Post-Autologous Transplant Maintenance With Isatuximab and Lenalidomide in Minimal Residual Disease Positive Multiple Myeloma

Study Purpose

This is a phase II study where patients will undergo isatuximab and lenalidomide maintenance starting at day 90 (+/-30 days) after Autologous Stem Cell Transplant (ASCT) provided they have achieved at least Partial Response (PR).Patients may have received any number of cycles of induction therapy prior to stem cell transplant.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. 12. Patients must be willing to take appropriate DVT prophylaxis, either aspirin, low molecular weight heparin, direct oral anticoagulants, or warfarin while receiving lenalidomide.

Inclusion Criteria:

1. Age > 18 years. 2. Patients must have a confirmed diagnosis of multiple myeloma according to IMWG criteria. Patients with smoldering multiple myeloma, or plasma cell leukemia are not eligible. Patients must not have significant amyloid organ dysfunction per the study chair. 3. R-ISS stage 1, 2 or 3 at diagnosis. If stage at diagnosis is not known, patient may be enrolled if the intent is to treat with single-drug maintenance. 4. Received up to 2 lines of therapy prior to ASCT (as long as they did not meet IMWG refractory disease for CD38 monoclonal antibody or lenalidomide therapies as defined in exclusion). 5. Patients are planned to undergo ASCT with high dose melphalan, or have completed ASCT with high dose melphalan within the last 90 days and have not yet initiated post-ASCT maintenance. 6. Obtain at least partial response according to IMWG criteria after induction therapy and ASCT. 7. ECOG performance status of 0, 1, or 2 within 30 days prior to enrollment. 8. Demonstrate adequate organ function as defined in the table below; all screening labs are to be obtained within 30 days prior enrollment. Hematologic White blood cell (WBC) ≥ 1500/mm3 Absolute Neutrophil Count (ANC) ≥ 1000/mm3 Platelets ≥ 50,000/mm3 Renal Calculated creatinine clearance ≥ 30 mL/min using either the Cockcroft-Gault formula or estimated GFR, and not requiring continuous or intermittent dialysis Hepatic Bilirubin ≤ 2.5 × upper limit of normal (ULN) Aspartate aminotransferase (AST) ≤ 2.5 × ULN Alanine aminotransferase (ALT) ≤ 2.5 × ULN Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT)1 ≤ 2 × ULN Note: Patients on anticoagulation are exempt from meeting this criterion. 9. Standard of care lenalidomide will not be provided by the sponsor or study and therefore study subjects must have confirmed access to lenalidomide for use during the study at the time of enrollment. 10. Must be able to take and swallow oral medication (capsules) whole. Patients may not have any known impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). 11. Females of childbearing potential and males must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 5 months for females, and 1 month for males after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method. Interventions such as IUD, tubal ligation, hormonal (birth control pills, injections, hormonal patches, vaginal rings, or implants), or partner's vasectomy, all count as one method. For women of childbearing potential (WOCBP), a second form must also be used. Men must agree to use a latex condom during sexual activity with a female of childbearing potential, irrespective of a prior vasectomy, during the study treatment and for 1 month after the end of treatment. Females of childbearing potential agree to not plan a pregnancy for 1 month after the last dose of study medication. Females of childbearing potential must agree to ongoing pregnancy testing during the treatment period. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. 12. Patients must be willing to take appropriate DVT prophylaxis, either aspirin, low molecular weight heparin, direct oral anticoagulants, or warfarin while receiving lenalidomide.

Exclusion Criteria:

1. Refractory to anti-CD38 monoclonal antibody therapy OR lenalidomide as defined by the IMWG (defined as non-responsive or progressive disease on therapy or within 60 days of last treatment). 2. MRD negative CR (at a resolution of 10-5) at screening. 3. Prior intolerance to isatuximab or lenalidomide. 4. Prior allogeneic stem cell transplant. 5. Prior solid organ transplant requiring immunosuppressive therapy. 6. Known additional malignancy that is active and/or progressive requiring treatment; exceptions include adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years. 7. Known CNS involvement by multiple myeloma, defined by positive CSF cytology for plasma cells, leptomeningeal involvement, or parenchymal CNS plasmacytoma at time of enrollment. Lumbar puncture is not required. 8. Treatment with any investigational drug within 30 days prior to enrollment. 9. Planned transplant is considered part of tandem autologous transplant approach for newly diagnosed MM. 10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris or coronary angioplasty, unstable cardiac arrhythmia (ongoing cardiac dysrhythmias of NCI Common Terminology Criteria for Adverse Events [CTCAE] v5.0 Grade ≥ 2), intracardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (≥ Grade 3), or known psychiatric illness/social situations that would limit compliance with study requirements. 11. Pregnant women are excluded from this study because lenalidomide is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lenalidomide, breastfeeding should be discontinued if the mother is treated with lenalidomide. 12. Patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) may be enrolled if the viral load by polymerase chain reaction (PCR) is undetectable with active treatment and absolute lymphocyte count ≥ 350/ul. Antiviral therapy for HIV should continue throughout the study. 13. Patients with a positive test for hepatitis B virus surface antigen (HBsAg) and/or HBV DNA indicating uncontrolled or active HBV infection. Patients with negative HBsAg and positive HBV viral load can be evaluated by a specialist for start of anti-viral therapy and study treatment can be proposed if HBV viral load becomes negative and other study criteria are met. Participants can be eligible if anti-HBc IgG is positive, but HBsAg and HBV viral load is negative (i.e., cleared infection). 14. Patients with known hepatitis C virus (HCV) viral load indicating acute or chronic infection might be enrolled if the viral load by PCR is undetectable with/without active treatment. If a patient was started on antiviral therapy prior to study enrollment, antiviral therapy should continue throughout the study. NOTE: HIV, Hep B, and Hep C viral testing is not required and this criterion apply only to patients with a known history of HCV infection.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT05344833
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University of Illinois at Chicago
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Multiple Myeloma
Additional Details

This is a phase II study where patients will undergo isatuximab and lenalidomide maintenance starting at day 90 (+/-30 days) after Autologous Stem Cell Transplant (ASCT) provided they have achieved at least Partial Response (PR).Patients may have received any number of cycles of induction therapy prior to stem cell transplant. Patients will be enrolled prior to ASCT or up to day +90 (+/-30 days) disease reassessment. Patients will undergo disease reassessment per standard of care including Bone Marrow (BM) examination and Minimal Residual Disease (MRD) testing by Next Generation Sequencing (NGS) MRD testing is required at day 90 for patients in Complete Response (CR). In addition, NGS testing must be performed for those patients not in CR who have not previously had initial sample testing for identification of B cell clonality. If patients have failed to achieve CR and have prior baseline testing for B cell clonality, MRD monitoring can be omitted at 90 days as patients will be assumed to be MRD-positive. All patients who fail to achieve MRD-negative CR (at a resolution of 10-5) patients will begin treatment with isatuximab and lenalidomide by day 180 (i.e. all patients in PR, Very Good Partial Response (VGPR) or MRD-positive CR). Patients will be monitored for disease response and have BM testing every 12 months to evaluate for the presence of MRD for a total of 3 years, or until disease progression or unacceptable toxicity. If patients experience progression or relapse at any time, BM testing will be performed.

Arms & Interventions

Arms

Experimental: Isatuximab and Lenalidomide Maintenance

All participants will receive: Isatuximab 10mg/kg IV Days 1,8, 15, 22 Cycle 1 (all cycles 28 days). Isatuximab 10mg/kg Days 1, 15 Cylces 2 and 3. Isatuximab 10mg/kg Day 1, Cylces 4-39. Lenalidomide 10mg PO Days 1-28 Cylces 1-3 (all cycles 28 days) Lenalidomide 15mg PO Days 1-28 Cycle 4 and can continue until disease progression.

Interventions

Drug: - Isatuximab

Isatuximab 10mg/kg IV Days 1,8, 15, 22 Cycle 1 (all cycles 28 days). Isatuximab 10mg/kg Days 1, 15 Cylces 2 and 3. Isatuximab 10mg/kg Day 1, Cylces 4-39.

Drug: - Lenalidomide

Lenalidomide 15mg PO Days 1-28 Cycle 4 and can continue until disease progression.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

University of Illinois at Chicago, Chicago, Illinois

Status

Recruiting

Address

University of Illinois at Chicago

Chicago, Illinois, 60612

Site Contact

Sweiss Karen, PharmD

ksweis2@uic.edu

312-996-0875