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

NCT02728102 | Completed Phase 2 Results DMC

• 2 other identifiers: BMT CTN 1401U01HL069294
• Study Type: interventional
• Target: 203
• Locations: 1 country
• Sites: 15

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).

Conditions

Multiple Myeloma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With 1-year Response Rate of CR/sCR

  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. Complete Response (CR) is defined to require all the followings: Absence of the original monoclonal paraprotein in serum and urine by routine electrophoresis and by immunofixation; Less than 5% plasma cells in a bone marrow aspirate and also on trephine bone biopsy, if biopsy is performed; No increase in size or number of lytic bone lesions on radiological investigations; Disappearance of soft tissue plasmacytomas. Stringent Complete Response (sCR) is defined to require all the followings in addition to CR: Normal free light chain ratio (FLC); Absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.

  1 year

Secondary Outcomes (14)

• Participants Response to Treatment

  6 months, 1 year, and 2 years post-transplant and at Cycles 3(Day 57), 6(Day 141), 9(Day 225), 12(Day 309), 15 (Day 393), 18(Day 477), 21(Day 561) and 24(Day 654) of maintenance therapy

• Percentage of Participants With Myeloma Progression of Vaccine and Non-vaccine Arms

  2 years

• Percentage of Participants With Myeloma Progression in Pairwise Analysis

  2 years

• Percentage of Participants With Treatment-related Mortality (TRM)

  2 years

• Percentage of Participants With Progression-Free Survival

  2 years

Study Arms (3)

Lenalidomide, vaccine, and GM-CSF

EXPERIMENTAL

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; Procedure: Autologous Stem Cell Transplant; Drug: Melphalan; Procedure: Leukapheresis; Biological: Myeloma vaccine; Drug: GM-CSF; Drug: Lenalidomide

Lenalidomide and GM-CSF

ACTIVE COMPARATOR

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; Procedure: Autologous Stem Cell Transplant; Drug: Melphalan; Drug: GM-CSF; Drug: Lenalidomide

Maintenance Lenalidomide

ACTIVE COMPARATOR

Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.

Procedure: Tumor Cell Collection; Procedure: Autologous Stem Cell Transplant; Drug: Melphalan; Drug: Lenalidomide

Interventions

Tumor Cell Collection PROCEDURE

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).

Lenalidomide and GM-CSF; Lenalidomide, vaccine, and GM-CSF; Maintenance Lenalidomide

Autologous Stem Cell Transplant PROCEDURE

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.

Lenalidomide and GM-CSF; Lenalidomide, vaccine, and GM-CSF; Maintenance Lenalidomide

Melphalan DRUG

Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.

Also known as: Alkeran

Lenalidomide and GM-CSF; Lenalidomide, vaccine, and GM-CSF; Maintenance Lenalidomide

Leukapheresis PROCEDURE

Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures.

Lenalidomide, vaccine, and GM-CSF

Myeloma vaccine BIOLOGICAL

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.

Also known as: Dendritic cell fusion vaccine, DC/MM fusion vaccine

Lenalidomide, vaccine, and GM-CSF

GM-CSF DRUG

100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.

Also known as: Granulocyte macrophage colony-stimulating factor, Leukine

Lenalidomide and GM-CSF; Lenalidomide, vaccine, and GM-CSF

Lenalidomide DRUG

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.

Also known as: Revlimid™

Lenalidomide and GM-CSF; Lenalidomide, vaccine, and GM-CSF; Maintenance Lenalidomide

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be considered transplant eligible by the treating physician at time of study entry.
• Patients must meet the criteria for symptomatic multiple myeloma prior to initiating systemic anti-myeloma treatment.
• Age \>18 years and ≤ 70 years at the time of enrollment
• Karnofsky Performance status of ≥ 70%
• 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)
• Patients must have received ≤ 1 cycles of systemic anti-myeloma therapy.
• Renal: Creatinine clearance of ≥ 40 mL/min, estimated or calculated.

You may not qualify if:

• Patients with a prior autologous or allogeneic HCT
• 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.
• Patients with Plasma Cell Leukemia
• Patients with disease progression prior to enrollment
• Patients seropositive for the human immunodeficiency virus (HIV).
• 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.
• 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.
• Patients receiving other investigational immunotherapy or anti-myeloma drugs within 14 days before enrollment.
• 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.
• Female patients who are pregnant (positive beta-HCG) or breastfeeding.
• 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.
• Patients who have received mid-intensity melphalan (\>50 mg IV) as part of prior therapy.
• Prior organ transplant requiring immunosuppressive therapy.
• Patients who previously received lenalidomide and have experienced toxicities resulting in treatment discontinuation.
• Patients who experienced thromboembolic events while on full anticoagulation during prior therapy with lenalidomide or thalidomide.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead
• Blood and Marrow Transplant Clinical Trials Network: collaborator
• National Cancer Institute (NCI): collaborator
• National Marrow Donor Program: collaborator

Study Sites (15)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Beth Israel Deaconess Medical Center/Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198-7680, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

University Hospitals of Cleveland/Case Western

Cleveland, Ohio, 44106, United States

Location

Ohio State University/Arthur G. James Cancer Hospital

Columbus, Ohio, 43210, United States

Location

University of Texas/MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-1024, United States

Location

University of Wisconsin Hospital & Clinics

Madison, Wisconsin, 53792, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53211, United States

Location

Related Publications (1)

• Chung DJ, Shah N, Wu J, Logan B, Bisharat L, Callander N, Cheloni G, Anderson K, Chodon T, Dhakal B, Devine S, Somaiya Dutt P, Efebera Y, Geller N, Ghiasuddin H, Hematti P, Holmberg L, Howard A, Johnson B, Karagkouni D, Lazarus HM, Malek E, McCarthy P, McKenna D, Mendizabal A, Nooka A, Munshi N, O'Donnell L, Rapoport AP, Reese J, Rosenblatt J, Soiffer R, Stroopinsky D, Uhl L, Vlachos IS, Waller EK, Young JW, Pasquini MC, Avigan D. Randomized Phase II Trial of Dendritic Cell/Myeloma Fusion Vaccine with Lenalidomide Maintenance after Upfront Autologous Hematopoietic Cell Transplantation for Multiple Myeloma: BMT CTN 1401. Clin Cancer Res. 2023 Dec 1;29(23):4784-4796. doi: 10.1158/1078-0432.CCR-23-0235.

  PMID: 37463058 BACKGROUND

Related Links

• Blood and Marrow Transplant Clinical Trials Network

MeSH Terms

Conditions

Multiple Myeloma; Hematologic Diseases

Interventions

Melphalan; Leukapheresis; Granulocyte-Macrophage Colony-Stimulating Factor; Colony-Stimulating Factors; sargramostim; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Proteins; Biological Factors; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Adam Mendizabal, PhD
• Organization: The Emmes Company

amendizabal@emmes.com

301-284-1798

Study Officials

• Mary Horowitz, MD

  Center for International Blood and Marrow Transplant Research

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2016
• First Posted: April 5, 2016
• Study Start: July 1, 2016
• Primary Completion: June 30, 2020
• Study Completion: December 9, 2022
• Last Updated: May 7, 2024
• Results First Posted: September 9, 2021

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Within 6 months of official study closure at participating sites.
• Access Criteria: Available to the public

Locations

US (15)