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Tadalafil and Lenalidomide with or without Activated Marrow Infiltrating Lymphocytes in Treating Patients with High-Risk Multiple Myeloma Undergoing Stem Cell Transplant

Trial Status: Active

This randomized phase II trial studies how well tadalafil and lenalidomide with or without activated marrow infiltrating lymphocytes work in treating patients with multiple myeloma undergoing stem cell transplant. Activated marrow infiltrating lymphocytes are blood and bone marrow cells that are stimulated to react to certain proteins and may help to target and kill cancer cells. Tadalafil may increase the possibility of trafficking activated marrow infiltrating lymphocytes to the cancer site. Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. It is not yet known whether giving tadalafil and lenalidomide is more effective with or without activated marrow infiltrating lymphocytes in treating patients with multiple myeloma.

Inclusion Criteria

  • Previous diagnosis of multiple myeloma based on standard criteria; tests need not be performed within 30 days of registration
  • Active myeloma as defined as the presence of calcium, renal failure, anemia and bone (CRAB) criteria: hypercalcemia, renal insufficiency, anemia and/or bone disease
  • Measurable serum and/or urine M-protein from prior to induction therapy documented and available; a positive serum free lite assay is acceptable
  • Presence of at least one of the features defining high risk; these include: * High risk chromosomal translocations by fluorescence in situ hybridization (FISH): t(4;14), t(14;16), t(14;20), deletion (del)(17p), del(1p), amplification 1q * Myeloma Prognostic Risk Signature (MyPRS) gene expression profiling (GEP)-70 high risk signature either from diagnosis or at time of registration for the study * Lactate dehydrogenase (LDH) > 300 U/L at diagnosis * Relapse from prior therapy within 12 months
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Life expectancy >= 6 months
  • Corrected serum calcium < 11 mg/dL, and no evidence of symptomatic hypercalcemia; (corrected serum calcium is calculated by adding 0.8 mg/dL to the measured serum calcium for every 1 g/dL that the serum albumin falls below 4.0 g/dL)
  • Serum total bilirubin =< 2.0 times the upper limit of normal
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.0 times the upper limit of normal
  • Serum creatinine < 2.0 mg/dL
  • The patient must be able to comprehend and have signed the informed consent
  • Myeloma specific therapy with a minimum of 3 cycles
  • Achieved at least a partial response (PR) to therapy
  • Institutional criteria for and have institutional approval to undergo autologous peripheral blood stem cell transplantation
  • Females of child-bearing potential must have a negative serum beta human chorionic gonadotropin (HCG) test and be willing to use effective contraception (i.e. a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, or condom with spermicide, or abstinence) up to day 180

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 * Human T-cell lymphotrophic virus (HTLV)1/HTLV2 positive
  • Diagnosis of amyloidosis
  • Previous hematopoietic stem cell transplantation; patients can have had prior relapsed disease as long as they have never been previously transplanted
  • Known history of human immunodeficiency virus (HIV) infection
  • Use of corticosteroids (glucocorticoids) within 21 days of the MILs collection
  • Use of any myeloma-specific therapy within 21 days of the MILs collection
  • Systemic infection requiring treatment with antibiotics, antifungal, or antiviral agents within seven days of registration
  • Patients should be excluded if they are known to be positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (hepatitis C virus [HCV] antibody) indicating acute or chronic infection
  • Participation in any clinical trial, within four weeks prior to 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 erythematosus) requiring active systemic treatment; hypothyroidism without evidence of Graves' disease or Hashimoto’s thyroiditis is permitted
  • Known contraindication to phosphodiesterase-5 inhibitors (e.g. currently on nitrates)
  • Evidence of spinal cord compression
  • Major organ system dysfunction including (but not limited to): New York Heart Association class III or IV, pulmonary disease requiring the use of inhaled steroids or bronchodilators, renal, hepatic, gastrointestinal, neurologic, or psychiatric dysfunction which would impair patient’s ability to participate in the trial
  • HIV infection


Mayo Clinic in Florida
Status: ACTIVE
Contact: Sikander Ailawadhi
Phone: 904-953-7290
Moffitt Cancer Center
Status: ACTIVE
Contact: Frederick Lundry Locke
Phone: 813-745-2557


Johns Hopkins University / Sidney Kimmel Cancer Center
Status: ACTIVE
Contact: Philip Hollingsworth Imus
Phone: 410-955-8873


I. Determine the progression free survival (PFS) of autologous stem cell transplant (ASCT) alone versus (vs) ASCT plus marrow infiltrating lymphocytes (MILs).


I. Evaluate toxicity.

II. Evaluate overall survival.

III. Determine immune responses.

IV. Anti-tumor immune responses.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive melphalan intravenously (IV) over 20-30 minutes on days -2 and -1 and undergo ASCT on day 0. Patients then receive tadalafil orally (PO) on days 2-11 and activated marrow infiltrating lymphocytes IV on days 3 and 4. Patients also receive lenalidomide PO beginning on day 60 and continue in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive melphalan IV over 20-30 minutes on days -2 and -1 and undergo ASCT on day 0. Patients then receive tadalafil PO on days 2-11. Patients also receive lenalidomide PO beginning on day 60 and continuing in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at days 28, 60, 180, and 360, and then every 3 months for 4 years.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Johns Hopkins University / Sidney Kimmel Cancer Center

Principal Investigator
Philip Hollingsworth Imus

  • Primary ID J1343
  • Secondary IDs NCI-2013-01767, NA_00084466
  • ID NCT01858558