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A Study of Ve-VRD or S-VRD Combined With CART-ASCT-CART2 Treatment in Patients With Primary Plasma Cell Leukemia

Primary Purpose

Plasma Cell Leukemia

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
anti-BCMA CAR-T
Sponsored by
Institute of Hematology & Blood Diseases Hospital, China
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Plasma Cell Leukemia

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. Age ≥ 18 years and ≤ 65 years. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2. Life expectancy at least 3 months Definitive diagnosis of pPCL: meet the diagnosis criteria of multiple myeloma (refer to the Chinese guidelines for the diagnosis and management of multiple myeloma (revised 2022) criteria) and meeting any of the following: the proportion of tumor plasma cells in peripheral blood leukocytes ≥ 5%; absolute value of peripheral blood tumorigenic plasma cells exceeds 2×10^9/L. Patients have not received previous anti-myeloma related therapy. Measurable disease, as defined by at lease one of the following: Serum monoclonal paraprotein (M-protein) level ≥5g/L. urine M-protein level ≥200 mg/24 hours. If the serum and urine M-protein are unmeasurable, abnormal serum free light chain (FLC) ratio and affected FLC ≥10 mg/dL. Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological examination. 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) : ANC ≥ 1.0 x 10^9/L, PLT ≥ 50 x 10^9/L. 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: Total bilirubin<1.5 x upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST); Creatinine clearance ≥ 50mL/min (calculated using Cockroft-Gault formula). Patients must be able to take prophylactic anticoagulant therapy as recommended by the study. 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. Willing and able to complete the study procedures and follow-up examinations. Exclusion Criteria: Secondary plasma cell leukemia. With central nervous system (CNS) involvement. Ineligible for autologous stem cell transplantation, such as severe cardiopulmonary disorders. Known intolerant, allergic, or resistant to glucocorticoids, bortezomib, lenalidomide, Venetoclax, Selinexor and BCMA-CART cellular products. Patients 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. Patients with unstable or active cardiovascular system disease, meeting any of the following: Unstable angina pectoris, symptomatic myocardial ischaemia, myocardial infarction or coronary artery reconstruction within 180 days prior to the first dose. Uncontrolled hypertension (>140/90 mmHg with blood pressure fluctuations of more than 180/100 mmHg over a 6-month period). Uncontrolled and clinically significant conduction abnormalities (e.g. patients with ventricular arrhythmias controlled by antiarrhythmic medication), not excluding patients with 1st degree atrioventricular (AV) block or asymptomatic left anterior bundle branch block/right bundle branch block (LAFB/RBBB)). Congestive heart failure (CHF) classification ≥ grade 3 as defined by the New York Heart Association (NYHA). Left ventricular ejection fraction (LVEF) <50% on echocardiography. History of stroke or intracranial haemorrhage within 12 months prior to screening. Presence of a serious thrombotic event prior to treatment. Known positive serology for HIV or HIV seropositivity. Active hepatitis B or C infection. Screening requires serologic testing for hepatitis. If hepatitis B surface antigen and hepatitis B core antibody were positive, a negative DNA polymerase chain reaction (PCR) result was needed before enrollment (after anti-hepatitis B therapy, a negative DNA polymerase PCR result was confirmed before enrollment). If the hepatitis C antibody was positive, the RNA PCR test should be negative prior to enrollment. Ongoing active infection. Prior history of malignancies, unless free of the disease for ≥ 5 years. Pregnant or breast feeding females. 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. 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. Necessary medication or supportive therapy is contraindicated with study treatment. Any other medical condition or comorbidity that might interfere with subject's participation. Patients undergoing other experimental therapies. Patients are not willing to or cannot comply with study scheme.

Sites / Locations

  • Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical SciencesRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ve-VRD or S-VRD Combined CART-ASCT-CART2

Arm Description

Ve-VRD or S-VRD:Venetoclax or Selinexor Plus Bortezomib, Lenalidomide and Dexamethasone Venetoclax 400mg po QD; Selinexor 60mg po QW Bortezomib SC 1.3mg/sqm on day 1,8,15,22, Lenalidomide oral 25 mg on day 1-21, and Dexamethasone 40mg on day 1,8,15,22 in a 28-day cycle. Autologous BCMA-directed CAR-T cells, Double infusion intravenously at a target dose of 2 x 10^6 anti-BCMA CAR+T cells/kg respectively. Participants will receive X-VRD induction, first CAR-T infusion, XVR consolidation, ASCT followed by the second CAR-T infusion, and XR maintenance. X: Venetoclax or Selinexor. Patients with t(11;14) at diagnosis will Venetoclax and patients without t(11;14) at diagnosis will Selinexor.

Outcomes

Primary Outcome Measures

Safety and Tolerability
The incidence of treatment-emergent adverse events (TEAEs)
Overall response rate (ORR)
ORR(including sCR / CR / VGPR / PR, based on IMWG criteria)
Progression free survival (PFS)
Is defined as time from first induction date to first documentation of PD, or death due to any cause, whichever occurs first.

Secondary Outcome Measures

Complete response rate (CRR)
CR or better is defined as percentage of participants who achieve a CR response or Stringent Complete Response (sCR) response according to IMWG criteria
Overall survival (OS)
Is defined as time from first induction date to time of death due to any cause
MRD-negative Rate
MRD negative by flow cytometry
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)

Full Information

First Posted
April 29, 2023
Last Updated
May 13, 2023
Sponsor
Institute of Hematology & Blood Diseases Hospital, China
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1. Study Identification

Unique Protocol Identification Number
NCT05870917
Brief Title
A Study of Ve-VRD or S-VRD Combined With CART-ASCT-CART2 Treatment in Patients With Primary Plasma Cell Leukemia
Official Title
A Prospective, Single-center, Phase II Study of Venetoclax/Selinexor Plus VRD Combined With CART-ASCT-CART2 Treatment in Patients With Newly Diagosed Primary Plasma Cell Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 25, 2023 (Actual)
Primary Completion Date
April 2025 (Anticipated)
Study Completion Date
April 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Institute of Hematology & Blood Diseases Hospital, China

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes

5. Study Description

Brief Summary
This is a single-arm, open-label study to evaluate the efficacy and safety of Ve-VRD or S-VRD (Venetoclax or Selinexor, plus Bortezomib, Lenalidomide and Dexamethasone) regimen combined with CART-ASCT-CART2 in Chinese patients with newly diagnosed primary plasma cell leukemia.
Detailed Description
The study is a prospective, single-arm, single-centre, phase II study designed to evaluate the efficacy and safety of treatment with the Ve-VRD or S-VRD (Venetoclax or Selinexor, plus Bortezomib, Lenalidomide and Dexamethasone) regimen in combination with CART-ASCT-CART2 in Chinese patients with newly diagnosed primary plasma cell leukemia. Patients with t(11;14) at diagnosis receive 3 cycles of induction therapy with Ve-VRD regimen and patients without t(11;14) with S-VRD regimen followed by the first infusion of CAR-T cells. Patients then received 3 cycles of Ve-VR or S-VR consolidation therapy, followed by ASCT and the second infusion of CAR-T cells. And VeR or SR maintenance starts on day 100 after ASCT.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Plasma Cell Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ve-VRD or S-VRD Combined CART-ASCT-CART2
Arm Type
Experimental
Arm Description
Ve-VRD or S-VRD:Venetoclax or Selinexor Plus Bortezomib, Lenalidomide and Dexamethasone Venetoclax 400mg po QD; Selinexor 60mg po QW Bortezomib SC 1.3mg/sqm on day 1,8,15,22, Lenalidomide oral 25 mg on day 1-21, and Dexamethasone 40mg on day 1,8,15,22 in a 28-day cycle. Autologous BCMA-directed CAR-T cells, Double infusion intravenously at a target dose of 2 x 10^6 anti-BCMA CAR+T cells/kg respectively. Participants will receive X-VRD induction, first CAR-T infusion, XVR consolidation, ASCT followed by the second CAR-T infusion, and XR maintenance. X: Venetoclax or Selinexor. Patients with t(11;14) at diagnosis will Venetoclax and patients without t(11;14) at diagnosis will Selinexor.
Intervention Type
Biological
Intervention Name(s)
anti-BCMA CAR-T
Other Intervention Name(s)
Venetoclax or Selinexor Plus Bortezomib, Lenalidomide and Dexamethasone
Intervention Description
Autologous BCMA-directed CAR-T cells, the double infusion intravenously at a target dose of 2.0 x 10^6 anti-BCMA CAR+T cells/kg respectively
Primary Outcome Measure Information:
Title
Safety and Tolerability
Description
The incidence of treatment-emergent adverse events (TEAEs)
Time Frame
2 year
Title
Overall response rate (ORR)
Description
ORR(including sCR / CR / VGPR / PR, based on IMWG criteria)
Time Frame
after induction therapy, 1 month after the first CAR-T cell transfusion, the consolidation therapy ends, 6 months after the second CAR-T cell transfusion
Title
Progression free survival (PFS)
Description
Is defined as time from first induction date to first documentation of PD, or death due to any cause, whichever occurs first.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Complete response rate (CRR)
Description
CR or better is defined as percentage of participants who achieve a CR response or Stringent Complete Response (sCR) response according to IMWG criteria
Time Frame
after induction therapy, 1 month after the first CAR-T cell transfusion, the consolidation therapy ends, 6 months after the second CAR-T cell transfusion
Title
Overall survival (OS)
Description
Is defined as time from first induction date to time of death due to any cause
Time Frame
1 year
Title
MRD-negative Rate
Description
MRD negative by flow cytometry
Time Frame
after induction therapy, 1 month after the first CAR-T cell transfusion, the consolidation therapy ends, 6 months after the second CAR-T cell transfusion
Title
Duration of Remission (DOR)
Description
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)
Time Frame
2 year
Other Pre-specified Outcome Measures:
Title
The CART cell duration in vivo
Description
The copies of BCMA-CART DNA in peripheral blood with qPCR method
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. Age ≥ 18 years and ≤ 65 years. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2. Life expectancy at least 3 months Definitive diagnosis of pPCL: meet the diagnosis criteria of multiple myeloma (refer to the Chinese guidelines for the diagnosis and management of multiple myeloma (revised 2022) criteria) and meeting any of the following: the proportion of tumor plasma cells in peripheral blood leukocytes ≥ 5%; absolute value of peripheral blood tumorigenic plasma cells exceeds 2×10^9/L. Patients have not received previous anti-myeloma related therapy. Measurable disease, as defined by at lease one of the following: Serum monoclonal paraprotein (M-protein) level ≥5g/L. urine M-protein level ≥200 mg/24 hours. If the serum and urine M-protein are unmeasurable, abnormal serum free light chain (FLC) ratio and affected FLC ≥10 mg/dL. Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological examination. 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) : ANC ≥ 1.0 x 10^9/L, PLT ≥ 50 x 10^9/L. 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: Total bilirubin<1.5 x upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST); Creatinine clearance ≥ 50mL/min (calculated using Cockroft-Gault formula). Patients must be able to take prophylactic anticoagulant therapy as recommended by the study. 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. Willing and able to complete the study procedures and follow-up examinations. Exclusion Criteria: Secondary plasma cell leukemia. With central nervous system (CNS) involvement. Ineligible for autologous stem cell transplantation, such as severe cardiopulmonary disorders. Known intolerant, allergic, or resistant to glucocorticoids, bortezomib, lenalidomide, Venetoclax, Selinexor and BCMA-CART cellular products. Patients 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. Patients with unstable or active cardiovascular system disease, meeting any of the following: Unstable angina pectoris, symptomatic myocardial ischaemia, myocardial infarction or coronary artery reconstruction within 180 days prior to the first dose. Uncontrolled hypertension (>140/90 mmHg with blood pressure fluctuations of more than 180/100 mmHg over a 6-month period). Uncontrolled and clinically significant conduction abnormalities (e.g. patients with ventricular arrhythmias controlled by antiarrhythmic medication), not excluding patients with 1st degree atrioventricular (AV) block or asymptomatic left anterior bundle branch block/right bundle branch block (LAFB/RBBB)). Congestive heart failure (CHF) classification ≥ grade 3 as defined by the New York Heart Association (NYHA). Left ventricular ejection fraction (LVEF) <50% on echocardiography. History of stroke or intracranial haemorrhage within 12 months prior to screening. Presence of a serious thrombotic event prior to treatment. Known positive serology for HIV or HIV seropositivity. Active hepatitis B or C infection. Screening requires serologic testing for hepatitis. If hepatitis B surface antigen and hepatitis B core antibody were positive, a negative DNA polymerase chain reaction (PCR) result was needed before enrollment (after anti-hepatitis B therapy, a negative DNA polymerase PCR result was confirmed before enrollment). If the hepatitis C antibody was positive, the RNA PCR test should be negative prior to enrollment. Ongoing active infection. Prior history of malignancies, unless free of the disease for ≥ 5 years. Pregnant or breast feeding females. 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. 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. Necessary medication or supportive therapy is contraindicated with study treatment. Any other medical condition or comorbidity that might interfere with subject's participation. Patients undergoing other experimental therapies. Patients are not willing to or cannot comply with study scheme.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gang An, PhD&MD
Phone
86-022-23909171
Email
angang@ihcams.ac.cn
Facility Information:
Facility Name
Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
City
Tianjin
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gang An, PhD&MD
Phone
008613502181109
Email
angang@ihcams.ac.cn

12. IPD Sharing Statement

Learn more about this trial

A Study of Ve-VRD or S-VRD Combined With CART-ASCT-CART2 Treatment in Patients With Primary Plasma Cell Leukemia

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