Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 52 of 882 for:    "Reticulum Cell Sarcoma"

Study of Intensive Consolidation and Stem Cell Mobilization Therapy Followed by Autologous Stem Cell Transplantation in High-risk Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

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: NCT01555541
Recruitment Status : Active, not recruiting
First Posted : March 15, 2012
Results First Posted : May 17, 2019
Last Update Posted : June 24, 2019
Sponsor:
Collaborators:
University of California, San Francisco
GlaxoSmithKline
Information provided by (Responsible Party):
C. Babis Andreadis, University of California, San Francisco

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Diffuse Large Cell Lymphoma Relapsed/Refractory
Interventions Drug: Ofatumumab
Drug: Etoposide
Drug: Cytarabine
Enrollment 19
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment
Hide Arm/Group Description

OVA Treatment:

Ofatumumab: 1000 mg IV days 0, 7, 14, 21

Etoposide: 10 mg/Kg IV over 24 hours daily, days 1-4

Cytarabine: 2000 mg/m2 IV twice daily, days 1-4

---------

After Day 42 assessment:

Autologous Transplantation:

Stem Cell Infusion on day 0

BCNU 15 mg/Kg, day -6

Etoposide 60 mg/Kg, day -4

Cyclophosphamide: 100 mg/Kg, day -2

Period Title: Salvage Response Assessment
Started 19
Completed 19
Not Completed 0
Period Title: OVA Treatment
Started 19
Completed 19
Not Completed 0
Period Title: Autologous Transplantation
Started 12
Completed 12
Not Completed 0
Arm/Group Title Treatment
Hide Arm/Group Description

OVA Treatment:

Ofatumumab: 1000 mg IV days 0, 7, 14, 21

Etoposide: 10 mg/Kg IV over 24 hours daily, days 1-4

Cytarabine: 2000 mg/m2 IV twice daily, days 1-4

---------

After Day 42 assessment:

Autologous Transplantation:

Stem Cell Infusion on day 0

BCNU 15 mg/Kg, day -6

Etoposide 60 mg/Kg, day -4

Cyclophosphamide: 100 mg/Kg, day -2

Overall Number of Baseline Participants 19
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
20-29
1
   5.3%
30-39
1
   5.3%
40-49
4
  21.1%
50-59
7
  36.8%
60-69
6
  31.6%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
Female
7
  36.8%
Male
12
  63.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
Hispanic or Latino
1
   5.3%
Not Hispanic or Latino
11
  57.9%
Unknown or Not Reported
7
  36.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
American Indian or Alaska Native
0
   0.0%
Asian
2
  10.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
9
  47.4%
More than one race
0
   0.0%
Unknown or Not Reported
8
  42.1%
1.Primary Outcome
Title Number of Patients Achieving Complete Response (CR) to the Treatment Upon Successful Stem Cell Mobilization
Hide Description

CR requires:

  1. Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.
  2. Post-treatment residual mass of any size is permitted as long as it is PET negative.
  3. Spleen and/or liver, if enlarged before therapy based on physical examination or CT scan, should not be palpable on physical examination and should be considered normal size by imaging studies, and nodules related to lymphoma should disappear.
  4. If bone marrow was involved by lymphoma before treatment, the infiltrate must have cleared on repeat bone marrow biopsy. The biopsy sample on which this determination is made must be adequate (with a goal of > 20 mm unilateral core). If the sample is indeterminate by morphology, it should be negative by immunohistochemistry. A sample that is negative by immunohistochemistry but that demonstrates a small population of clonal lymphocytes by flow cytometry will be considered a CR.
Time Frame Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment
Hide Arm/Group Description:

OVA Treatment:

Ofatumumab: 1000 mg IV days 0, 7, 14, 21

Etoposide: 10 mg/Kg IV over 24 hours daily, days 1-4

Cytarabine: 2000 mg/m2 IV twice daily, days 1-4

---------

After Day 42 assessment:

Autologous Transplantation:

Stem Cell Infusion on day 0

BCNU 15 mg/Kg, day -6

Etoposide 60 mg/Kg, day -4

Cyclophosphamide: 100 mg/Kg, day -2

Overall Number of Participants Analyzed 19
Measure Type: Count of Participants
Unit of Measure: Participants
10
  52.6%
2.Primary Outcome
Title Number of Patients Achieving Mobilization-adjusted Complete Response (maCR)
Hide Description Number of patients achieving complete response to the treatment upon successful stem cell mobilization, defined as at least 2 x10^6 cluster of differentiation 34 (CD34)+cells/Kg of actual body weight. Subjects who require use of plerixafor or an autologous bone marrow harvest are considered mobilization failures and will be treated as non- responders.
Time Frame Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment
Hide Arm/Group Description:

OVA Treatment:

Ofatumumab: 1000 mg IV days 0, 7, 14, 21

Etoposide: 10 mg/Kg IV over 24 hours daily, days 1-4

Cytarabine: 2000 mg/m2 IV twice daily, days 1-4

---------

After Day 42 assessment:

Autologous Transplantation:

Stem Cell Infusion on day 0

BCNU 15 mg/Kg, day -6

Etoposide 60 mg/Kg, day -4

Cyclophosphamide: 100 mg/Kg, day -2

Overall Number of Participants Analyzed 19
Measure Type: Count of Participants
Unit of Measure: Participants
10
  52.6%
3.Secondary Outcome
Title Time to Neutrophil Engraftment Following Autologous Stem Cell Transplantation (ASCT)
Hide Description Neutrophil engraftment is defined as the first day of 3 consecutive days with absolute neutrophil count of >500 cells/microliter (uL).
Time Frame Response evaluation will occur at day +90 after ASCT, and at 6, 12 and 24 months thereafter
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Time to Platelet Engraftment Following Autologous Stem Cell Transplantation (ASCT)
Hide Description Platelet engraftment is defined as the first of three consecutive measurements for which the platelet count was > 20,000/uL, and must be at least 24 hours following the last platelet transfusion.
Time Frame Response evaluation will occur at day +90 after ASCT, and at 6, 12 and 24 months thereafter
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Progression Free Survival
Hide Description Defined as time from day 0 until lymphoma progression, receipt of anti-lymphoma therapy (except for planned post-ASCT radiotherapy), or death as a result of any cause.
Time Frame Up to 48 months after ASCT
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Time to Progression
Hide Description Defined as time from study entry until documented lymphoma progression or receipt of anti-lymphoma therapy (except for planned post-ASCT radiotherapy) or death due to lymphoma.
Time Frame Up to 48 months after ASCT
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Event-Free Survival (EFS)
Hide Description Measured from day 0 to any treatment failure including disease progression, discontinuation of treatment for any reason, initiation of new therapy without documented progression, incidence of secondary Acute Myeloid Leukemia (AML) or Myelodysplastic syndromes (MDS), or death related to treatment.
Time Frame Up to 48 months after ASCT
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Overall Survival (OS)
Hide Description Defined as the time to death for any reason
Time Frame Up to 5 years after ASCT
Outcome Measure Data Not Reported
9.Secondary Outcome
Title CR/ Partial Response (PR) Proportion
Hide Description

CR: See above

PR requires:

  1. Post-treatment PET positive in at least one previously involved site
  2. ≥ 50% decrease in sum of product of the diameters (SPD) of up to 6 of largest dominant nodes/nodal masses
  3. No increase in size of other nodes, liver, spleen
  4. Splenic & hepatic nodules must regress ≥ 50% in their sum of the product of the greatest diameters (SPD) or, for single nodules, in the greatest transverse diameter
  5. Involvement of other organs assessable; no measurable disease present (except splenic or hepatic nodules)
  6. Bone marrow assessment irrelevant for PR determination if sample positive before treatment. Patients who achieve CR by above criteria, but with persistent morphologic bone marrow involvement will be considered partial responders. If bone marrow was involved before therapy and clinical CR was achieved, but with no bone marrow assessment after treatment, patients should be considered partial responders
  7. New sites of disease to be observed
Time Frame ~ Month 5
Hide Outcome Measure Data
Hide Analysis Population Description
patients who received OVA and then met criteria to proceed to auto and achieved a CR after auto
Arm/Group Title Single-arm Study
Hide Arm/Group Description:

Ofatumumab: 1000 mg IV days 0, 7, 14, 21

Etoposide: 10 mg/Kg IV over 24 hours daily, days 1-4

Cytarabine: 2000 mg/m2 IV twice daily, days 1-4

Overall Number of Participants Analyzed 19
Measure Type: Count of Participants
Unit of Measure: Participants
11
  57.9%
10.Secondary Outcome
Title Fluorodeoxyglucose-positron Emission Tomography (FDG-PET) Conversion Rate
Hide Description Number of patients who advance from PR to CR following OVA
Time Frame ~ Month 5
Hide Outcome Measure Data
Hide Analysis Population Description
patients with PR after salvage who converted to CR after OVA
Arm/Group Title Treatment
Hide Arm/Group Description:

OVA Treatment:

Ofatumumab: 1000 mg IV days 0, 7, 14, 21

Etoposide: 10 mg/Kg IV over 24 hours daily, days 1-4

Cytarabine: 2000 mg/m2 IV twice daily, days 1-4

---------

After Day 42 assessment:

Autologous Transplantation:

Stem Cell Infusion on day 0

BCNU 15 mg/Kg, day -6

Etoposide 60 mg/Kg, day -4

Cyclophosphamide: 100 mg/Kg, day -2

Overall Number of Participants Analyzed 6
Measure Type: Count of Participants
Unit of Measure: Participants
1
  16.7%
11.Secondary Outcome
Title Minimal Residual Disease (MRD)
Hide Description Minimal Residual Disease (MRD), based on the number of positive copies assessed by polymerase chain reaction (PCR)
Time Frame ~ Month 26
Outcome Measure Data Not Reported
12.Secondary Outcome
Title Unanticipated CTCAE Grade 3 or Higher Adverse Events
Hide Description NCI CTCAE v 4.0 grade 3 or higher adverse events in the first 24 months NOT anticipated to occur with autologous stem cell transplantation
Time Frame ~ Month 26
Outcome Measure Data Not Reported
Time Frame 5 years from study start
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment
Hide Arm/Group Description

OVA Treatment:

Ofatumumab: 1000 mg IV days 0, 7, 14, 21

Etoposide: 10 mg/Kg IV over 24 hours daily, days 1-4

Cytarabine: 2000 mg/m2 IV twice daily, days 1-4

---------

After Day 42 assessment:

Autologous Transplantation:

Stem Cell Infusion on day 0

BCNU 15 mg/Kg, day -6

Etoposide 60 mg/Kg, day -4

Cyclophosphamide: 100 mg/Kg, day -2

All-Cause Mortality
Treatment
Affected / at Risk (%)
Total   0/19 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Treatment
Affected / at Risk (%)
Total   5/19 (26.32%) 
Gastrointestinal disorders   
Anal Pain   1/19 (5.26%) 
Immune system disorders   
Allergic reaction   1/19 (5.26%) 
Infections and infestations   
Sepsis   1/19 (5.26%) 
Nervous system disorders   
Tremor   1/19 (5.26%) 
Respiratory, thoracic and mediastinal disorders   
Pneumonitis   1/19 (5.26%) 
Vascular disorders   
Vascular disorders - Other, specify   1/19 (5.26%) 
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Treatment
Affected / at Risk (%)
Total   9/19 (47.37%) 
Blood and lymphatic system disorders   
Febrile neutropenia   5/19 (26.32%) 
Anemia   3/19 (15.79%) 
Blood and lymphatic system disorders - Other, specify   1/19 (5.26%) 
Thrombotic thrombocytopenic purpura   1/19 (5.26%) 
Cardiac disorders   
Cardiac disorders - Other, specify   1/19 (5.26%) 
Gastrointestinal disorders   
Mucositis oral   4/19 (21.05%) 
Diarrhea   3/19 (15.79%) 
Nausea   3/19 (15.79%) 
Vomiting   2/19 (10.53%) 
Abdominal pain   1/19 (5.26%) 
Constipation   1/19 (5.26%) 
Enterocolitis   1/19 (5.26%) 
Retroperitoneal hemorrhage   1/19 (5.26%) 
General disorders   
Edema limbs   1/19 (5.26%) 
Infusion related reaction   1/19 (5.26%) 
Infections and infestations   
Infections and infestations - Other, specify   1/19 (5.26%) 
Lung infection   1/19 (5.26%) 
Sepsis   1/19 (5.26%) 
Investigations   
Platelet count decreased   9/19 (47.37%) 
Neutrophil count decreased   8/19 (42.11%) 
White blood cell decreased   4/19 (21.05%) 
Alanine aminotransferase increased   1/19 (5.26%) 
Aspartate aminotransferase increased   1/19 (5.26%) 
Metabolism and nutrition disorders   
Hyponatremia   1/19 (5.26%) 
Psychiatric disorders   
Insomnia   1/19 (5.26%) 
Respiratory, thoracic and mediastinal disorders   
Hypoxia   1/19 (5.26%) 
Skin and subcutaneous tissue disorders   
Rash maculo-papular   2/19 (10.53%) 
Vascular disorders   
Hypertension   1/19 (5.26%) 
Thromboembolic event   1/19 (5.26%) 
Indicates events were collected by systematic assessment
The study closed early due to low accrual. However, we are still following patients to collect survival information for the secondary outcome measures.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Charalambos Andreadis, MD, MSCE, Associate Professor of Clinical Medicine
Organization: University of California, San Francisco
Phone: 877-827-3222
EMail: clinicaltrials@ucsf.edu
Layout table for additonal information
Responsible Party: C. Babis Andreadis, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01555541     History of Changes
Other Study ID Numbers: 112525
First Submitted: March 9, 2012
First Posted: March 15, 2012
Results First Submitted: March 3, 2019
Results First Posted: May 17, 2019
Last Update Posted: June 24, 2019