Clinical Trials /

Dendritic Cell/Myeloma Fusion Vaccine for Multiple Myeloma (BMT CTN 1401)

NCT02728102

Description:

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).

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Dendritic Cell/Myeloma Fusion Vaccine for Multiple Myeloma (BMT CTN 1401)
  • Official Title: Phase II Multicenter Trial of Single Autologous Hematopoietic Cell Transplant Followed by Lenalidomide Maintenance for Multiple Myeloma With or Without Vaccination With Dendritic Cell/Myeloma Fusions (BMT CTN #1401)

Clinical Trial IDs

  • ORG STUDY ID: BMTCTN1401
  • SECONDARY ID: U01HL069294
  • NCT ID: NCT02728102

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
MelphalanAlkeranLenalidomide, vaccine, and GM-CSF
Myeloma vaccineDendritic cell fusion vaccine, DC/MM fusion vaccineLenalidomide, vaccine, and GM-CSF
GM-CSFGranulocyte macrophage colony-stimulating factor, LeukineLenalidomide, vaccine, and GM-CSF
LenalidomideRevlimidLenalidomide, vaccine, and GM-CSF

Purpose

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).

Detailed Description

      The study is a three-arm, phase II randomized, open-labeled clinical trial that randomizes
      patients to vaccination with Dendritic Cell (DC)/myeloma fusions/GM-CSF plus lenalidomide
      maintenance therapy or lenalidomide maintenance therapy with or without GM-CSF following
      autologous transplant as part of upfront treatment for patients diagnosed with multiple
      myeloma. Patients are randomized approximately 2 months post transplant and will begin
      maintenance lenalidomide between day 90 and 100. The primary objective of this randomized
      trial is to compare the proportion of patients alive and in complete response (defined as CR
      or sCR) at one year post transplant between patients receiving DC/myeloma vaccine/GM-CSF with
      lenalidomide maintenance therapy to those receiving lenalidomide maintenance therapy with or
      without GM-CSF.
    

Trial Arms

NameTypeDescriptionInterventions
Lenalidomide, vaccine, and GM-CSFExperimentalPatients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF.
  • Melphalan
  • Myeloma vaccine
  • GM-CSF
  • Lenalidomide
Lenalidomide and GM-CSFActive ComparatorPatients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF.
  • Melphalan
  • GM-CSF
  • Lenalidomide
Maintenance LenalidomideActive ComparatorPatients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.
  • Melphalan
  • Lenalidomide

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.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete Response
Time Frame:1 year
Safety Issue:
Description:The primary objective of this randomized trial is to compare the proportion of patients alive and in complete response (CR or sCR) at one year post transplant between patients receiving DC/myeloma vaccine/GM-CSF with lenalidomide maintenance therapy to those receiving lenalidomide maintenance therapy with or without GM-CSF.

Secondary Outcome Measures

Measure:Response to treatment
Time Frame:6 months, 1 year, and 2 years
Safety Issue:
Description:The trial will assess the rates of VGPR or better (VGPR, nCR, CR and sCR) responses) according to the International Uniform Response Criteria. A secondary pairwise analysis will compare the CR rates at 1 year between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm.
Measure:Myeloma Progression
Time Frame:6 months, 1 year, and 2 years
Safety Issue:
Description:The cumulative incidence of myeloma progression will be compared between vaccine and no-vaccine arms combined. A secondary pairwise analysis will compare the cumulative incidence of myeloma progression between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm.
Measure:Minimal Residual Disease (MRD) Assessment
Time Frame:6 months, 1 year, and 2 years
Safety Issue:
Description:MRD is defined as the presence of malignant plasma cells detected by multicolor flow cytometry among patients who are in complete remission. The proportion of patients who are MRD negative at one year will be compared between vaccine and no-vaccine arms combined. A secondary pairwise analysis will be conducted comparing the proportion of patients who are MRD negative at one year between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm.
Measure:Treatment-related Mortality (TRM)
Time Frame:2 years
Safety Issue:
Description:TRM is defined as death occurring in a patient from causes other than disease relapse or progression. TRM from time of randomization will be compared between vaccine and no-vaccine arms combined. A secondary pairwise analysis will compare TRM between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm.
Measure:Incidence of Toxicities
Time Frame:2 years
Safety Issue:
Description:The proportion of patients developing Grade ≥ 3 toxicity will be compared between the vaccine and no-vaccine arms combined until disease progression or end of follow up. A secondary pairwise analysis will compare the incidence of toxicities between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm.
Measure:Incidence of Infections
Time Frame:2years
Safety Issue:
Description:The incidence of definite and probable viral, fungal and bacterial infections will be tabulated for each patient. The proportion of patients in each treatment arm with these infections will be compared from randomization until disease progression or end of follow up.
Measure:Progression-free survival
Time Frame:2 years
Safety Issue:
Description:Patients are considered a failure of this endpoint if they die or suffer from disease progression. The time to this event is the time from randomization to progression, death, initiation of non-protocol anti myeloma therapy, loss to follow up or end of study whichever comes first and it will be compared between the vaccine and no-vaccine arms combined from time of randomization. A secondary pairwise analysis will compare progression-free survival between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm.
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:Patients are considered a failure of this endpoint if they die. The time to this event is the time from randomization to death, loss to follow-up or the end of the study, whichever comes first. Patients alive at the time of last observation are considered censored. Overall survival will be compared between the vaccine and no-vaccine arms combined from time of randomization. A secondary pairwise analysis will compare overall survival between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:National Heart, Lung, and Blood Institute (NHLBI)

Trial Keywords

  • Multiple Myeloma
  • Lenalidomide
  • Maintenance Therapy
  • Hematologic Disorders
  • Vaccine
  • GM-CSF
  • Transplant
  • Anti-Myeloma Agents

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