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

• ClinicalTrials.gov Identifier: NCT01858558
• Recruitment Status: Completed
• First Posted: May 21, 2013
• Results First Posted: June 29, 2020
• Last Update Posted: June 29, 2020
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborator: The Leukemia and Lymphoma Society
• Information provided by (Responsible Party): Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information

• First Submitted Date: May 14, 2013
• First Posted Date: May 21, 2013
• Results First Submitted Date: June 11, 2020
• Results First Posted Date: June 29, 2020
• Last Update Posted Date: June 29, 2020
• Actual Study Start Date: September 2013
• Actual Primary Completion Date: June 19, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 11, 2020)

Feasibility of MILs as Assessed by the Ability to Harvest, Expand, and Infuse the MILs Product [ Time Frame: 120 days ]

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.

Original Primary Outcome Measures (submitted: May 16, 2013)

Progression free survival [ Time Frame: 2 years ]

Determine the efficacy of Activated Marrow Infiltrating Lymphocytes (aMILS) in prolonging progression free survival (PFS) in patients with high risk multiple myeloma followed by Autologous Stem Cell Transplantation (ASCT).

Current Secondary Outcome Measures (submitted: June 11, 2020)

• Toxicity as Determined by Total Number of Grade 3 or Higher Adverse Events [ Time Frame: 60 days from aMILs harvest until day 60 after transplant ]
  Total number of adverse events grade 3 or higher that occur from MILs harvest through 60 days after transplant.
• Overall Survival (OS) [ Time Frame: 3 years ]
  OS assessed by number of participants alive at the end of follow up period.
• Progression-free Survival (PFS) [ Time Frame: 5 years ]
  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.

Original Secondary Outcome Measures (submitted: May 16, 2013)

• Toxicity [ Time Frame: 1 year ]
  Adverse events related to the infusion of aMILs will be collected.
• Overall Survival [ Time Frame: 1 year ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Tadalafil and Lenalidomide Maintenance With or Without Activated Marrow Infiltrating Lymphocytes (MILs) in High Risk Myeloma
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Myeloma

Intervention

• Biological: aMIL
  On day 0, patients will receive auto transplant followed by Tadalafil and aMIL. At day 60, patients will receive Lenalidomide.
• Drug: No aMIL
  On day 0, patients will receive auto transplant followed by Tadalafil. At day 60, patients will receive Lenalidomide.

Study Arms

• Experimental: aMIL Arm
  Patients receive activated Marrow Infiltrating Lymphocytes (aMIL)
  Interventions:

  • Biological: aMIL
  • Drug: No aMIL
• Active Comparator: No aMIL
  Patients do not receive activated Marrow Infiltrating Lymphocytes (aMIL)
  Intervention: Drug: No aMIL

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 11, 2020): 102
• Original Estimated Enrollment (submitted: May 16, 2013): 90
• Actual Study Completion Date: June 19, 2019
• Actual Primary Completion Date: June 19, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01858558
• Other Study ID Numbers: J1343; NA_00084466 ( Other Identifier: JHMIRB )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Original Responsible Party: Same as current
• Current Study Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Original Study Sponsor: Same as current
• Collaborators: The Leukemia and Lymphoma Society

Investigators

• Principal Investigator: Philip Imus, M.D.; Johns Hopkins University

• PRS Account: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Verification Date: June 2020