A Study of Bortezomib, Lenalidomide and Dexamethasone (VRd) Followed by BCMA CAR-T Therapy in Transplant-Ineligible Patients With Primary Plasma Cell Leukemia

Plasma Cell Leukemia Clinical Trial

Official title:

Safety and Efficiency of VRd Combining BCMA CAR-T Regimen for Transplant-ineligible Patients With Primary Plasma Cell Leukemia: a Prospective, Single-arm, Single-center, Phase II Study.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05979363
• Other study ID #: CAREMM-002
• Status: Recruiting
• Phase: Phase 2
• Start date: July 1, 2023
• Est. completion date: July 1, 2028

Study information

• Verified date: August 2023
• Source: Institute of Hematology & Blood Diseases Hospital
• Contact: Gang An, PhD&MD
• Phone: 86-022-23909171
• Email: angang[@]ihcams.ac.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single-arm, open-label study to evaluate the efficacy and safety of VRD-based regimen combined with BCMA CAR-T in transplant-ineligible patients with primary plasma cell leukemia

Description:

The study is a prospective, single-arm, single-centre, phase II study designed to evaluate the efficacy and safety of treatment with VRD-based regimen combined with BCMA CAR-T in transplant-ineligible patients with primary plasma cell leukemia. Patients received 3 courses of induction therapy with VRD-based regimen followed by infusion of BCMA CAR-T cells. Patients then received 3 courses of VR consolidation therapy, followed by VR maintenance therapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: July 1, 2028
• Est. primary completion date: July 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age = 18 years and = 75 years.

2. Participants with documented primary plasma cell leukemia according to IMWG diagnostic criteria (circulating plasma cells =5%, determined by morphology on peripheral blood smear; or absolute value of peripheral blood tumorigenic plasma cells exceeds 2×10^9/L).

3. Measurable disease, at screening as defined by any of the following: Serum monoclonal paraprotein (M-protein) level =1.0 g/dL or urine M-protein level =200 mg/24 hours; or Light chain MM without measurable disease in serum or urine: serum Ig free-light chain (FLC) =10 mg/dL and abnormal serum Ig kappa lambda FLC ratio.

4. Not considered for high-dose chemotherapy with Autologous Stem Cell Transplant (ASCT) due to: Ineligible due to advanced age (=65); or Ineligible evaluated by researchers; or Eastern Cooperative Oncology Group Performance Status grade of 3 or 4; or Repeated hematopoietic stem cell mobilization failure; or Deferral of high-dose chemotherapy with ASCT as initial treatment.

5. Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological examination.

6. All screening blood biochemistry: tests should be performed according to the protocol and within 14 days before enrollment. Screening laboratory values must meet the following criteria: a.TBIL<2 x upper limit of normal (ULN) (<3 x ULN in patients with Gilbert's syndrome); b.AST and ALT <3 x ULN.; c. Creatinine clearance = 30mL/min (calculated using Cockroft-Gault formula).

7. Routine blood tests (performed within 7 days, no RBC transfusion, no G-CSF/GM-CSF/platelet agonists, no drug correction within 14 days before screening, no PLT transfusion within 7 days) : WBC = 1.5 x 109/L, ANC = 1.0 x 109/L, Hb = 70 g/L PLT = 75 x 109/L (if BMPC < 50%) or PLT = 50 x 109/L (if BMPC = 50%).

8. Patients must be able to take prophylactic anticoagulant therapy as recommended by the study.

9. The woman is not breastfeeding, is not pregnant and agrees not to be pregnant during the study period and for the following 12 months. Male patients agreed that their spouse would not become pregnant during the study period and for 12 months thereafter.

Exclusion Criteria:

1. Documented active amyloidosis.

2. Documented with central nervous system (CNS) invasion.

3. Prior exposure to any BCMA-targeted therapy or CAR-T therapy.

4. Patients with peripheral neuropathy greater than grade 2 or peripheral neuropathy greater than grade 2 with pain at baseline, regardless of whether they were currently receiving medical therapy.

5. Known intolerance, hypersensitivity, or contraindication to glucocorticoids, bortezomib, lenalidomide, and BCMA-CART cellular products.

6. Seropositive for human immunodeficiency virus (HIV)

7. Hepatitis B infection

8. Hepatitis C infection

9. Life expectancy of <6 months

10. Women who are pregnant or breastfeeding

11. Any active gastrointestinal dysfunction that affects the patient's ability to swallow tablets, or any active gastrointestinal dysfunction that may affect the absorption of the studied treatment medication

12. Subjects had major surgery within 2 weeks before randomization (for example, general anesthesia), or is not fully recovered from the surgery, or surgery is arranged during study period.

13. Received live attenuated vaccine within 4 weeks prior to study treatment.

14. According to the researcher's judgment, any condition including but not limited to serious mental illness, medical illness, or other symptoms/conditions that may affect study treatment, compliance, or the capability of providing informed consent.

15. Necessary medication or supportive therapy is contraindicated with study treatment.

16. Any diseases or complications that may interfere with the study.

17. Patients are not willing to or cannot comply with study scheme.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Plasma Cell
• Plasma Cell Leukemia

Intervention

Biological:
• anti-BCMA CAR-T
Autologous BCMA-directed CAR-T cells, infusion intravenously at a target dose of 2.0-4.0 x 10^6 anti-BCMA CAR+T cells/kg.

Drug:
• VRD-based regimen
Bortezomib, Lenalidomide and Dexamethasone

Locations

Country	Name	City	State
China	Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Hematology & Blood Diseases Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The duration of CART cell in vivo	The copies of BCMA-CART DNA in peripheral blood with qPCR method	Up to 1 year
Other	Change from Baseline in Physical status assessed by International Myeloma Working Group Comprehensive Geriatric Assessment (IMWG-CGA) scores	The IMWG-CGA was calculated by combining age, activities of daily living (ADL), instrumental ADL (IADL), and Charlson Comorbidity Index (CCI), which ranges from 0 to 5 with higher scores indicating worse physical condition and greater weakness.	Baseline up to 5 years
Other	Change from Baseline in Physical status assessed by activities of daily living (ADL) scores	The ADL includes 4 items (transfer, bed mobility, toileting, and eating), which range from 0 to 6 scores. A higher score represents worse physical condition and greater weakness.	Baseline up to 5 years
Other	Change from Baseline in Physical status assessed by instrumental activities of daily living (IADL) scores	The IADL includes 5 items (cooking, cleaning, transportation, laundry, and managing finances), which range from 0 to 8 scores. A higher score represents worse physical condition and greater weakness.	Baseline up to 5 years
Other	Change from Baseline in Physical status assessed by Charlson Comorbidity Index (CCI)	The CCI estimates the number and the severity of comorbidities, including nineteen diseases with a score varying from 1 to 6 for each of them in accordance to their severity. The score can range from 0 to 37. A higher score represents more severe comorbidities.	Baseline up to 5 years
Primary	Safety and Tolerability	The incidence of treatment-emergent adverse events (TEAEs)	Up to 2 year
Primary	MRD-negative rate	achieving MRD-negative, as determined by NGS/NGF after consolidation treatment	within 1 week after consolidation treatment
Secondary	Complete response rate (CRR)	CR or better is defined as percentage of participants who achieve a CR response or Stringent Complete Response (sCR) response accoording to the IMWG criteria	within 1 week after induction therapy, 1 month after the CAR-T cell transfusion, within 1 week after consolidation therapy
Secondary	Progression free survival (PFS)	Progression free survival is defined as the time from the date of diagnosis to the date of first documented PD, as defined in the IMWG criteria, or death due to any cause, whichever occurs first	Up to 2 year
Secondary	Overall Survival (OS)	Overall survival is measured from the date of diagnosis to the date of the participant's death.	Up to 5 year
Secondary	Duration of Remission(DOR)	Duration from the first evaluation of at least partial remission (PR) to the onset of disease progression or death due to disease progression (whichever occurs first)	Up to 2 year