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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Biological: aMIL; Drug: No aMIL	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 2013
• Actual Primary Completion Date: June 19, 2019
• Actual Study Completion Date: June 19, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: aMIL Arm; Patients receive activated Marrow Infiltrating Lymphocytes (aMIL)	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.
Active Comparator: No aMIL; Patients do not receive activated Marrow Infiltrating Lymphocytes (aMIL)	Drug: No aMIL; On day 0, patients will receive auto transplant followed by Tadalafil. At day 60, patients will receive Lenalidomide.

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. Overall Survival (OS) [ Time Frame: 3 years ]
   OS assessed by number of participants alive at the end of follow up period.
3. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Locations

United States, Maryland

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States, 21231

Sponsors and Collaborators

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

The Leukemia and Lymphoma Society

Investigators

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

  Study Documents (Full-Text)

Documents provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:

Study Protocol and Statistical Analysis Plan  [PDF] January 15, 2020

More Information

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT01858558
• Other Study ID Numbers: J1343; NA_00084466 ( Other Identifier: JHMIRB )
• First Posted: May 21, 2013
• Results First Posted: June 29, 2020
• Last Update Posted: June 29, 2020
• Last Verified: June 2020

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases