Dendritic Cell/Myeloma Fusion Vaccine for Multiple Myeloma (BMT CTN 1401)
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Tumor Cell Collection; Autologous Stem Cell Transplant; Melphalan; Leukapheresis; Myeloma vaccine; GM-CSF; Lenalidomide
Intervention description: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).; Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation.; Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices.; Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures.; The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients who have <3 x 10^6 total fusion cells will not proceed with vaccination. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. Vaccine will be administered by subcutaneous injection in the upper thigh.; 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.; Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Intervention MeSH terms: Lenalidomide; Melphalan; Molgramostim; Vaccines; Sargramostim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 203.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Multiple Myeloma; Lenalidomide; Maintenance Therapy; Hematologic Disorders; Vaccine; GM-CSF; Transplant; Anti-Myeloma Agents

Summary:

      The study is designed as a Phase II, multicenter trial of vaccination with Dendritic
      cell/myeloma fusions with granulocyte macrophage colony-stimulating factor (GM-CSF) adjuvant
      plus lenalidomide maintenance therapy versus maintenance therapy alone or with GM-CSF
      following autologous transplant as part of upfront treatment of multiple myeloma (MM). It is
      hypothesized that the dendritic cell myeloma vaccine will result in improved response in
      patients with multiple myeloma after autologous Hematopoietic Cell Transplant (HCT).
    

Eligibility criteria:

        Initial Inclusion Criteria:

          1. Patients must be considered transplant eligible by the treating physician at time of
             study entry.

          2. Patients must meet the criteria for symptomatic multiple myeloma prior to initiating
             systemic anti-myeloma treatment.

          3. Age >18 years and ≤ 70 years at the time of enrollment

          4. Karnofsky Performance status of ≥ 70%

          5. Patients must have > 20% plasma cells in the bone marrow aspirate differential <60
             days prior to enrollment. The required bone marrow evaluation will need to be repeated
             for patients who received more than 1 cycle of anti-myeloma therapy (corticosteroid
             with or without other anti-myeloma agents)

          6. Patients must have received ≤ 1 cycles of systemic anti-myeloma therapy.

          7. Renal: Creatinine clearance of ≥ 40 mL/min, estimated or calculated.

        Initial Exclusion Criteria:

          1. Patients with a prior autologous or allogeneic HCT

          2. Patients with purely non-secretory MM [absence of a monoclonal protein (M protein) in
             serum as measured by electrophoresis and immunofixation and the absence of Bence Jones
             protein in the urine defined by use of conventional electrophoresis and immunofixation
             techniques and the absence of involved serum free light chain >100 mg/L]. Patients
             with light chain MM detected in the serum by free light chain assay are eligible.

          3. Patients with Plasma Cell Leukemia

          4. Patients with disease progression prior to enrollment

          5. Patients seropositive for the human immunodeficiency virus (HIV).

          6. Myocardial infarction within 6 months prior to enrollment or New York Heart
             Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
             uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities. Prior to study entry, any ECG
             abnormality at screening will be documented by the investigator as not medically
             relevant.

          7. Patients with active clinically significant autoimmune disease, defined as a history
             of requiring systemic immunosuppressive therapy and at ongoing risk for potential
             disease exacerbation. Patients with a history of autoimmune thyroid disease, asthma,
             or limited skin manifestations are potentially eligible.

          8. Patients receiving other investigational immunotherapy or anti-myeloma drugs within 14
             days before enrollment.

          9. Patients with prior malignancies except resected basal cell carcinoma or treated
             cervical carcinoma in situ. Cancer treated with curative intent < 5 years prior to
             enrollment will not be allowed unless approved by the Protocol Officer or one of the
             Protocol Chairs. Cancer treated with curative intent > 5 years prior to enrollment is
             allowed.

         10. Female patients who are pregnant (positive beta-HCG) or breastfeeding.

         11. Females of childbearing potential (FCBP) or men who have sexual contact with FCBP
             unwilling to use contraceptive techniques (Appendix D) during the length of
             lenalidomide maintenance therapy.

         12. Patients who have received mid-intensity melphalan (>50 mg IV) as part of prior
             therapy.

         13. Prior organ transplant requiring immunosuppressive therapy.

         14. Patients who previously received lenalidomide and have experienced toxicities
             resulting in treatment discontinuation.

         15. Patients who experienced thromboembolic events while on full anticoagulation during
             prior therapy with lenalidomide or thalidomide.

         16. Patients unwilling to take deep vein thrombosis (DVT) prophylaxis.

         17. Patients unable or unwilling to provide informed consent.

         18. Patients unable or unwilling to return to the transplant center for their assigned
             treatments.

        Randomization Inclusion Criteria:

          1. Patient received transplant < 12 months of enrollment onto BMT CTN 1401.

          2. No disease progression since initiation of systemic anti-myeloma therapy as determined
             within seven days of randomization/enrollment.

          3. Received an autologous cell transplant with melphalan 200mg/m^2 with a minimum cell
             dose of 2x10^6 CD34+ cells/kg (actual body weight).

          4. Mucositis and gastrointestinal symptoms resolved, off hyperalimentation and
             intravenous hydration.

          5. No evidence of uncontrolled infection requiring systemic therapy. Patients who
             completed treatment for an infection but are continuing antibiotics, anti-viral, or
             anti-fungal therapy for prophylaxis are eligible to continue on protocol.

          6. Platelet count ≥75,000/mm^3 (without transfusion in previous 7 days).

          7. Absolute neutrophil count (ANC) ≥ 1,500/mm^3 without filgrastim administration within
             7 days, or pegfilgrastim within 14 days of measurement.

          8. Hepatic: bilirubin < 2x the upper limit of normal and alanine aminotransferase (ALT)
             and aspartate aminotransferase (AST) < 2.5x the upper limit of normal. (Patients who
             have been diagnosed with Gilbert's Disease are allowed to exceed the defined bilirubin
             value of 2x the upper limit of normal)

          9. Renal: Creatinine clearance of ≥ 40 mL/min, estimated or calculated. Patients with
             creatinine clearance ≥30 but <40 will be considered with review/approval from the
             protocol chairs or officer if the cause of renal insufficiency is associated with
             multiple myeloma.

         10. All study participants must be registered into the mandatory Revlimid REMs program,
             and be willing and able to comply with the requirements.

         11. Females of childbearing potential (FCBP) as defined in section 2.7.1.1 must have a
             negative serum pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14
             days prior to and again within 24 hours of prescribing lenalidomide (prescriptions
             must be filled within 7 days)

         12. FCBP must either commit to abstain continuously from sexual intercourse or use TWO
             acceptable methods of birth control, one highly effective method and one additional
             effective method AT THE SAME TIME, at least 4 weeks before she starts taking
             lenalidomide, during therapy, during dose interruptions, and continuing for 4 weeks
             following discontinuation of lenalidomide.

         13. FCBP must agree to ongoing pregnancy testing as required by the Revlimid REMs program.

         14. Men must agree to use a latex condom during sexual contact with females of child
             bearing potential even if they have had a successful vasectomy while taking
             lenalidomide, during dose interruptions and for 28 days after discontinuing
             lenalidomide.

         15. Patients must be willing to receive DVT prophylaxis.