Elimination of Minimal Residual Disease After Transplant

NCT05690984 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PRO00046592
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, single-arm, phase II study that will enroll multiple myeloma (MM) patients with persistent bone marrow minimal residual disease (MRD) post autologous stem cell transplant (ASCT) irrespective of the International Myeloma Working Group (IMWG) response.

Conditions

Multiple Myeloma

Keywords

minimal residual disease; multiple myeloma; next-generation sequencing

Outcome Measures

Primary Outcomes (1)

• The number of subjects who have less than MRD.

  Bone marrow MRD negative at a cutoff sensitivity of ≤1x10\^5 sequence copies as measured by the clonoSEQ® next-generation sequencing assay at the end of IsaRd treatment.

  One year

Study Arms (1)

Isatuximab in combination with lenalidomide and dexamethasone.

EXPERIMENTAL

The isatuximab, lenalidomide, and dexamethasone (IsaRD) therapy will be administered on an outpatient basis.

Drug: Dexamethasone; Drug: Isatuximab; Drug: Lenalidomide

Interventions

Dexamethasone DRUG

Dexamethasone will be used for the double purpose of premedication and therapeutic effect. On Day 1 of Cycle 1, subjects will be administered 40 mg dexamethasone as an IV infusion. On Days 8, 15, 22 of Cycle 1 and Days 1 and 15 of Cycles 2-4, dexamethasone will be given as a single oral dose of 40 mg. For Cycles 5-12, dexamethasone will be given as a single oral dose of 4 mg on Days 1 and 15.

Also known as: Decadron, Dexasone, Diodex, Hexadrol, Maxidex

Isatuximab in combination with lenalidomide and dexamethasone.

Isatuximab DRUG

Following premedication (if applicable), subjects will be given isatuximab 10 mg/kg body weight as an intravenous (IV) infusion on Days 1, 8, 15, and 22 (i.e., weekly) during Cycle 1 and on Days 1 and 15 (i.e., Q2W) during Cycles 2-12.

Also known as: Sarclisa

Isatuximab in combination with lenalidomide and dexamethasone.

Lenalidomide DRUG

On Days 1-21 for all 12 cycles, lenalidomide will be given to subjects as a single daily oral dose.

Also known as: Revlimid

Isatuximab in combination with lenalidomide and dexamethasone.

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.
• Eastern Cooperative Oncology Group (ECOG) Performance Status criteria of 0-2.
• Must have archival bone marrow sample at time of diagnosis that can be used for clonality identification for NGS if not already performed.
• Presence of residual bone marrow minimal residual disease (MRD) positivity by clonoSEQ® next-generation sequencing (NGS) 90-120 days post autologous stem cell transplantation.
• Histologically confirmed diagnosis of symptomatic multiple myeloma (patients with multiple myeloma with secondary amyloidosis are eligible, but no amyloid treatment will be allowed while on study).
• Received autologous stem cell transplant as upfront therapy for myeloma (defined as ASCT within one year of diagnosis of symptomatic MM).
• Adequate organ function as defined below:
• Absolute neutrophil count (ANC) ≥1,000/mm\^3.
• Platelet count ≥75,000/mm\^3; platelet transfusions to help patients meet eligibility criteria are not allowed within seven days before study enrollment.
• Total bilirubin ≤1.5 x the upper limit of the normal range (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x ULN
• Pregnancy It is not known what effects this treatment has on human pregnancy or development of the embryo or fetus. Therefore, female subjects participating in this study should avoid becoming pregnant, and male subjects should avoid impregnating a female partner. Non-sterilized female subjects of reproductive age and male subjects should use effective methods of contraception through defined periods during and after study treatment as specified below.
• Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a female of childbearing potential (FCBP), OR
• A FCBP who must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to and again within 24 hours prior to starting study medication and before each cycle of study treatment and must either commit to continue abstinence from heterosexual intercourse or apply a highly effective method of birth control during the intervention period and for at least five months after the last dose of isatuximab treatment Male participants: A male participant, even if surgically sterilized (i.e., status post-vasectomy), must agree to use contraception during the intervention period and for at least five months after the last dose of isatuximab treatment and refrain from donating sperm during this period.

You may not qualify if:

• Evidence of MM disease progression any time prior to enrollment.
• Administration or planned administration of any other concomitant chemotherapy, immunotherapy, or any ancillary therapy that would be considered a treatment of multiple myeloma from Day +30 post-transplant through discontinuation from study. Local radiation therapy is allowed. Subjects may be on corticosteroids if they are being given for disorders other than multiple myeloma (e.g., adrenal insufficiency, rheumatoid arthritis, etc.)
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• Prior organ transplant requiring immunosuppressive therapy.
• Known to be human immunodeficiency virus (HIV) positive.
• Known to have hepatitis A, B, or C active infection. If hepatitis positive, patient may still be per the notes below.
• Uncontrolled or active hepatitis B virus (HBV) infection: Patient with positive HBsAg and/or HBV DNA.
• Of Note:
• Patient can be eligible if anti-HBc IgG positive (with or without positive anti-HBs) but HBsAg and HBV DNA are negative.
• If anti-HBV therapy in relation with prior infection was started before initiation of investigational medicinal product, the anti-HBV therapy and monitoring should continue throughout the study treatment period.
• Patient with negative HBsAg and positive HBV DNA observed during screening period will be evaluated by a specialist for start of anti-viral treatment: study treatment could be proposed if HBV DNA becomes negative and all the other study criteria are still met.
• Active hepatitis C virus (HCV) infection: positive HCV RNA and negative anti-HCV.
• Of Note:
• Patients with antiviral therapy for HCV started before initiation of investigational medicinal product and positive HCV antibodies are eligible. The antiviral therapy for HCV should continue throughout the treatment period until seroconversion.
• Patients with positive anti-HCV and undetectable HCV RNA without antiviral therapy for HCV are eligible.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasm, Residual

Interventions

Dexamethasone; Calcium Dobesilate; isatuximab; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Sabarinath Radhakrishnan, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 10, 2023
• First Posted: January 19, 2023
• Study Start: June 26, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)