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Clinical Trial Using Humanized CART Directed Against BCMA (ARI0002h) in Patients With Relapsed/Refractory Multiple Myeloma to Proteasome Inhibitors, Immunomodulators and Anti-CD38 Antibody.

Primary Purpose

Relapsed/Refractory Multiple Myeloma

Status

Active

Phase

Phase 1

Locations

Spain

Study Type

Interventional

Intervention

Adult differentiated autologous T-cells with anti-BCMA specificity

About this trial

This is an interventional treatment trial for Relapsed/Refractory Multiple Myeloma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients between the age of 18 and 75 years with diagnosis of multiple myeloma
Disease measurable by monoclonal component in serum and/or urine or by free light chains in serum according to the eligibility criteria for clinical trials of the International Myeloma Working Group
Previous two or more lines of treatment. Patients must have received at least a proteasome inhibitor (such as bortezomib or carfilzomib), an immunomodulatory drug (lenalidomide or pomalidomide) and an anti-CD38 monoclonal antibody (such as daratumumab)
Refractory to the last line of treatment
ECOG functional status ranging from 0 to 2
Life expectancy over 3 months
Patients who, after being informed, give their consent by signing the Informed Consent document.

Exclusion Criteria:

Previous allogeneic transplant in the prior 6 months to inclusion or GVHD that requires active systemic immunosuppressive treatment
Absolute lymphocyte count <0.1x10^9/ L
Previous neoplasia, except if patients have been in complete remission > 3 years, except for cutaneous carcinoma (non-melanoma)
Active infection that requires treatment
Active infection by HIV, HBV or HCV.
Uncontrolled medical disease
Severe organic condition that meets any of the following criteria: EF <40%, DLCO <40%, EGFR <50 ml / min, bilirubin> 3 times normal value (except Gilbert syndrome)
Previous diagnosis of symptomatic AL amyloidosis
Pregnant or lactating women. Women of childbearing age should have a negative pregnancy test in the screening phase
Women of childbearing age, including those whose last menstrual cycle was in the year prior to screening, who cannot or do not wish to use highly effective contraceptive methods from the beginning until the end of the study.
Men who cannot or do not wish to use highly effective contraceptive methods from the beginning to the end of the study.
Contraindication to receive conditioning chemotherapy

Sites / Locations

Hospital U. de Santiago de Compostela
Clinica Universidad de Navarra
Hospital Clinic of Barcelona
Hospital 12 de Octubre
Hospital Clínico Universitario Virgen de La Arrixaca
Hospital Universitario de Salamanca
Hospital Universitario Virgen Del Rocío

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ARI0002h

Arm Description

Adult differentiated autologous T-cells from peripheral blood, expanded and transducted with a lentivirus to express a chimeric antigen receptor with anti-BCMA (TNFRSF17) specificity conjugated to the 4-1BB co-stimulatory region and signal-transduction CD3z that has been humanized

Outcomes

Primary Outcome Measures

Overall response rate (ORR)

Cytokine release syndrome rate

Secondary Outcome Measures

Duration of the response

Response rate

Complete response rate (CR)

Overall response rate (ORR)

Time to complete response

Response rate of extramedullary disease by PET-CT

Negative MRD rate in bone marrow

Response rate of extramedullary disease by PET-TC

Progression free survival (PFS)

Overall survival (OS) defined as the time elapsed between the infusion of ARI0002h and the death of the patient from any cause

Presence of tumor lysis syndrome

Presence of cytokine release syndrome

Presence of neurological toxicity

Presence of prolonged cytopenia

Persistence of CART BCMA ARI0002 in peripheral blood

Expression of BCMA

Levels of soluble BCMA in serum

Full Information

NCT ID

NCT04309981

First Posted

March 9, 2020

Last Updated

August 25, 2023

Sponsor

Sara V. Latorre

Collaborators

Fondos ARI (Assistencia Recerca Intensiva), Instituto de Salud Carlos III, Fondo Social La Caixa

1. Study Identification

Unique Protocol Identification Number

NCT04309981

Brief Title

Clinical Trial Using Humanized CART Directed Against BCMA (ARI0002h) in Patients With Relapsed/Refractory Multiple Myeloma to Proteasome Inhibitors, Immunomodulators and Anti-CD38 Antibody.

Official Title

Pilot Study of the Infusion of Differentiated Autologous T-cells From Peripheral Blood, Expanded and Transduced With a Lentivirus to Express a Chimeric Antigen Receptor With Anti-BCMA (TNFRSF17) Specificity Humanized Conjugated With the Co-stimulatory Region 4-1BB and Signal-transduction CD3z (ARI0002h) in Patients With Relapsed/Refractory Multiple Myeloma With Previous Treatment With Proteasome Inhibitor, Immunomodulatory Drug and Anti-CD38 Monoclonal Antibody

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

May 27, 2020 (Actual)

Primary Completion Date

April 1, 2025 (Anticipated)

Study Completion Date

April 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Sara V. Latorre

Collaborators

Fondos ARI (Assistencia Recerca Intensiva), Instituto de Salud Carlos III, Fondo Social La Caixa

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

To assess the safety and efficacy of CARTBCMA ARI0002h in patients with relapsed/refractory multiple myeloma who have received treatment with proteasome inhibitor, immunomodulatory drug and anti-CD38 monoclonal antibody.

6. Conditions and Keywords

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

Relapsed/Refractory Multiple Myeloma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

73 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ARI0002h

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Adult differentiated autologous T-cells with anti-BCMA specificity

Other Intervention Name(s)

CARTBCMA

Intervention Description

After pretreatment, adult differentiated autologous T-cells with a chimeric antigen receptor with anti-BCMA specificity will be transfused.

Primary Outcome Measure Information:

Title

Overall response rate (ORR)

Time Frame

3 months

Title

Cytokine release syndrome rate

Time Frame

within 30 days of first infusion

Secondary Outcome Measure Information:

Title

Duration of the response

Time Frame

up to 36 months after treatment

Title

Response rate

Time Frame

over the first year

Title

Complete response rate (CR)

Time Frame

at month 3 and month 6 of first infusion

Title

Overall response rate (ORR)

Time Frame

at month 6 of first infusion

Title

Time to complete response

Time Frame

up to 36 months after treatment

Title

Response rate of extramedullary disease by PET-CT

Time Frame

up to 36 months after treatment

Title

Negative MRD rate in bone marrow

Time Frame

at month 3 and month 6 of first infusion

Title

Response rate of extramedullary disease by PET-TC

Time Frame

at month 3

Title

Progression free survival (PFS)

Time Frame

at month 12, and up to 36 months after treatment

Title

Overall survival (OS) defined as the time elapsed between the infusion of ARI0002h and the death of the patient from any cause

Time Frame

up to 36 months after treatment

Title

Presence of tumor lysis syndrome

Time Frame

up to 36 months after treatment

Title

Presence of cytokine release syndrome

Time Frame

up to 36 months after treatment

Title

Presence of neurological toxicity

Time Frame

up to 36 months after treatment

Title

Presence of prolonged cytopenia

Time Frame

up to 36 months after treatment

Title

Persistence of CART BCMA ARI0002 in peripheral blood

Time Frame

month 1, 2, 3, 4, 5, 6 and every 6 months until 2 years of follow up

Title

Expression of BCMA

Time Frame

at screening, at day +28, at day +100, at month 6, 12, 18 and 24

Title

Levels of soluble BCMA in serum

Time Frame

at screening, at day 0, +3, +7,+14,+28, +70 +100, at month 4, 5, 6, 7, 8, 9, 1,11, 12, 18 and 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients between the age of 18 and 75 years with diagnosis of multiple myeloma Disease measurable by monoclonal component in serum and/or urine or by free light chains in serum according to the eligibility criteria for clinical trials of the International Myeloma Working Group Previous two or more lines of treatment. Patients must have received at least a proteasome inhibitor (such as bortezomib or carfilzomib), an immunomodulatory drug (lenalidomide or pomalidomide) and an anti-CD38 monoclonal antibody (such as daratumumab) Refractory to the last line of treatment ECOG functional status ranging from 0 to 2 Life expectancy over 3 months Patients who, after being informed, give their consent by signing the Informed Consent document. Exclusion Criteria: Previous allogeneic transplant in the prior 6 months to inclusion or GVHD that requires active systemic immunosuppressive treatment Absolute lymphocyte count <0.1x10^9/ L Previous neoplasia, except if patients have been in complete remission > 3 years, except for cutaneous carcinoma (non-melanoma) Active infection that requires treatment Active infection by HIV, HBV or HCV. Uncontrolled medical disease Severe organic condition that meets any of the following criteria: EF <40%, DLCO <40%, EGFR <50 ml / min, bilirubin> 3 times normal value (except Gilbert syndrome) Previous diagnosis of symptomatic AL amyloidosis Pregnant or lactating women. Women of childbearing age should have a negative pregnancy test in the screening phase Women of childbearing age, including those whose last menstrual cycle was in the year prior to screening, who cannot or do not wish to use highly effective contraceptive methods from the beginning until the end of the study. Men who cannot or do not wish to use highly effective contraceptive methods from the beginning to the end of the study. Contraindication to receive conditioning chemotherapy

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Carlos Fernandez de Larrea, MD,PhD

Organizational Affiliation

Hospital Clinic of Barcelona

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hospital U. de Santiago de Compostela

City

Santiago De Compostela

State/Province

A Coruña

ZIP/Postal Code

15706

Country

Spain

Facility Name

Clinica Universidad de Navarra

City

Pamplona

State/Province

Navarra

ZIP/Postal Code

31008

Country

Spain

Facility Name

Hospital Clinic of Barcelona

City

Barcelona

ZIP/Postal Code

08036

Country

Spain

Facility Name

Hospital 12 de Octubre

City

Madrid

ZIP/Postal Code

28041

Country

Spain

Facility Name

Hospital Clínico Universitario Virgen de La Arrixaca

City

Murcia

ZIP/Postal Code

30120

Country

Spain

Facility Name

Hospital Universitario de Salamanca

City

Salamanca

ZIP/Postal Code

37007

Country

Spain

Facility Name

Hospital Universitario Virgen Del Rocío

City

Sevilla

ZIP/Postal Code

41013

Country

Spain

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34876408

Citation

Oliver-Caldes A, Jimenez R, Espanol-Rego M, Cibeira MT, Ortiz-Maldonado V, Quintana LF, Castillo P, Guijarro F, Tovar N, Montoro M, Benitez-Ribas D, Bataller A, Gonzalez-Navarro EA, Cid J, Lozano M, Perez-Amill L, Martin-Antonio B, Mena MP, Moreno DF, Rodriguez-Lobato LG, Campistol JM, Calvo G, Blade J, Rosinol L, Juan M, Pascal M, Urbano-Ispizua A, Fernandez de Larrea C. First report of CART treatment in AL amyloidosis and relapsed/refractory multiple myeloma. J Immunother Cancer. 2021 Dec;9(12):e003783. doi: 10.1136/jitc-2021-003783. Erratum In: J Immunother Cancer. 2022 Nov;10(11):

Results Reference

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Clinical Trial Using Humanized CART Directed Against BCMA (ARI0002h) in Patients With Relapsed/Refractory Multiple Myeloma to Proteasome Inhibitors, Immunomodulators and Anti-CD38 Antibody.

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