Protocol summary

Study aim
Determining Safety and Maximum Tolerated Dose of Anti-BCMA CAR-NK Therapy in Relapsed or Refractory Multiple Myeloma
Design
The trial is a single-arm interventional phase 1-2 research (Not randomized and not blinded) on 10 patients aimed to examine the safety and define the maximum tolerated dosage (MTD) of cord blood-derived CAR-NK cells in patients with relapsed and refractory multiple myeloma.
Settings and conduct
This study is a single-group clinical trial to evaluate the safety and maximum tolerated dose of allogeneic in-vitro manipulated Natural Killer Cells for relapsed refractory multiple myeloma at the Hematology-Oncology-Stem Cell Transplantation Research Center (HORCSCT) of Tehran University and BMT center of Taleghani Hospital.
Participants/Inclusion and exclusion criteria
Inclusion criteria: Relapsed or refractory multiple myeloma with detectable BCMA Signed written informed consent. Exclusion criteria: Pregnant/lactating women; infections; use of immunosuppressors;
Intervention groups
Routin treatment + infusion of BCMA CAR NK cells The preparation regimen includes cyclophosphamide and fludarabine. The CAR-NK cells are injected with a single dose of CAR-NK cells including either (10 million) or (50 million) or (100 million) cells per kilogram of the patient's body weight. Increasing the dose continues until reaching the maximum determined dose (100 million) or the occurrence of dose-limiting toxicity.
Main outcome variables
Incidence of dose-limiting toxicity; Assessment of Maximum Tolerated Dose; Overall Remission Rate; Progression-free survival; Duration of Response

General information

Reason for update
Acronym
IRCT registration information
IRCT registration number: IRCT20200413047063N4
Registration date: 2024-03-17, 1402/12/27
Registration timing: registered_while_recruiting

Last update: 2024-03-17, 1402/12/27
Update count: 0
Registration date
2024-03-17, 1402/12/27
Registrant information
Name
Masoud Soleimani
Name of organization / entity
Tarbiat Modares University
Country
Iran (Islamic Republic of)
Phone
+98 21 8288 4508
Email address
soleimani.masoud@gmail.com
Recruitment status
recruiting
Funding source
Expected recruitment start date
2024-01-20, 1402/10/30
Expected recruitment end date
2026-01-20, 1404/10/30
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Determining Safety and Maximum Tolerated Dose (MTD) of Anti-BCMA CAR-NK Therapy in Relapsed or Refractory Multiple Myeloma
Public title
Immune cell therapy in Relapsed or Refractory Multiple Myeloma
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
1. Age 18-80 years with expected survival > 3 months. 2. Confirmed diagnosis of active multiple myeloma with detectable BCMA expression in malignant cells. 3. Relapsed or refractory disease with at least 2 prior lines of treatment, including a proteasome inhibitor and immunomodulator, without achieving significant efficacy. 4. Measurable disease at screening according to IMWG criteria, as defined by any of the following: Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level being as defined; or light chain MM without measurable disease in the serum or the urine; serum immunoglobulin free light chain disease dL and abnormal serum immunoglobulin kappa/lambda free light chain ratio. 5. ECOG performance status of 0-1. 6. Acceptable cardiac, liver, and kidney function. 7. Signed written informed consent.
Exclusion criteria:
1. Pregnant or lactating women. 2. Uncontrolled active infection, HIV infection, or positive syphilis serology reaction. 3. Active hepatitis B or hepatitis C infection. 4. Recent or current use of glucocorticoids or other immunosuppresses. 5. Severe cardiac, liver, renal insufficiency, diabetes, or other diseases. 6. Participation in other clinical research in the past three months.
Age
From 18 years old to 80 years old
Gender
Both
Phase
1-2
Groups that have been masked
No information
Sample size
Target sample size: 10
Randomization (investigator's opinion)
N/A
Randomization description
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Single
Other design features

Secondary Ids

1

Registry name
NA
Secondary trial Id
NA
Registration date
2024-02-29, 1402/12/10

Ethics committees

1

Ethics committee
Name of ethics committee
Ethics committee of Tehran University of medical sciences,
Street address
Tehran University of medical science, Felestin St., Keshavarz Blvd., Tehrans,
City
Tehran
Province
Tehran
Postal code
IR.TUMS.MEDICINE.REC
Approval date
2023-12-31, 1402/10/10
Ethics committee reference number
IR.TUMS.MEDICINE.REC.1402.442

Health conditions studied

1

Description of health condition studied
Multiple myeloma in relapse
ICD-10 code
C90.02
ICD-10 code description
Multiple myeloma in relapse

Primary outcomes

1

Description
Incidence of dose-limiting toxicity (DLTs)
Timepoint
Daily during the first seven days after the injection and then weekly until 4 weeks
Method of measurement
History, Physical exam, and lab test

2

Description
Overall Remission Rate (ORR)
Timepoint
8 weeks after CAR-NK cells infusion
Method of measurement
Assessed using International Myeloma Working Group (IMWG) criteria

Secondary outcomes

1

Description
Progression-free survival (PFS)
Timepoint
48 weeks after CAR-NK cells infusion
Method of measurement
Assessed using IMWG criteria.

2

Description
Duration of Response (DOR)
Timepoint
48 weeks after CAR-NK cells infusion
Method of measurement
Assessed using IMWG criteria.

Intervention groups

1

Description
Intervention group: A single infusion of BCMA CAR NK cells, The patient is brought to the isolation room 4 days before receiving CAR-NK cells and gets a chemotherapeutic conditioning treatment (days - 4 to - 1). The preparation regimen includes cyclophosphamide at a dose of 30 mg/kg/day from day -3 to day -2 (for two days) and fludarabine at a dose of 30 mg/m2/day from day -4 to day -2 (for three days).On day zero, the CAR-NK cells, which have been prepared in the laboratory clean room, are injected with a single dose of CAR-NK cells including either (10 million) or (50 million) or (100 million) cells per kilogram of the patient's body weight. Increasing the dose continues until reaching the maximum determined dose (100 million) or the occurrence of dose-limiting toxicity.To evaluate the maximum tolerated cell dose, the 3+3 formula is used. The minimum initial safe dose includes ten million cells per kilogram of the patient's body weight, which is injected into the first three patients, and if no dose-limiting toxicity occurs, for the next three patients, the dose is increased by half a log (fifty million cells to per kilogram of the patient's body weight). The cell dose will be increased up to a maximum dose of 100 million cells per kilogram of body weight unless dose-limiting toxicity occurs. The definition of the maximum tolerated cell dose according to the ICMJE guidelines includes the highest cell dose, which is shown by a maximum of 2 out of 6 patients.Based on this, dose-limiting toxicity (DLT) is defined as follows:1- Acute and severe allergic reaction (grade 3 and 4) following the injection of CAR-NK cells2- Cytopenia lasting more than 28 days from the time of injection3- Acute GVHD of grade 2 to 44- Unexpected acute and severe toxicity (grades 3 and 4) Infusion of CAR-NK cells is performed in the inpatient department of the hospital and in the isolation room qualified for cell therapy. During this period, patients are under strict monitoring in terms of treatment side effects and toxicity related to the infusion of CAR-NK cells, and routine laboratory tests are performed daily (and more if needed).For the injection of these cells, the standard methods determined for lymphocyte injection (DLI), including the administration of appropriate premedication, the availability of the necessary drugs for anaphylaxis, and the careful monitoring of the patient within 4 hours after the injection.If any complication occurs during the infusion, the injection will be stopped and the necessary measures will be taken based on the CTCAE table and classification below.In grade 1, only the infusion is stopped.Grade 2-3; Stopping the infusion and treatment including corticosteroids and antihistaminesGrade 4: In addition to the above, it is recommended to carry out resuscitation and care measures in the ICU departmentStatistical Analysis: The collected data will be analyzed using appropriate statistical methods, including survival analysis, logistic regression, and correlation analyses, to determine the safety and efficacy outcomes and identify potential prognostic factors.Ethical Considerations: This study will be conducted in full compliance with ethical guidelines and regulations, ensuring patient confidentiality.
Category
Treatment - Other

Recruitment centers

1

Recruitment center
Name of recruitment center
Shariati hospital
Full name of responsible person
Mohammad Vaezi
Street address
Tehran, North Kargar, Shariati Hospital
City
Tehran
Province
Tehran
Postal code
14117 13135
Phone
+98 21 8802 9600
Email
m-vaezi@sina.tums.ac.ir
Web page address

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Mohammad Vaezi
Street address
Felestin St., Keshavarz Blvd., Tehran
City
Tehran
Province
Tehran
Postal code
1416634793
Phone
+98 912 287 5993
Email
m-vaezi@sina.tums.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Tehran University of Medical Sciences
Proportion provided by this source
20
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic

2

Sponsor
Name of organization / entity
Payesh company
Full name of responsible person
Masoud Soleimani
Street address
No. 105, West Baqerkhan street, Tehran
City
Tehran
Province
Tehran
Postal code
1313814117
Phone
+98 912 287 5993
Email
soleimani.masoud@gmail.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Payesh company
Proportion provided by this source
80
Public or private sector
Private
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Persons

Person responsible for general inquiries

Contact
Name of organization / entity
Shahid Beheshti University of Medical Sciences
Full name of responsible person
Masoud Soleimani
Position
Professor
Latest degree
Ph.D.
Other areas of specialty/work
Hematology
Street address
Jalal-e-Al-e-Ahmad Hwy, North Kargar Street, Tehran Province
City
Tehran
Province
Tehran
Postal code
14117 13135
Phone
+98 912 287 5993
Email
soleimani.masoud@gmail.com

Person responsible for scientific inquiries

Contact
Name of organization / entity
Shahid Beheshti University of Medical Sciences
Full name of responsible person
Masoud Soleimani
Position
Professor
Latest degree
Ph.D.
Other areas of specialty/work
Hematology
Street address
Jalal-e-Al-e-Ahmad Hwy, North Kargar Street, Tehran Province
City
Tehran
Province
Tehran
Postal code
14117 13135
Phone
+98 912 287 5993
Email
soleimani.masoud@gmail.com

Person responsible for updating data

Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Mohammad Vaezi
Position
Associate professor
Latest degree
Specialist
Other areas of specialty/work
Hematology
Street address
Jalal-e-Al-e-Ahmad Hwy, North Kargar Street, Tehran Province .
City
Tehran
Province
Tehran
Postal code
14117 13135
Phone
+98 912 287 5993
Email
m-vaezi@sina.tums.ac.ir

Sharing plan

Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to make this available
Study Protocol
Undecided - It is not yet known if there will be a plan to make this available
Statistical Analysis Plan
Undecided - It is not yet known if there will be a plan to make this available
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Undecided - It is not yet known if there will be a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Undecided - It is not yet known if there will be a plan to make this available
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