RECRUITING

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

Conditions

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a phase II study where patients will undergo isatuximab and lenalidomide maintenance if they are MRD-positive after Autologous Stem Cell Transplant (ASCT)

Official Title

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

Quick Facts

Study Start:2023-01-05

Study Completion:2030-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05344833

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 post -ASCT maintenance therapy. 4. Received up to or less than 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 180 days and have not yet initiated post-ASCT maintenance. 6. Obtain at least partial response according to IMWG criteria prior to autologous stem cell transplant 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. 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. 12. Patients must be willing to take appropriate DVT prophylaxis, either aspirin, low molecular weight heparin, direct oral anticoagulants, or warfarin while receiving lenalidomide.	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. Prior intolerance to isatuximab or lenalidomide. 3. Prior allogeneic stem cell transplant. 4. Prior solid organ transplant requiring immunosuppressive therapy. 5. 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. 6. 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. 7. Treatment with any investigational drug within 30 days prior to enrollment. 8. Planned transplant is considered part of tandem autologous transplant approach for newly diagnosed MM. 9. 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. 10. 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. 11. 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. 12. 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). 13. 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.

Inclusion Criteria

Exclusion 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 post -ASCT maintenance therapy.
4. Received up to or less than 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 180 days and have not yet initiated post-ASCT maintenance.
6. Obtain at least partial response according to IMWG criteria prior to autologous stem cell transplant
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.
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.
12. Patients must be willing to take appropriate DVT prophylaxis, either aspirin, low molecular weight heparin, direct oral anticoagulants, or warfarin while receiving lenalidomide.

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. Prior intolerance to isatuximab or lenalidomide.
3. Prior allogeneic stem cell transplant.
4. Prior solid organ transplant requiring immunosuppressive therapy.
5. 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.
6. 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.
7. Treatment with any investigational drug within 30 days prior to enrollment.
8. Planned transplant is considered part of tandem autologous transplant approach for newly diagnosed MM.
9. 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.
10. 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.
11. 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.
12. 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).
13. 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.

Contacts and Locations

Study Contact

Karen Sweiss, PhD

CONTACT

312-996-0875

ksweis2@uic.edu

Study Locations (Sites)

University of Illinois at Chicago

Chicago, Illinois, 60612

United States

Collaborators and Investigators

Sponsor: University of Illinois at Chicago

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-01-05

Study Completion Date2030-12

Study Record Updates

Study Start Date2023-01-05

Study Completion Date2030-12

Terms related to this study

Additional Relevant MeSH Terms

Multiple Myeloma