Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Tadalafil and Lenalidomide Maintenance With or Without Activated Marrow Infiltrating Lymphocytes (MILs) in High Risk Myeloma

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: NCT01858558
Recruitment Status : Completed
First Posted : May 21, 2013
Results First Posted : June 29, 2020
Last Update Posted : June 29, 2020
Sponsor:
Collaborator:
The Leukemia and Lymphoma Society
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Myeloma
Interventions Biological: aMIL
Drug: No aMIL
Enrollment 102
Recruitment Details Participants were enrolled at four sites: Johns Hopkins University, Moffitt Cancer Center, Mayo Clinic (Jacksonville) and the Blood and Marrow Transplant Group of Georgia (Northside).
Pre-assignment Details Of the 102 patients randomized, one was randomized to the control group who was lost to follow-up prior to start; did not have aMILs harvested, and was not transplanted. This patient is therefore not included in this report.
Arm/Group Title aMIL Arm No aMIL
Hide Arm/Group Description

Patients receive activated Marrow Infiltrating Lymphocytes (aMIL)

aMIL: On day 0, patients will receive auto transplant followed by Tadalafil and aMIL. At day 60, patients will receive Lenalidomide.

Patients do not receive activated Marrow Infiltrating Lymphocytes (aMIL)

No aMIL: On day 0, patients will receive auto transplant followed by Tadalafil. At day 60, patients will receive Lenalidomide.

Period Title: Overall Study
Started 70 31
Completed 61 29
Not Completed 9 2
Reason Not Completed
Death             1             1
Lost to Follow-up             1             0
Disease progression             3             1
Product contamination             2             0
Failed expansion of cell product             2             0
Arm/Group Title aMIL Arm No aMIL Total
Hide Arm/Group Description

Patients receive activated Marrow Infiltrating Lymphocytes (aMIL)

aMIL: On day 0, patients will receive auto transplant followed by Tadalafil and aMIL. At day 60, patients will receive Lenalidomide.

Patients do not receive activated Marrow Infiltrating Lymphocytes (aMIL)

No aMIL: On day 0, patients will receive auto transplant followed by Tadalafil. At day 60, patients will receive Lenalidomide.

Total of all reporting groups
Overall Number of Baseline Participants 70 31 101
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 70 participants 31 participants 101 participants
62.5
(35.0 to 74.8)
59.0
(37.1 to 75.9)
61.7
(35.0 to 75.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 70 participants 31 participants 101 participants
Female
36
  51.4%
15
  48.4%
51
  50.5%
Male
34
  48.6%
16
  51.6%
50
  49.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 70 participants 31 participants 101 participants
Asian
1
   1.4%
1
   3.2%
2
   2.0%
Black
14
  20.0%
8
  25.8%
22
  21.8%
Other
2
   2.9%
1
   3.2%
3
   3.0%
White
53
  75.7%
21
  67.7%
74
  73.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 70 participants 31 participants 101 participants
70 31 101
Disease Status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 70 participants 31 participants 101 participants
Newly Diagnosed
60
  85.7%
26
  83.9%
86
  85.1%
Relapsed
10
  14.3%
5
  16.1%
15
  14.9%
Myeloma Prognostic Risk Signature (MYPRS) Risk Category   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 70 participants 31 participants 101 participants
High Risk
12
  17.1%
4
  12.9%
16
  15.8%
Low Risk
25
  35.7%
15
  48.4%
40
  39.6%
N/A
8
  11.4%
2
   6.5%
10
   9.9%
Indeterminate
25
  35.7%
10
  32.3%
35
  34.7%
[1]
Measure Description: The Myeloma Prognostic Risk Signature (MyPRS®) (Signal Genetics™) is used to estimate the underlying activity of disease progression in patients diagnosed with active multiple myeloma.
70-gene expression Prognostic Risk Score (GEP-70)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 70 participants 31 participants 101 participants
Not High Risk
58
  82.9%
27
  87.1%
85
  84.2%
High Risk
12
  17.1%
4
  12.9%
16
  15.8%
[1]
Measure Description: The 70-gene Prognostic Risk Score (GEP-70) quantifies the expression of 70 genes commonly altered in multiple myeloma. Primarily prognostic, GEP-70 assesses risk of disease relapse and survival outcomes and is the randomization stratification of the MYPRS multiple myeloma specific gene expression profile risk categories.
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 70 participants 31 participants 101 participants
0
27
  38.6%
7
  22.6%
34
  33.7%
1 or 2
34
  48.6%
21
  67.7%
55
  54.5%
Missing
9
  12.9%
3
   9.7%
12
  11.9%
[1]
Measure Description:

ECOG Scoring System

0= Fully active, able to carry on all pre-disease performance without restriction

  1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
  2. Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50% of waking hours
  3. Capable of only limited self care, confined to bed or chair more than 50% of waking hours
  4. Completely disabled. Cannot carry on any self care. Totally confined to bed or chair
  5. Dead
International Staging System (ISS) Multiple Myeloma Classification   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 70 participants 31 participants 101 participants
Stage I
20
  28.6%
10
  32.3%
30
  29.7%
Stage II
19
  27.1%
7
  22.6%
26
  25.7%
Stage III
17
  24.3%
8
  25.8%
25
  24.8%
missing
14
  20.0%
6
  19.4%
20
  19.8%
[1]
Measure Description:

Prognosticates the severity of multiple myeloma and patient survival based on routinely obtained lab values.

Stage I= Serum β2 microglobulin < 3.5 mg/l; serum albumin ≥ 3.5 g/dl; standard-risk chromosomal abnormalities (CA) and normal lactate dehydrogenase (LDH) Stage II= not stage I or Stage III Stage III= Serum β2 microglobulin ≥ 5.5 mg/L and either high-risk CA by florescent in situ hybridization (FISH) or high LDH

Salmon Stage multiple myeloma classification   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 70 participants 31 participants 101 participants
IA-IB
9
  12.9%
0
   0.0%
9
   8.9%
IIA-IIB
14
  20.0%
7
  22.6%
21
  20.8%
IIIA-IIIB
35
  50.0%
21
  67.7%
56
  55.4%
missing
12
  17.1%
3
   9.7%
15
  14.9%
[1]
Measure Description:

demonstrates the correlation between the amount of myeloma and the damage it has caused based on number of bone lesions, anemia, serum calcium levels, and serum and urine light chain levels, and can be measured as myeloma cell mass (myeloma cells in billions/m2)* .

Stage I= low cell mass (600 billion) Stage II= intermediate cell mass (600-1200 billion) Stage III= high cell mass (>1200 billion)

Subcategory:

A = normal renal function. B= abnormal renal function

Number of Prior Multiple Myeloma Treatments  
Median (Inter-Quartile Range)
Unit of measure:  Prior treatments
Number Analyzed 70 participants 31 participants 101 participants
1
(1 to 6)
2
(1 to 5)
1
(1 to 6)
Time to Diagnosis  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 70 participants 31 participants 101 participants
0.53
(0.07 to 8.15)
0.76
(0.38 to 4.80)
0.55
(0.07 to 8.15)
Time to stem cell transplant (SCT)  
Median (Inter-Quartile Range)
Unit of measure:  Days
Number Analyzed 70 participants 31 participants 101 participants
63.0
(35.0 to 403.0)
56.0
(33.0 to 246.0)
60.0
(33.0 to 403.0)
1.Primary Outcome
Title Feasibility of MILs as Assessed by the Ability to Harvest, Expand, and Infuse the MILs Product
Hide Description Feasibility is defined as the ability to harvest, expand, and infuse the MILs product within 120 days. After treating 60 patients with MILs, we will declare MILs not feasible if we can only harvest, expand, and deliver MILs to 40 or fewer patients.
Time Frame 120 days
Hide Outcome Measure Data
Hide Analysis Population Description
71 patients were evaluable in the feasibility set: 70 randomized to the aMILs Arm, plus one patient who was not randomized due to harvest failure.
Arm/Group Title aMIL Arm
Hide Arm/Group Description:

Patients receive activated Marrow Infiltrating Lymphocytes (aMIL)

aMIL: On day 0, patients will receive auto transplant followed by Tadalafil and aMIL. At day 60, patients will receive Lenalidomide.

Overall Number of Participants Analyzed 71
Measure Type: Count of Participants
Unit of Measure: Participants
Total number who received aMILS
71
 100.0%
Feasible
46
  64.8%
Reason not feasible- failed harvest
1
   1.4%
Reason not feasible- disease progression
4
   5.6%
Reason not feasible- death
1
   1.4%
Reason not feasible- lost to follow-up
1
   1.4%
Reason not feasible- failed expansion
2
   2.8%
Reason not feasible- cell product contamination
2
   2.8%
Reason not feasible- greater than 120 days
14
  19.7%
2.Secondary Outcome
Title Toxicity as Determined by Total Number of Grade 3 or Higher Adverse Events
Hide Description Total number of adverse events grade 3 or higher that occur from MILs harvest through 60 days after transplant.
Time Frame 60 days from aMILs harvest until day 60 after transplant
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title aMIL Arm No aMIL
Hide Arm/Group Description:

Patients receive activated Marrow Infiltrating Lymphocytes (aMIL)

aMIL: On day 0, patients will receive auto transplant followed by Tadalafil and aMIL. At day 60, patients will receive Lenalidomide.

Patients do not receive activated Marrow Infiltrating Lymphocytes (aMIL)

No aMIL: On day 0, patients will receive auto transplant followed by Tadalafil. At day 60, patients will receive Lenalidomide.

Overall Number of Participants Analyzed 70 31
Measure Type: Number
Unit of Measure: adverse events
129 65
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS assessed by number of participants alive at the end of follow up period.
Time Frame 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
This is an analysis by intention-to-treat and only considers transplanted patients randomized to the aMILs arm.
Arm/Group Title aMIL Arm
Hide Arm/Group Description:

Patients receive activated Marrow Infiltrating Lymphocytes (aMIL)

aMIL: On day 0, patients will receive auto transplant followed by Tadalafil and aMIL. At day 60, patients will receive Lenalidomide.

Overall Number of Participants Analyzed 70
Measure Type: Count of Participants
Unit of Measure: Participants
55
  78.6%
4.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description Median PFS time equals the time of randomization (in months) until disease progression, death from any cause, or protocol deviation due to lenalidomide dosing (above 10mg), whichever occurs first.
Time Frame 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
This is an analysis by intention-to-treat and only considers transplanted patients randomized to the aMILs arm.
Arm/Group Title aMIL Arm
Hide Arm/Group Description:

Patients receive activated Marrow Infiltrating Lymphocytes (aMIL)

aMIL: On day 0, patients will receive auto transplant followed by Tadalafil and aMIL. At day 60, patients will receive Lenalidomide.

Overall Number of Participants Analyzed 70
Median (Inter-Quartile Range)
Unit of Measure: months
21.82
(18.53 to 41.82)
Time Frame 60 Days from aMILs harvest until Day 60 after transplant
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title aMIL Arm No aMIL
Hide Arm/Group Description

Patients receive activated Marrow Infiltrating Lymphocytes (aMIL)

aMIL: On day 0, patients will receive auto transplant followed by Tadalafil and aMIL. At day 60, patients will receive Lenalidomide.

Patients do not receive activated Marrow Infiltrating Lymphocytes (aMIL)

No aMIL: On day 0, patients will receive auto transplant followed by Tadalafil. At day 60, patients will receive Lenalidomide.

All-Cause Mortality
aMIL Arm No aMIL
Affected / at Risk (%) Affected / at Risk (%)
Total   1/70 (1.43%)      1/31 (3.23%)    
Hide Serious Adverse Events
aMIL Arm No aMIL
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   64/70 (91.43%)      29/31 (93.55%)    
Blood and lymphatic system disorders     
Febrile neutropenia * 1 [1]  36/70 (51.43%)  45 18/31 (58.06%)  22
Anemia * 1 [2]  3/70 (4.29%)  3 0/31 (0.00%)  0
Pancytopenia * 1 [2]  2/70 (2.86%)  2 0/31 (0.00%)  0
lymphocyte count decreased * 1 [2]  1/70 (1.43%)  1 1/31 (3.23%)  2
neutrophil count decreased * 1 [2]  7/70 (10.00%)  10 3/31 (9.68%)  4
platelet count decreased * 1 [2]  3/70 (4.29%)  7 4/31 (12.90%)  4
white blood cell decreased * 1  2/70 (2.86%)  4 1/31 (3.23%)  1
Cardiac disorders     
Atrial Fibrillation * 1 [2]  1/70 (1.43%)  1 1/31 (3.23%)  2
ventricular arrhythmia * 1 [2]  1/70 (1.43%)  1 0/31 (0.00%)  0
Gastrointestinal disorders     
Colitis * 1 [2]  1/70 (1.43%)  1 0/31 (0.00%)  0
Diarrhea * 1 [2]  8/70 (11.43%)  8 1/31 (3.23%)  1
Esophagitis * 1 [2]  1/70 (1.43%)  1 0/31 (0.00%)  0
Gastric ulcer * 1 [2]  0/70 (0.00%)  0 1/31 (3.23%)  1
nausea * 1 [2]  1/70 (1.43%)  2 2/31 (6.45%)  3
vomiting * 1 [2]  0/70 (0.00%)  0 2/31 (6.45%)  2
General disorders     
Fatigue * 1 [2]  2/70 (2.86%)  2 0/31 (0.00%)  0
fever * 1 [2]  4/70 (5.71%)  4 1/31 (3.23%)  1
Infections and infestations     
Enterocolitis infection * 1 [2]  0/70 (0.00%)  0 1/31 (3.23%)  1
bacteremia * 1 [2]  3/70 (4.29%)  3 2/31 (6.45%)  2
lung infection * 1 [2]  2/70 (2.86%)  2 2/31 (6.45%)  2
mucosal infection * 1 [2]  11/70 (15.71%)  11 5/31 (16.13%)  5
Scrotal Infection * 1 [2]  1/70 (1.43%)  1 0/31 (0.00%)  0
Sepsis * 1 [2]  2/70 (2.86%)  2 0/31 (0.00%)  0
upper respiratory infection * 1 [2]  1/70 (1.43%)  1 1/31 (3.23%)  1
Injury, poisoning and procedural complications     
Device related infection * 1 [2]  0/70 (0.00%)  0 1/31 (3.23%)  1
Metabolism and nutrition disorders     
dehydration * 1 [2]  1/70 (1.43%)  1 0/31 (0.00%)  0
hypocalcemia * 1 [2]  1/70 (1.43%)  1 0/31 (0.00%)  0
hypophosphatemia * 1 [2]  4/70 (5.71%)  5 0/31 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back Pain * 1 [2]  1/70 (1.43%)  1 1/31 (3.23%)  2
Bone Pain * 1 [2]  3/70 (4.29%)  3 0/31 (0.00%)  0
Nervous system disorders     
headache * 1 [2]  1/70 (1.43%)  1 0/31 (0.00%)  0
Stroke * 1 [2]  0/70 (0.00%)  0 1/31 (3.23%)  1
syncope * 1 [2]  2/70 (2.86%)  2 2/31 (6.45%)  2
Renal and urinary disorders     
Acute Kidney Injury * 1 [2]  0/70 (0.00%)  0 1/31 (3.23%)  1
Kidney infection * 1 [2]  0/70 (0.00%)  0 1/31 (3.23%)  1
renal calculi * 1 [2]  0/70 (0.00%)  0 1/31 (3.23%)  1
Respiratory, thoracic and mediastinal disorders     
hypoxia * 1 [2]  1/70 (1.43%)  1 0/31 (0.00%)  0
Vascular disorders     
hypotension * 1 [2]  1/70 (1.43%)  1 1/31 (3.23%)  1
thromboembolic event * 1 [2]  1/70 (1.43%)  1 1/31 (3.23%)  1
1
Term from vocabulary, CTCAE (4.0)
*
Indicates events were collected by non-systematic assessment
[1]
Grade 3 or higher Adverse Events (AEs) from aMILs harvest to 60 days following autologous stem cell transplant (ASCT)
[2]
Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
aMIL Arm No aMIL
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/70 (15.71%)      0/31 (0.00%)    
General disorders     
infusion related reaction * 1 [1]  8/63 (12.70%)  8 0/31 (0.00%)  0
Product Issues     
manufacture failure * 1  2/70 (2.86%)  2 0/31 (0.00%)  0
product contamination * 1  1/70 (1.43%)  1 0/31 (0.00%)  0
1
Term from vocabulary, CTCAE (4.0)
*
Indicates events were collected by non-systematic assessment
[1]
63 participants in the aMILs Arm had infusions, of those, 8 had record of infusion reaction.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Philip Imus, MD
Organization: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Phone: 410-955-8873
EMail: pimus1@jhmi.edu
Layout table for additonal information
Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT01858558    
Other Study ID Numbers: J1343
NA_00084466 ( Other Identifier: JHMIRB )
First Submitted: May 14, 2013
First Posted: May 21, 2013
Results First Submitted: June 11, 2020
Results First Posted: June 29, 2020
Last Update Posted: June 29, 2020