Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

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

Protocol: BMT-CTN1401

Full 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 (DC)/Myeloma Fusions

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).

Study Objective

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.

Are you eligible?

Inclusion 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-m

Exclusion 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-m

Multiple Myeloma