Vorinostat in Treating Patients With Relapsed or Refractory Advanced Hodgkin's Lymphoma

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00132028
• Collaborator: (none)
• Enrollment: 27
• Location: 1
• Arm: 1
• Duration (Months): 44
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This phase II trial is studying how well vorinostat works in treating patients with relapsed or refractory advanced Hodgkin's lymphoma. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Condition or Disease	Intervention/Treatment	Phase
Adult Favorable Prognosis Hodgkin Lymphoma; Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Adult Unfavorable Prognosis Hodgkin Lymphoma; Recurrent Adult Hodgkin Lymphoma	Drug: vorinostat; Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To evaluate the response probability (complete, complete unconfirmed, and partial) in patients with relapsed or refractory Hodgkin's lymphoma.

2. To estimate 1-year progression-free survival and overall survival in patients with relapsed or refractory Hodgkin's lymphoma treated with SAHA.

3. To assess the toxicity profile of SAHA in this patient population. IV. To perform gene expression profiling on tumor tissue before and after treatment in order to explore in a preliminary manner the association between response and specific gene expression results.

OUTLINE: This is a multicenter study.

Patients receive oral vorinostat twice daily on days 1-14. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 additional courses of therapy beyond CR.

After completion of study treatment, patients are followed every 6 months for 2 years and then annually for 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Suberoylanilide Hydroxamic Acid (NSC-701852) for Recurrent or Primary Refractory Hodgkin's Lymphoma
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: May 1, 2009
• Actual Study Completion Date: May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (vorinostat) Patients receive oral vorinostat twice daily on days 1-14. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 additional courses of therapy beyond CR.	Drug: vorinostat; Given orally; Other Names: L-001079038 SAHA suberoylanilide hydroxamic acid Zolinza ; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Assess Number of Patients Who Achieve Confirmed and Unconfirmed Complete Response (CR) or Partial Response (PR) [after every 3 cycles on treatment]

   Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM. Partial Response(PR) is a 50% decrease in the SPD for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes.

Secondary Outcome Measures

1. Progression-Free Survival [after every 3 cycles on treatment, then every 6 months for 2 years, then annually for a total of 5 years.]

   Measured from date of registration to date of first observation of progression or death, or last contact date. Progression is defined as a 50% increase in sum of products of greatest diameters (SPD) of target measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline; appearance of a new lesion/site; unequivocal progression of non-measurable disease in the opinion of the treating physician; death due to disease without prior documentation of progression.

2. Overall Survival [after every 3 cycles on treatment, then every 6 months for 2 years, then annually for a total of 5 years.]

   Measured from date of registration to death, or last contact date

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed relapsed/refractory Hodgkin's lymphoma of any subtype; patients with lymphocyte predominant Hodgkin's disease (LPHD) are also eligible; clear evidence of disease progression or lack of response after the most recent therapy, including local radiation is required

• Patients must be willing to submit specimens for correlative studies

• All patients must have bidimensionally measurable disease documented within 28 days prior to registration; patients with non-measurable disease in addition to measurable disease must have all non-measurable disease assessed within 42 days prior to registration

• Patients must have unilateral bone marrow aspirate and biopsy performed within 42 days prior to registration

• Patients may have had up to five prior chemotherapy regimens

• Patients must have completed chemotherapy at least 28 days prior to registration and all toxicities must have resolved (in the opinion of the treating investigator); if last regimen included nitrosoureas or mitomycin then 42 days must have elapsed since completion of treatment; patients must not have taken valproic acid, or another histone deacetylase inhibitor, for at least 14 days prior to registration

• Patients must have completed all radiotherapy at least 14 days prior to registration and all toxicities must have resolved (in the opinion of the treating investigator)

• Patients who relapse after autologous stem cell transplant may be enrolled if they are at least three months after transplant, and after allogeneic transplant if they are at least one year posttransplant; patients should have no active related infections (i.e., fungal or viral); in the case of allogeneic transplant relapse, there should be no active acute graft versus host disease (GvHD) of any grade, and no chronic graft versus host disease other than mild skin, oral, or ocular GvHD not requiring systemic immunosuppression

• Patients must have a Zubrod performance status of 0-2

• Patients must have a CT scan of the chest/abdomen and pelvis performed within 28 days prior to registration

• Patients must not have clinical evidence of central nervous system involvement by lymphoma; any laboratory or radiographic tests performed to assess CNS involvement must be negative within 42 days of registration

• Serum LDH must be measured within 28 days prior to registration

• Absolute neutrophil count >- 1,000/mcL

• Platelet count >= 100,000/mcL

• SGOT/SGPT < 2.5 x the institutional upper limit of normal

• Serum creatinine < 2 x the institutional upper limit of normal

• Patients with a history of allergic reactions attributed to compounds of similar chemical or biological composition to SAHA are ineligible

• Patients must not have plans to receive concurrent hormonal, biological or radiation therapy; patients with potentially curative options such as salvage therapy with chemotherapy or hematopoietic stem cell transplant (HSCT) are not eligible

• Patients with a history of prior myocardial infarction, unstable angina, or stroke within 6 months are ineligible

• Patients known to be HIV-positive and receiving combination antiretroviral therapy are ineligible; in addition, HIV-positive patients not receiving combination antiretroviral therapy are also ineligible

• No prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer for which the patient has been disease-free for five years

• Pregnant or nursing women may not participate; women or men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method

• Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Southwest Oncology Group (SWOG) Research Base	San Antonio	Texas	United States	78245

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Mark Kirschbaum, Southwest Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00132028
• Other Study ID Numbers: NCI-2012-03071; NCI-2012-03071; U10CA032102; S0517; S0517
• First Posted: Aug 19, 2005
• Last Update Posted: May 23, 2014
• Last Verified: Jan 1, 2013

• Additional relevant MeSH terms: Lymphoma; Hodgkin Disease; Vorinostat

Study Results

Participant Flow

Arm/Group Title	SAHA (Vorinostat)
Arm/Group Description	Patients receive vorinostat 400 mg/day on days 1-14 of every 21-day cycle. Patients continue treatment until progression.
Period Title: Overall Study
STARTED	27
Eligible	25
Eligible and Began Protocol Therapy	25
COMPLETED	0
NOT COMPLETED	27

Baseline Characteristics

Arm/Group Title	SAHA (Vorinostat)
Arm/Group Description	Patients receive vorinostat 400 mg/day on days 1-14 of every 21-day cycle. Patients continue treatment until progression.
Overall Participants	25
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	41.6
Sex: Female, Male (Count of Participants)
Female	11 44%
Male	14 56%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 12%
Not Hispanic or Latino	17 68%
Unknown or Not Reported	5 20%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 12%
White	20 80%
More than one race	0 0%
Unknown or Not Reported	1 4%

Outcome Measures

1. Primary Outcome

Title	Assess Number of Patients Who Achieve Confirmed and Unconfirmed Complete Response (CR) or Partial Response (PR)
Description	Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM. Partial Response(PR) is a 50% decrease in the SPD for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes.
Time Frame	after every 3 cycles on treatment

Outcome Measure Data

Analysis Population Description

All patients who started treatment were included in assessing response estimates.

Arm/Group Title	SAHA (Vorinostat)
Arm/Group Description	Patients receive vorinostat 400 mg/day on days 1-14 of every 21-day cycle. Patients continue treatment until progression.
Measure Participants	25
Complete Response (CR)	0 0%
Partial Response (PR)	1 4%
Unconfirmed Complete Response (UCR)	0 0%
Unconfirmed Partial Response (UPR)	0 0%
No Response	24 96%

2. Secondary Outcome

Title	Progression-Free Survival
Description	Measured from date of registration to date of first observation of progression or death, or last contact date. Progression is defined as a 50% increase in sum of products of greatest diameters (SPD) of target measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline; appearance of a new lesion/site; unequivocal progression of non-measurable disease in the opinion of the treating physician; death due to disease without prior documentation of progression.
Time Frame	after every 3 cycles on treatment, then every 6 months for 2 years, then annually for a total of 5 years.

Outcome Measure Data

Analysis Population Description

All eligible patients who started treatment were included in assessing progression-free survival.

Arm/Group Title	SAHA (Vorinostat)
Arm/Group Description	Patients receive vorinostat 400 mg/day on days 1-14 of every 21-day cycle. Patients continue treatment until progression.
Measure Participants	25
Median (95% Confidence Interval) [months]	4.8

3. Secondary Outcome

Title	Overall Survival
Description	Measured from date of registration to death, or last contact date
Time Frame	after every 3 cycles on treatment, then every 6 months for 2 years, then annually for a total of 5 years.

Outcome Measure Data

Analysis Population Description

All eligible patients who started treatment were included in assessing overall survival.

Arm/Group Title	SAHA (Vorinostat)
Arm/Group Description	Patients receive vorinostat 400 mg/day on days 1-14 of every 21-day cycle. Patients continue treatment until progression.
Measure Participants	25
Median (95% Confidence Interval) [months]	15.7

Adverse Events

Time Frame	After every 21-day cycle while on protocol treatment
Arm/Group Title	SAHA (Vorinostat)
Arm/Group Description
All Cause Mortality
	SAHA (Vorinostat)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	SAHA (Vorinostat)
	Affected / at Risk (%)	# Events
Total	5/25 (20%)
Blood and lymphatic system disorders
Hemoglobin	2/25 (8%)
Gastrointestinal disorders
Constipation	1/25 (4%)
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils - Bladder (urinary)	1/25 (4%)
Investigations
Creatinine	1/25 (4%)
INR (International Normalized Ratio of prothrombin time)	1/25 (4%)
Platelets	2/25 (8%)
Metabolism and nutrition disorders
Anorexia	1/25 (4%)
Glucose, serum-high (hyperglycemia)	1/25 (4%)
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy) - Whole body/generalized	1/25 (4%)
Renal and urinary disorders
Urinary retention (including neurogenic bladder)	1/25 (4%)
Vascular disorders
Hypotension	1/25 (4%)
Other (Not Including Serious) Adverse Events
	SAHA (Vorinostat)
	Affected / at Risk (%)	# Events
Total	25/25 (100%)
Blood and lymphatic system disorders
Hemoglobin	20/25 (80%)
Gastrointestinal disorders
Constipation	3/25 (12%)
Diarrhea	11/25 (44%)
Dry mouth/salivary gland (xerostomia)	3/25 (12%)
Nausea	16/25 (64%)
Pain - Stomach	2/25 (8%)
Vomiting	8/25 (32%)
General disorders
Fatigue (asthenia, lethargy, malaise)	16/25 (64%)
Fever (in the absence of neutropenia, where neutropenia is defined as ANC lt1.0 x 10e9/L)	4/25 (16%)
Flu-like syndrome	3/25 (12%)
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils - Lung (pneumonia)	2/25 (8%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Urinary tract NOS	2/25 (8%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	4/25 (16%)
AST, SGOT (serum glutamic oxaloacetic transaminase)	7/25 (28%)
Alkaline phosphatase	7/25 (28%)
Bilirubin (hyperbilirubinemia)	2/25 (8%)
Creatinine	6/25 (24%)
Leukocytes (total WBC)	7/25 (28%)
Lymphopenia	11/25 (44%)
Neutrophils/granulocytes (ANC/AGC)	4/25 (16%)
Platelets	11/25 (44%)
Weight loss	5/25 (20%)
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	4/25 (16%)
Anorexia	10/25 (40%)
Calcium, serum-low (hypocalcemia)	3/25 (12%)
Dehydration	3/25 (12%)
Glucose, serum-high (hyperglycemia)	2/25 (8%)
Potassium, serum-low (hypokalemia)	3/25 (12%)
Sodium, serum-low (hyponatremia)	4/25 (16%)
Uric acid, serum-high (hyperuricemia)	3/25 (12%)
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy) - Whole body/generalized	3/25 (12%)
Pain - Muscle	2/25 (8%)
Nervous system disorders
Dizziness	2/25 (8%)
Neuropathy: sensory	3/25 (12%)
Pain - Head/headache	5/25 (20%)
Taste alteration (dysgeusia)	2/25 (8%)
Renal and urinary disorders
Proteinuria	3/25 (12%)
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	4/25 (16%)
Skin and subcutaneous tissue disorders
Dry skin	2/25 (8%)
Hair loss/Alopecia (scalp or body)	4/25 (16%)
Rash/desquamation	2/25 (8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.