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Trial record 3 of 2156 for:    myeloma

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by National Heart, Lung, and Blood Institute (NHLBI)
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)
ClinicalTrials.gov Identifier:
NCT02728102
First received: March 30, 2016
Last updated: September 28, 2016
Last verified: September 2016
  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).

Condition Intervention Phase
Multiple Myeloma
Procedure: Tumor Cell Collection
Procedure: Autologous Stem Cell Transplant
Drug: Melphalan
Procedure: Leukapheresis
Biological: Myeloma vaccine
Drug: GM-CSF
Drug: Lenalidomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:
  • Complete Response [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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:
  • Response to treatment [ Time Frame: 6 months, 1 year, and 2 years ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 188
Study Start Date: July 2016
Estimated Study Completion Date: August 2022
Estimated Primary Completion Date: August 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
Three doses of 3 x 10^6 fusion cells will be prepared. A minimum of 2 doses will be required to proceed with treatment. 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™
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.
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
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™
Active Comparator: Maintenance Lenalidomide
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.
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
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™

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 at a day 60 +/- 7 days 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.
  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 < 2 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 High-Risk Multiple Myeloma. High-risk is defined by the presence of any one of the following: deletion of chromosome 13 by conventional cytogenetics, hypodiploidy, abnormality in chromosome 1(1q amplification or 1p deletion), t(4;14), t(14;16), t(14;20) or deletion of 17p by fluorescence in situ hybridization (FISH) or conventional karyotyping; high-risk criteria based on commercially available gene expression profiling (GEP) detected at any time prior to enrollment;
  5. Patients with disease progression prior to enrollment
  6. Patients seropositive for the human immunodeficiency virus (HIV).
  7. 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.
  8. 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.
  9. Patients receiving other investigational immunotherapy or anti-myeloma drugs within 14 days before enrollment.
  10. 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.
  11. Female patients who are pregnant (positive beta-HCG) or breastfeeding.
  12. 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.
  13. Patients who have received mid-intensity melphalan (>50 mg IV) as part of prior therapy.
  14. Prior organ transplant requiring immunosuppressive therapy.
  15. Patients who previously received lenalidomide and have experienced toxicities resulting in treatment discontinuation.
  16. Patients who experienced thromboembolic events while on full anticoagulation during prior therapy with lenalidomide or thalidomide.
  17. Patients unwilling to take deep vein thrombosis (DVT) prophylaxis.
  18. Patients unable or unwilling to provide informed consent.
  19. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02728102

Contacts
Contact: Heather Wittsack hwittsack@emmes.com
Contact: Adam Mendizabal, PhD amendizabal@emmes.com

Locations
United States, Georgia
Emory University Not yet recruiting
Atlanta, Georgia, United States, 30322
Contact: Ajay Nooka, MD       anooka@emory.edu   
United States, Maryland
University of Maryland/Greenebaum Cancer Center Recruiting
Baltimore, Maryland, United States, 21201
Contact: Aaron Rapaport, MD       arapoport@umm.edu   
United States, Massachusetts
Beth Israel Deaconess Medical Center/Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: David Avigan, MD       davigan@bidmc.harvard.edu   
United States, Minnesota
University of Minnesota Not yet recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Mukta Arora, MD       arora005@umn.edu   
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198-7680
Contact: Julie Vose, MD       jmvose@unmc.edu   
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Philip McCarthy, MD       Philip.mccarthy@roswellpark.org   
Mount Sinai Medical Center Recruiting
New York, New York, United States, 10029
Contact: Keren Osman, MD       keren.osman@mountsinai.org   
Memorial Sloan-Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
Contact: David Chung, MD       ChungD1@MSKCC.ORG   
United States, Ohio
University Hospitals of Cleveland/Case Western Recruiting
Cleveland, Ohio, United States, 44106
Contact: Hillard Lazarus, MD       hillard.lazarus@case.edu   
Ohio State University/Arthur G. James Cancer Hospital Recruiting
Columbus, Ohio, United States, 43210
Contact: Yvonne Efebera, MD       Yvonne.Efebera@osumc.edu   
United States, Pennsylvania
University of Pennsylvania Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Edward Stadtmauer, MD       Edward.Stadtmauer@uphs.upenn.edu   
United States, Texas
Baylor University Medical Center Recruiting
Dallas, Texas, United States, 75246
Contact: Joseph Fay, MD       josephf@BaylorHealth.edu   
University of Texas/MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Nina Shah, MD       nshah@mdanderson.org   
United States, Washington
Fred Hutchinson Cancer Research Center Not yet recruiting
Seattle, Washington, United States, 98109-1024
Contact: Leona Holmberg, MD       lholmber@fredhutch.org   
United States, Wisconsin
University of Wisconsin Hospital & Clinics Not yet recruiting
Madison, Wisconsin, United States, 53792
Contact: Natalie Callendar       nsc@medicine.wisc.edu   
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53211
Contact: Marcelo Pasquini, MD       mpasquini@mcw.edu   
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Blood and Marrow Transplant Clinical Trials Network
National Cancer Institute (NCI)
National Marrow Donor Program
Investigators
Study Director: Mary Horowitz, MD Center for International Blood and Marrow Transplant Research
  More Information

Additional Information:
Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT02728102     History of Changes
Other Study ID Numbers: BMTCTN1401  U01HL069294 
Study First Received: March 30, 2016
Last Updated: September 28, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Findings will be published in a manuscript

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):
Multiple Myeloma
Lenalidomide
Maintenance Therapy
Hematologic Disorders
Vaccine
GM-CSF
Transplant
Anti-Myeloma Agents

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
Vaccines
Lenalidomide
Thalidomide
Melphalan
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on September 29, 2016