Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Smoldering Multiple Myeloma

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Precancerous Conditions

Hypergammaglobulinemia

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immunomodulating Agents

Mechlorethamine

Nitrogen Mustard Compounds

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antimetabolites

Participants will be enrolled into each of the 2 safety run-in phases in a standard 3 + 3 design.

- Participants will undergo study procedures as outlined:

* Apheresis for collection of peripheral blood mononuclear cells (PBMC) will occur on-site
* Stem cell collection on-site post-apheresis per standard care.
* Administration of Cyclophosphamide and fludarabine in pre-determined doses 1 x daily for 3 consecutive days.
* Hospitalization to receive Cilta-cel in per-determined dose per protocol 1 x daily for 3 consecutive days and will remain in the hospital for 2 weeks post cilta-cell infusion.
* Follow-up for 3 years post-treatment and up to 15 years.

Expansion cohort of 14 participants will be enrolled after safety run-in phases, and participants will undergo study procedures as outlined:

* Apheresis for collection of peripheral blood mononuclear cells (PBMC) will occur on-site
* Stem cell collection on-site post-apheresis per standard care.
* Administration of Cyclophosphamide and fludarabine in pre-determined doses 1 x daily for 3 consecutive days.
* Hospitalization to receive Cilta-cel in per-determined dose per protocol 1 x daily for 3 consecutive days and will remain in the hospital for 2 weeks post cilta-cell infusion.
* Follow-up for 3 years post-treatment and up to 15 years.

Genetically modified autologous T-cell immunotherapy, via intravenous infusion per protocol.

Ciltacabtagene Autoleucel

Lymphodepleting conditioning regimen, nitrogen mustard-derivative, via intravenous infusion per standard care.

Lymphodepleting conditioning regimen, synthetic purine nucleoside, via intravenous infusion per standard care.

Fludarabine Phosphate

Irene Ghobrial, MD

Hope Wei

The goal of this research study is to test if ciltacabtagene autoleucel (cilta-cel) is safe and effective in treating participants with high-risk, smoldering myeloma.

The names of the treatment interventions used in this study are:

* Cilta-cel (or chimeric antigen receptor T cells)
* Cyclophosphamide (a lymphodepleting chemotherapy)
* Fludarabine (a lymphodepleting chemotherapy)

This is a Phase II study to test the safety and effectiveness of study therapy cilta-cel in treating participants with high-risk smoldering multiple myeloma (SMM). T cells are a part of a person's immune system which usually helps fight infection and prevents/fights cancer cells.

The U.S. Food and Drug Administration (FDA) has approved cilta-cel as a treatment for relapsed and refractory multiple myeloma but not specifically for smoldering myeloma.

The research study procedures include screening for eligibility, study treatment including evaluations, blood collections, radiologic scans of tumors, bone marrow biopsies, and follow-up visits.

Participation in this study is expected to last about 15 years.

It is expected that about 20 people will take part in this research study.

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational therapy to learn whether the therapy works in treating a specific disease. "Investigational" means that the therapy is being studied.

Janssen Research \& Development, LLC is supporting this research study by providing the study treatment and funding.

CAR- PRISM (PRecision Intervention Smoldering Myeloma)

CAR- PRISM (PRecision Intervention Smoldering Myeloma): A Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA in High-Risk Smoldering Myeloma

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Incidence of Dose Limiting Toxicities (DLTs) during the first 28 days after anti-BCMA CAR-T cell administration.

Dose-Limiting Toxicities (DLTs) will be defined as follows:

* Grade 4 non-hematologic toxicity of any duration including Grade 4 CRS and ICANS
* Grade 3 CRS that does not improve to a grade 2 or less in 72 hours following adequate therapy.
* Grade 3 neurological toxicity of any duration
* Grade 3 toxicity of any duration involving vital organs (cardiac, pulmonary). Exceptions can be made if associated with CRS.
* Other Grade 3 toxicity lasting \> 72 hours. Exceptions may be made for Grade 3 abnormal hepatic or renal function tests that improve to grade 2 or less within 7 days.
* Grade 3 hypersensitivity reaction that is not reversible to Grade 2 or less within 24 hours
* Grade 4 neutropenia or thrombocytopenia lasting more than 28 days

Nature of Dose Limiting Toxicities (DLTs) during the first 28 days after anti-BCMA CAR-T cell administration.

Dose-Limiting Toxicities (DLTs) will be defined as follows:

* Grade 4 non-hematologic toxicity of any duration including Grade 4 CRS and ICANS
* Grade 3 CRS that does not improve to a grade 2 or less in 72 hours following adequate therapy.
* Grade 3 neurological toxicity of any duration
* Grade 3 toxicity of any duration involving vital organs (cardiac, pulmonary). Exceptions can be made if associated with CRS.
* Other Grade 3 toxicity lasting \> 72 hours. Exceptions may be made for Grade 3 abnormal hepatic or renal function tests that improve to grade 2 or less within 7 days.
* Grade 3 hypersensitivity reaction that is not reversible to Grade 2 or less within 24 hours
* Grade 4 neutropenia or thrombocytopenia lasting more than 28 days

Adverse events with onset or worsening on or after date of first dose of study treatment.

AEs with onset or worsening on or after date of first dose of study treatment. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death related to AE. SAE is any untoward medical occurrence that results in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important.

Defined as number of subjects treated with planned target dose divided by total number of subjects treated, and it is done to evaluate the feasibility of the manufacturing process

Defined by the proportion of subjects with the best overall response (BOR). It is the BOR of stringent complete response (sCR), Complete response (CR), VGPR (Very good partial response), and Partial response (PR) at month 3 and month 6 as determined using International Myeloma Working Group (IMWG) Criteria (Kumar et al, 2016).

Proportion of subjects with best overall response (BOR) of stringent complete response (sCR) or complete response (CR) at month 3 as determined by local investigator using International Myeloma Working Group (IMWG) Criteria (Kumar et al, 2016)

Duration of response (DOR) to be assessed, and DOR defined as the time from achievement of stringent complete response (sCR), Complete response (CR), VGPR (Very good partial response), and Partial response (PR) to relapse or death due to multiple myeloma.

Cmax of BCMA analyzed through qPCR-detected transgene of CAR-T concentrations over time in peripheral blood and bone marrow.

Tmax of BCMA analyzed through qPCR-detected transgene of CAR-T concentrations over time in peripheral blood and bone marrow.

AUC of BCMA analyzed through qPCR-detected transgene of CAR-T concentrations over time in peripheral blood and bone marrow.

Clast of BCMA analyzed through qPCR-detected transgene of CAR-T concentrations over time in peripheral blood and bone marrow.

Both cellular and humoral of pre-existing and treatment induced immunogenicity for BCMA CAR-T cellular therapy in smoldering myeloma (SMM).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
CAR- PRISM (PRecision Intervention Smoldering Myeloma)	NCT05767359	Multiple Myelom... Smoldering Mult...	Ciltacabtagene ... Cyclophosphamid... Fludarabine Pho...	18 Years -	Dana-Farber Cancer Institute
CAR- PRISM (PRecision Intervention Smoldering Myeloma)	NCT05767359	Multiple Myelom... Smoldering Mult...	Ciltacabtagene ... Cyclophosphamid... Fludarabine Pho...	18 Years -	Dana-Farber Cancer Institute

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