Tadalafil and Lenalidomide Maintenance With or Without Activated Marrow Infiltrating Lymphocytes (MILs) in High Risk Myeloma

Study Overview
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Brief Summary
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This research is being done to find out if altering the immune system by giving activated marrow infiltrating lymphocytes (MILs) can improve outcomes for multiple myeloma patients who receive a standard autologous stem cell transplant.

Official Title
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Randomized Phase II Study of Autologous Stem Cell Transplantation With Tadalafil and Lenalidomide Maintenance With or Without Activated Marrow Infiltrating Lymphocytes (MILs) in High Risk Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Biological: aMIL
* Drug: No aMIL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 - 80 years old; Patients with active myeloma requiring systemic treatment; Newly diagnosed patients. Relapsed myeloma patients that have not previously had a transplant; Meeting criteria for high-risk disease; Measurable serum and/or urine M-protein from prior to induction therapy documented and available. A positive serum free lite assay is acceptable; Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 (see Appendix C). Meet all institutional requirements for autologous stem cell transplantation; The patient must be able to comprehend and have signed the informed consent; Patients must have had > than PR after last therapy. Exclusion Criteria: Diagnosis of any of the following cancers: POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein] and skin changes); Non-secretory myeloma (no measurable protein on Serum Free Lite Assay); Plasma cell leukemia; Diagnosis of amyloidosis; Failed to achieve at least a partial response (PR) to latest therapy; Previous hematopoietic stem cell transplantation;Patients can have had prior relapsed disease as long as they have never been previously transplanted; Known history of HIV infection; Use of corticosteroids (glucocorticoids) within 21 days of bone marrow collection; Use of any myeloma-specific therapy within 21 days of bone marrow collection; Infection requiring treatment with antibiotics, antifungal, or antiviral agents within seven days of registration; Participation in any clinical trial within 28 days of registration on this trial, which involved an investigational drug or device; History of malignancy other than multiple myeloma within five years of registration, except adequately treated basal or squamous cell skin cancer; Active autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosis) requiring active systemic treatment. Hypothyroidism without evidence of Grave's disease or Hashimoto's thyroiditis is permitted. Human T-lymphotropic virus (HTLV) 1 or 2 positive; Known hypersensitivity to Prevnar or any of its components; Contraindication to phosphodiesterase-5 inhibitors (e.g. currently on nitrates).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: aMIL Arm<br>Patients receive activated Marrow Infiltrating Lymphocytes (aMIL) | Biological: aMIL<br>* On day 0, patients will receive auto transplant followed by Tadalafil and aMIL. At day 60, patients will receive Lenalidomide.<br>Drug: No aMIL<br>* On day 0, patients will receive auto transplant followed by Tadalafil. At day 60, patients will receive Lenalidomide.<br>|
| Active Comparator: No aMIL<br>Patients do not receive activated Marrow Infiltrating Lymphocytes (aMIL) | Drug: No aMIL<br>* On day 0, patients will receive auto transplant followed by Tadalafil. At day 60, patients will receive Lenalidomide.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of MILs as Assessed by the Ability to Harvest, Expand, and Infuse the MILs Product | Feasibility is defined as the ability to harvest, expand, and infuse the MILs product within 120 days. After treating 60 patients with MILs, we will declare MILs not feasible if we can only harvest, expand, and deliver MILs to 40 or fewer patients. | 120 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity as Determined by Total Number of Grade 3 or Higher Adverse Events | Total number of adverse events grade 3 or higher that occur from MILs harvest through 60 days after transplant. | 60 days from aMILs harvest until day 60 after transplant | 
| Overall Survival (OS) | OS assessed by number of participants alive at the end of follow up period. | 3 years | 
| Progression-free Survival (PFS) | Median PFS time equals the time of randomization (in months) until disease progression, death from any cause, or protocol deviation due to lenalidomide dosing (above 10mg), whichever occurs first. | 5 years |