ClinicalTrials.gov
ClinicalTrials.gov Menu

Vorinostat and Combination Chemotherapy With Rituximab in Treating Patients With HIV-Related Diffuse Large B-Cell Non-Hodgkin Lymphoma or Other Aggressive B-Cell Lymphomas

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: NCT01193842
Recruitment Status : Active, not recruiting
First Posted : September 2, 2010
Results First Posted : June 12, 2018
Last Update Posted : June 12, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions: AIDS-Related Plasmablastic Lymphoma
AIDS-Related Primary Effusion Lymphoma
CD20 Positive
HIV Infection
Plasmablastic Lymphoma
Primary Effusion Lymphoma
Recurrent Diffuse Large B-Cell Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Stage I Diffuse Large B-Cell Lymphoma
Stage I Grade 3 Follicular Lymphoma
Stage II Diffuse Large B-Cell Lymphoma
Stage II Grade 3 Contiguous Follicular Lymphoma
Stage II Grade 3 Non-Contiguous Follicular Lymphoma
Stage III Diffuse Large B-Cell Lymphoma
Stage III Grade 3 Follicular Lymphoma
Stage IV Diffuse Large B-Cell Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Interventions: Drug: Cyclophosphamide
Drug: Doxorubicin Hydrochloride
Drug: Etoposide
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Drug: Prednisone
Biological: Rituximab
Drug: Vincristine Sulfate
Drug: Vorinostat

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Phase I: VR-DA-EPOCH, Dose Level 1 Arm A (VR-DA-EPOCH) with Vorinostat at 300 mg once a day on days 1-5 of a cycle (Phase I Dose Level 1)
Phase I: VR-DA-EPOCH, Dose Level 2 Arm A (VR-DA-EPOCH) with Vorinostat at 400 mg once a day on days 1-5 of a cycle (Phase I Dose Level 2)
Phase I: VR-CHOP, Dose Level 1 Arm C (VR-CHOP) with Vorinostat at 300 mg once a day on days 1-5 of a cycle (Phase I Dose Level 1 for low risk participants). This arm was discontinued due to low accrual.
Phase II: VR-DA-EPOCH Arm A (VR-DA-EPOCH) at the recommended phase II dose of Vorinostat (300 mg once a day for days 1-5 of a cycle)
Phase II: DA-R-EPOCH Arm B (DA-R-EPOCH), which is the same treatment as Arm A, but without Vorinostat

Participant Flow for 5 periods

Period 1:   Phase I: VR-DA-EPOCH, Dose Level (DL) 1
    Phase I: VR-DA-EPOCH, Dose Level 1   Phase I: VR-DA-EPOCH, Dose Level 2   Phase I: VR-CHOP, Dose Level 1   Phase II: VR-DA-EPOCH   Phase II: DA-R-EPOCH
STARTED   3   0   0   0   0 
COMPLETED   3   0   0   0   0 
NOT COMPLETED   0   0   0   0   0 

Period 2:   Phase I: VR-DA-EPOCH, DL 2
    Phase I: VR-DA-EPOCH, Dose Level 1   Phase I: VR-DA-EPOCH, Dose Level 2   Phase I: VR-CHOP, Dose Level 1   Phase II: VR-DA-EPOCH   Phase II: DA-R-EPOCH
STARTED   0   7   0   0   0 
COMPLETED   0   6   0   0   0 
NOT COMPLETED   0   1   0   0   0 
Ineligible                0                1                0                0                0 

Period 3:   Phase I: VR-DA-EPOCH, DL 1 (De-escalate)
    Phase I: VR-DA-EPOCH, Dose Level 1   Phase I: VR-DA-EPOCH, Dose Level 2   Phase I: VR-CHOP, Dose Level 1   Phase II: VR-DA-EPOCH   Phase II: DA-R-EPOCH
STARTED   4   0   0   0   0 
COMPLETED   3   0   0   0   0 
NOT COMPLETED   1   0   0   0   0 
Ineligible                1                0                0                0                0 

Period 4:   Phase I: VR-CHOP, DL 1
    Phase I: VR-DA-EPOCH, Dose Level 1   Phase I: VR-DA-EPOCH, Dose Level 2   Phase I: VR-CHOP, Dose Level 1   Phase II: VR-DA-EPOCH   Phase II: DA-R-EPOCH
STARTED   0   0   2   0   0 
COMPLETED   0   0   1   0   0 
NOT COMPLETED   0   0   1   0   0 
Noncompliant (Cycle 1 not complete)                0                0                1                0                0 

Period 5:   Phase II: Randomized Groups
    Phase I: VR-DA-EPOCH, Dose Level 1   Phase I: VR-DA-EPOCH, Dose Level 2   Phase I: VR-CHOP, Dose Level 1   Phase II: VR-DA-EPOCH   Phase II: DA-R-EPOCH
STARTED   0   0   0   45   46 
COMPLETED   0   0   0   33   36 
NOT COMPLETED   0   0   0   12   10 
Death                0                0                0                1                1 
Adverse Event                0                0                0                5                3 
Withdrawal by Subject                0                0                0                1                2 
Ineligible                0                0                0                0                1 
Disease progression/relapse on treatment                0                0                0                5                3 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Eligible participants completing at least one cycle of treatment; 3 ineligible participants and 1 participant not completing one cycle of Phase I treatment were not included.

Reporting Groups
  Description
Phase I: VR-DA-EPOCH, Dose Level 1 Arm A (VR-DA-EPOCH) with Vorinostat at 300 mg once a day on days 1-5 of a cycle (Phase I Dose Level 1)
Phase I: VR-DA-EPOCH, Dose Level 2 Arm A (VR-DA-EPOCH) with Vorinostat at 400 mg once a day on days 1-5 of a cycle (Phase I Dose Level 2)
Phase I: VR-CHOP, Dose Level 1 Arm C (VR-CHOP) with Vorinostat at 300 mg once a day on days 1-5 of a cycle (Phase I Dose Level 1 for low risk participants). This arm was discontinued due to low accrual.
Phase II, V+DA-EPOCH Arm A (VR-DA-EPOCH) at the recommended phase II dose of Vorinostat (300 mg once a day for days 1-5 of a cycle)
Phase II, DA-R-EPOCH Arm B (DA-R-EPOCH), which is the same treatment as Arm A, but without Vorinostat
Total Total of all reporting groups

Baseline Measures
   Phase I: VR-DA-EPOCH, Dose Level 1   Phase I: VR-DA-EPOCH, Dose Level 2   Phase I: VR-CHOP, Dose Level 1   Phase II, V+DA-EPOCH   Phase II, DA-R-EPOCH   Total 
Overall Participants Analyzed 
[Units: Participants]
 6   6   1   45   45   103 
Age 
[Units: Years]
Mean (Standard Deviation)
 45.7  (12.4)   50.4  (10.1)   59.5  (0)   49.2  (10.1)   45  (9.2)   47.2  (9.8) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
           
Female      0   0.0%      1  16.7%      0   0.0%      6  13.3%      0   0.0%      7   6.8% 
Male      6 100.0%      5  83.3%      1 100.0%      39  86.7%      45 100.0%      96  93.2% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
           
Hispanic or Latino      1  16.7%      1  16.7%      0   0.0%      14  31.1%      13  28.9%      29  28.2% 
Not Hispanic or Latino      5  83.3%      5  83.3%      1 100.0%      29  64.4%      30  66.7%      70  68.0% 
Unknown or Not Reported      0   0.0%      0   0.0%      0   0.0%      2   4.4%      2   4.4%      4   3.9% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
           
American Indian or Alaska Native      0   0.0%      0   0.0%      0   0.0%      0   0.0%      1   2.2%      1   1.0% 
Asian      0   0.0%      0   0.0%      0   0.0%      2   4.4%      1   2.2%      3   2.9% 
Native Hawaiian or Other Pacific Islander      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Black or African American      2  33.3%      0   0.0%      0   0.0%      12  26.7%      8  17.8%      22  21.4% 
White      4  66.7%      6 100.0%      1 100.0%      23  51.1%      31  68.9%      65  63.1% 
More than one race      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Unknown or Not Reported      0   0.0%      0   0.0%      0   0.0%      8  17.8%      4   8.9%      12  11.7% 
Region of Enrollment 
[Units: Participants]
Count of Participants
           
United States   6   6   1   45   45   103 


  Outcome Measures

1.  Primary:   Percentage of Participants With Complete Response (CR) as Assessed by Response Evaluation Criteria in Solid Tumors (Phase II)   [ Time Frame: Up to 6 months ]

2.  Primary:   Percentage of Participant Experiencing Adverse Events (AEs) for Each Treatment Arm as Assessed by Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) (Phase II)   [ Time Frame: Up to 5 years ]

3.  Primary:   Recommended Phase II Dose of Vorinostat Determined According to Dose-limiting Toxicities Graded Using Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) (Phase I)   [ Time Frame: 21 days ]

4.  Secondary:   Change in CD8 Cell Counts (Phase I)   [ Time Frame: Baseline up to 12 months ]

5.  Secondary:   Changes in Absolute CD4 Cell Counts (Phase I)   [ Time Frame: Baseline up to 12 months ]

6.  Secondary:   Changes in Human Immunodeficiency Virus (HIV) Viral Load   [ Time Frame: Baseline up to 12 months ]

7.  Secondary:   Event-free Survival (EFS) (Phase II)   [ Time Frame: 1 year ]

8.  Secondary:   Overall Survival (OS) (Phase II)   [ Time Frame: 1 year ]

9.  Secondary:   Change in Plasma Associated Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) (Phase I)   [ Time Frame: Baseline up to 12 months ]

10.  Secondary:   Pharmacokinetic Clearance (Phase I)   [ Time Frame: 24-48, 48-72, and 72-96 hours after the start of the first chemotherapy infusion ]

11.  Secondary:   Tumor Response (Phase I)   [ Time Frame: Up to 2 years post treatment ]

12.  Secondary:   Changes in Epstein-Barr Virus (EBV) Viral Load   [ Time Frame: Baseline up to 12 months ]
Results not yet reported.   Anticipated Reporting Date:   06/2018  

13.  Secondary:   Changes in Human Herpes Virus (HHV)-8 Viral Load   [ Time Frame: Baseline up to 12 months ]
Results not yet reported.   Anticipated Reporting Date:   06/2018  


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Experimental Arm C (VR-CHOP) was discontinued early in phase I due to low accrual; only 2 participants received VR-CHOP.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: AMC Statistical Center
Organization: AIDS Malignancy Consortium
phone: 501-526-6712
e-mail: jylee@uams.edu



Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01193842     History of Changes
Other Study ID Numbers: NCI-2011-02508
NCI-2011-02508 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
AMC #75
CDR0000683379
AMC-075 ( Other Identifier: AIDS Malignancy Consortium )
AMC-075 ( Other Identifier: DCP )
AMC-075 ( Other Identifier: CTEP )
UM1CA121947 ( U.S. NIH Grant/Contract )
First Submitted: September 1, 2010
First Posted: September 2, 2010
Results First Submitted: February 23, 2018
Results First Posted: June 12, 2018
Last Update Posted: June 12, 2018