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

NCT ID: NCT02728102

Last Updated: 2024-05-07

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

203 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-07-31

Study Completion Date

2022-12-09

Brief Summary

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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

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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.

Conditions

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Multiple Myeloma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Tumor Cell Collection

Intervention Type 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).

Autologous Stem Cell Transplant

Intervention Type 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.

Melphalan

Intervention Type 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.

Leukapheresis

Intervention Type PROCEDURE

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

Myeloma vaccine

Intervention Type 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.

GM-CSF

Intervention Type DRUG

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

Lenalidomide

Intervention Type 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.

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.

Group Type ACTIVE_COMPARATOR

Tumor Cell Collection

Intervention Type 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).

Autologous Stem Cell Transplant

Intervention Type 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.

Melphalan

Intervention Type 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.

GM-CSF

Intervention Type DRUG

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

Lenalidomide

Intervention Type 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.

Maintenance Lenalidomide

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

Group Type ACTIVE_COMPARATOR

Tumor Cell Collection

Intervention Type 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).

Autologous Stem Cell Transplant

Intervention Type 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.

Melphalan

Intervention Type 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.

Lenalidomide

Intervention Type 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.

Interventions

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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).

Intervention Type 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.

Intervention Type PROCEDURE

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.

Intervention Type DRUG

Leukapheresis

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

Intervention Type PROCEDURE

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.

Intervention Type BIOLOGICAL

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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Alkeran Dendritic cell fusion vaccine DC/MM fusion vaccine Granulocyte macrophage colony-stimulating factor Leukine Revlimid™

Eligibility Criteria

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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.


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.

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Blood and Marrow Transplant Clinical Trials Network

NETWORK

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

National Marrow Donor Program

OTHER

Sponsor Role collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mary Horowitz, MD

Role: STUDY_DIRECTOR

Center for International Blood and Marrow Transplant Research

Locations

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University of California, San Francisco

San Francisco, California, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

Site Status

Beth Israel Deaconess Medical Center/Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Mount Sinai Medical Center

New York, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

University Hospitals of Cleveland/Case Western

Cleveland, Ohio, United States

Site Status

Ohio State University/Arthur G. James Cancer Hospital

Columbus, Ohio, United States

Site Status

University of Texas/MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

University of Wisconsin Hospital & Clinics

Madison, Wisconsin, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 37463058 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

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http://bmtctn.net/

Blood and Marrow Transplant Clinical Trials Network

Other Identifiers

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U01HL069294

Identifier Type: NIH

Identifier Source: secondary_id

View Link

BMT CTN 1401

Identifier Type: -

Identifier Source: org_study_id

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