Immuno-PRISM (PRecision Intervention Smoldering Myeloma)

NCT05469893 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 22-154
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to test the anti-cancer activity of Teclistamab and to compare it with Lenalidomide + Dexamethasone combination in people with high risk smoldering multiple myeloma. People with smoldering multiple myeloma (SMM) usually do not have symptoms but are at risk for progressing to active multiple myeloma (MM). Multiple Myeloma is a cancer of the plasma cells, which are an important part of the immune system. Patients with active multiple myeloma generally require treatment but there are currently no approved therapies for smoldering multiple myeloma. The names of the study drugs involved in this study are:

• Teclistamab
• Lenalidomide (also called Revlimid)
• Dexamethasone (also called Decadron)

Conditions

High-risk Smoldering Multiple Myeloma; Smoldering Multiple Myeloma; Multiple Myeloma

Keywords

High-risk smoldering Multiple Myeloma; Smoldering Multiple Myeloma; Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate (CRR)

  The complete response rate (CRR) was defined as the proportion of participants achieving complete response (CR) based on International Myeloma Working Group (IMWG) Response criteria. CR defined as requires all of the following: * Disappearance of the original monoclonal protein from the blood and urine on at least two determinations for a minimum of six weeks by immunofixation studies. * \<5% plasma cells in the bone marrow on at least two determinations for a minimum of six weeks. * No increase in the size or number of lytic bone lesions (development of a compression fracture does not exclude response). * Disappearance of soft tissue plasmacytomas for at least six weeks.

  Cycle 2 Day 1 through end of follow up (each cycle is 28 days).

Secondary Outcomes (11)

• Minimal Residual Disease (MRD) Negativity

  Baseline, Cycle 6 Day 1, Cycle 13 Day 1, end of treatment, 1, 2, & 3 year after end of treatment (each cycle is 28 day).

• Progression-free survival (PFS) until progression to myeloma

  Every 6 months, up to 3 years after treatment discontinuation.

• Progression-free survival (PFS-2) post initiation of overt myeloma therapy

  Every 6 months, up to 3 years after treatment discontinuation.

• Time to progression

  Cycle 2 Day1 through end of follow up, an average of 5 years (each cycle is 28 days).

• Duration of Response (DOR)

  Cycle 2 Day1 through end of follow up, an average of 5 years (each cycle is 28 days).

Study Arms (2)

Lenalidomide + Dexamethasone (LD)

ACTIVE COMPARATOR

Each study treatment cycle lasts 28 days. Participants will be randomized into either Teclistamab arm or Lenalidomine + Dexamethoasone arm * Lenalidomine * Dexamethoasone

Drug: Lenalidomide; Drug: Dexamethasone

Teclistamab

EXPERIMENTAL

Each study treatment cycle lasts 28 days. Participants will be randomized into either Teclistamab arm or Lenalidomine + Dexamethoasone arm \- Teclistamab-Per Protocol

Drug: Teclistamab

Interventions

Teclistamab DRUG

Intravenous (IV) dosage and timing per protocol design

Also known as: JNJ-64007957

Teclistamab

Lenalidomide DRUG

Oral, dosage and timing per protocol design

Also known as: Revlimid

Lenalidomide + Dexamethasone (LD)

Dexamethasone DRUG

Oral, dosage and timing per protocol design

Lenalidomide + Dexamethasone (LD)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years.
• \) High risk SMM defined as having 1 of the following 2 criteria: High risk per "20-2-20" Criteria defined as presence of any two of the following:
• \-- Serum M spike ≥ 2 gm/dL, Involved to uninvolved free light chain (FLC) ratio≥ 20, Bone marrow Plasma Cell (BMPC) % ≥ 20%
• OR total score of 9 using the following scoring system:
• FLC Ratio \>10-25 = 2, \>25-40 = 3, \> 40 = 5
• Serum M-Protein (g/dL) \>1.5-3 = 3, \>3 = 4
• BMPC% \>15-20 = 2, \>20-30 = 3, \>30-40 = 5, \>40 = 6
• Fluorescence In Situ Hybridization (FISH) abnormality (t(4,14), t(14,16), 1q gain, or del13q = 2
• \) Presence of ≥10% BMPC and at least one of the following:
• \-- Evolving pattern:
• evolving Monoclonal Protein (eMP) (≥10% increase in Monoclonal Protein/Immunoglobulin (Ig)) within the first 6 months (only if M-protein ≥3 g/dl) and/or ≥25% increase in M/Ig within the first 12 months, with a minimum required increase of 0.5 g/dl in M-protein and/or 500 mg/dl in Ig.
• Evolving change in hemoglobin (eHb) ≥0.5 g/dl decrease within 12 months of diagnosis;
• Progressive involved light chain increase on two successive evaluation
• Abnormal Plasma Cell immunophenotype (≥ 95% of BMPCs are clonal) and reduction of ≥1 uninvolved immunoglobulin isotype. (Only IgG; IgA and IgM will be considered)
• High risk cytogenetics defined as presence of t(4;14), t(14;16), t(14;20), 17p deletion, TP53 mutation, 1q21 gain

You may not qualify if:

• Prior SMM directed therapy administered within 6 months of beginning treatment on study. To avoid including primary refractory cases to the lenalidomide arm, participants who received a prior lenalidomide-based therapy should have had at least an Minimal Response (MR) to be considered on this trial.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Diagnosed or treated for another malignancy within 2 years of enrollment
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Plans to father a child while enrolled in this study or within 90 days after receiving the last dose of study drug.
• Pregnant or breast-feeding or planning to become pregnant while enrolled in this study or within 90 days after receiving the last dose of study drug.
• Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) or SARS-CoV-2 (COVID- 19).
• Participants who are seropositive because of hepatitis B virus vaccine are eligible.
• Participants who are positive for SARS-COV-2 antibody, HIV1 and 2 antibody, hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded.
• Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients (refer to the teclistamab Investigator's Brochure and appropriate package inserts).
• Prior or concurrent exposure to any of the following:
• Investigational vaccine within 4 weeks
• Live, attenuated vaccine within 4 weeks before randomization.
• Monoclonal antibody therapy within 21 days
• Cytotoxic therapy within 14 days

Sponsors & Collaborators

• Irene Ghobrial, MD: lead
• Janssen Research & Development, LLC: collaborator

Study Sites (3)

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

Oregon Health & Science University

Portland, Oregon, 97239, United States

RECRUITING

MeSH Terms

Conditions

Smoldering Multiple Myeloma; Multiple Myeloma

Interventions

Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Hypergammaglobulinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Paraproteinemias; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Irene C Ghobrial, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Irene Ghobrial, MD

CONTACT

617-632-4198; Irene_ghobrial@dfci.harvard.edu

Ashlee Sturtevant, MSc

CONTACT

617-632-4101; Ashlee_Sturtevant@DFCI.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: June 7, 2022
• First Posted: July 22, 2022
• Study Start: August 10, 2022
• Primary Completion (Estimated): July 31, 2030
• Study Completion (Estimated): July 31, 2030
• Last Updated: April 24, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (3)