched Unrelated HSCT for Myeloid Malignancies Phase 2
Recruiting NCT05115630 - Off-the-shelf NK Cells + SCT for Myeloid Malignancies Phase 1/Phase 2
Recruiting NCT05796570 - A Pilot Study to Evaluate the Feasibility of Post-Hematopoietic Stem Cell Transplant Prophylaxis With Decitabine Combined With Filgrastim for Children and Young Adults With AML, MDS and Related Myeloid Malignancies Phase 2