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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02728102
Recruitment Status : Active, not recruiting
First Posted : April 5, 2016
Last Update Posted : January 18, 2020
Sponsor:
Collaborators:
Blood and Marrow Transplant Clinical Trials Network
National Cancer Institute (NCI)
National Marrow Donor Program
Information provided by (Responsible Party):
National Heart, Lung, and Blood Institute (NHLBI)

Tracking Information
First Submitted Date  ICMJE March 30, 2016
First Posted Date  ICMJE April 5, 2016
Last Update Posted Date January 18, 2020
Actual Study Start Date  ICMJE July 2016
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 30, 2016)
Complete Response [ Time Frame: 1 year ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 27, 2016)
  • Response to treatment [ Time Frame: 6 months, 1 year, and 2 years ]
    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.
  • Myeloma Progression [ Time Frame: 6 months, 1 year, and 2 years ]
    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.
  • Minimal Residual Disease (MRD) Assessment [ Time Frame: 6 months, 1 year, and 2 years ]
    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.
  • Treatment-related Mortality (TRM) [ Time Frame: 2 years ]
    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.
  • Incidence of Toxicities [ Time Frame: 2 years ]
    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.
  • Incidence of Infections [ Time Frame: 2years ]
    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.
  • Progression-free survival [ Time Frame: 2 years ]
    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.
  • Overall Survival [ Time Frame: 2 years ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 30, 2016)
  • Response to treatment [ Time Frame: 6 months, 1 year, and 2 years ]
    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.
  • Myeloma Progression [ Time Frame: 6 months, 1 year, and 2 years ]
    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.
  • Minimal Residual Disease (MRD) Assessment [ Time Frame: 6 months, 1 year, and 2 years ]
    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.
  • Treatment-related Mortality (TRM) [ Time Frame: 2 years ]
    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.
  • Incidence of Toxicities [ Time Frame: 2 years ]
    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.
  • Incidence of Infections [ Time Frame: 2years ]
    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.
  • Progression-free survival [ Time Frame: 2 years ]
    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 combinedfrom time of randomization. A secondary pairwise analysis will compare progression-free survival between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm.
  • Overall Survival [ Time Frame: 2 years ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dendritic Cell/Myeloma Fusion Vaccine for Multiple Myeloma (BMT CTN 1401)
Official Title  ICMJE 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)
Brief 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).
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Procedure: Tumor Cell Collection
    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).
  • Procedure: Autologous Stem Cell Transplant
    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.
  • Drug: Melphalan
    Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices.
    Other Name: Alkeran
  • Procedure: Leukapheresis
    Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures.
  • Biological: Myeloma vaccine
    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.
    Other Names:
    • Dendritic cell fusion vaccine
    • DC/MM fusion vaccine
  • Drug: GM-CSF
    100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
    Other Names:
    • Granulocyte macrophage colony-stimulating factor
    • Leukine
  • Drug: Lenalidomide
    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.
    Other Name: Revlimid™
Study Arms  ICMJE
  • Experimental: Lenalidomide, vaccine, and GM-CSF
    Patients 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.
    Interventions:
    • Procedure: Tumor Cell Collection
    • Procedure: Autologous Stem Cell Transplant
    • Drug: Melphalan
    • Procedure: Leukapheresis
    • Biological: Myeloma vaccine
    • Drug: GM-CSF
    • Drug: Lenalidomide
  • Active Comparator: Lenalidomide and GM-CSF
    Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF.
    Interventions:
    • Procedure: Tumor Cell Collection
    • Procedure: Autologous Stem Cell Transplant
    • Drug: Melphalan
    • Drug: GM-CSF
    • Drug: Lenalidomide
  • Active Comparator: Maintenance Lenalidomide
    Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.
    Interventions:
    • Procedure: Tumor Cell Collection
    • Procedure: Autologous Stem Cell Transplant
    • Drug: Melphalan
    • Drug: Lenalidomide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 7, 2019)
203
Original Estimated Enrollment  ICMJE
 (submitted: March 30, 2016)
188
Estimated Study Completion Date  ICMJE August 2022
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02728102
Other Study ID Numbers  ICMJE BMTCTN1401
U01HL069294 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Results will be published in a manuscript and supporting information submitted to NIH BioLINCC (including data dictionaries, case report forms, data submission documentation, documentation for outcomes dataset, etc where indicated).
Supporting Materials: Study Protocol
Supporting Materials: Informed Consent Form (ICF)
Time Frame: Within 6 months of official study closure at participating sites.
Access Criteria: Available to the public
URL: https://biolincc.nhlbi.nih.gov/home/
Responsible Party National Heart, Lung, and Blood Institute (NHLBI)
Study Sponsor  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Collaborators  ICMJE
  • Blood and Marrow Transplant Clinical Trials Network
  • National Cancer Institute (NCI)
  • National Marrow Donor Program
Investigators  ICMJE
Study Director: Mary Horowitz, MD Center for International Blood and Marrow Transplant Research
PRS Account National Heart, Lung, and Blood Institute (NHLBI)
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP