FR901228 in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
Study Details
Study Description
Brief Summary
FR901228 may stop the growth of cancer cells by blocking some of the enzymes needed for cell to grow and by blocking blood flow to the cancer. This phase II trial is studying how well FR901228 works in treating patients with relapsed or refractory non-Hodgkin's lymphoma.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 2 |
Detailed Description
OBJECTIVES:
-
Determine the response rate (complete and partial) to FR901228 in patients with relapsed or refractory mantle cell or diffuse large cell non-Hodgkin's lymphoma.
-
Evaluate the safety and feasibility of FR901228, in terms of the incidence of toxicity and maximum grade observed and courses delayed or dose reductions, in these patients.
-
Determine 2-year progression-free and overall survival.
OUTLINE: Patients receive FR901228 IV over 4 hours on days 1, 8, and 15.
Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3-6 months for up to 5 years.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Arm I Patients receive FR901228 IV over 4 hours on days 1, 8, and 15. |
Drug: romidepsin
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Overall Objective Response Rate (Complete Response [CR] and Partial Response [PR]) After 6 Courses of Treatment [24 weeks (6 courses of 4 week cycles)]
International Working Group response for non- Hodgkin's lymphoma: Complete Response (CR) - disappearance all detectable clinical/radiographic evidence of disease and disappearance of all disease-related symptoms (present before therapy) and normalization of those biochemical abnormalities; Partial Response (PR) - ≥50% decrease in sum products of greatest diameters (SPD) of 6 largest dominant nodes or nodal masses, selected by clearly measurable in at least two perpendicular dimensions, from disparate regions of body and no decrease in size of other nodes, liver, or spleen.
Secondary Outcome Measures
- Median Progression Free-survival (PFS) [2 Years]
Time to disease progression is defined as the time from registration to documentation of disease progression.
- Median Overall Survival [5 Years]
Survival time is defined as the time from registration to death due to any cause, measured in months. The distribution of survival time estimated using the method of Kaplan-Meier.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically confirmed aggressive B-cell non-Hodgkin's lymphoma of 1 of the following subtypes:
-
Mantle cell lymphoma
-
Diffuse large cell lymphoma
-
(Ineligible for or unwilling to undergo stem cell transplantation)
-
Relapsed or refractory disease:
-
Any number of prior therapies allowed for relapsed disease, including peripheral blood stem cell or bone marrow transplantation
-
No more than 2 prior regimens, excluding monotherapy with monoclonal antibody or radiotherapy, for refractory disease
-
Measurable disease, defined as >= 1 lesion >= 1.5 cm in the longest diameter
-
No transformed lymphoma, defined as the transformation of a low-grade lymphoma, including follicular lymphoma or small lymphocytic lymphoma, to a high-grade lymphoma (e.g., diffuse large cell lymphoma)
-
ECOG performance status 0-2
-
Absolute neutrophil count >= 1,000/mm3 OR >= 500/mm3 if extensive bone marrow involvement (> 50%) or hypersplenism with palpable splenomegaly
-
Platelet count >= 75,000/mm3 OR >= 50,000/mm3 if extensive bone marrow involvement (> 50%) or hypersplenism with palpable splenomegaly
-
Bilirubin normal
-
Alkaline phosphatase =< 2 times upper limit of normal (ULN)
-
AST =< 2 times ULN
-
Not pregnant or nursing
-
Negative pregnancy test
-
Fertile patients must use effective contraception
-
No significant cardiac disease, including New York Heart Association class III-IV congestive heart failure
-
No history of serious ventricular arrhythmia
-
QTc < 500 msec
-
No evidence of cardiac hypertrophy on ECG
-
No known HIV positivity
-
No other uncontrolled serious medical condition or active infection (e.g., chronic obstructive pulmonary disease, diabetes)
-
Recovered from prior therapy
-
No prior doxorubicin hydrochloride >= 450 mg/m2 or mitoxantrone >= 112 mg/m2 (Patients who received both mitoxantrone and doxorubicin hydrochloride should have a "doxorubicin equivalent dose" < 450 mg/m^2
-
No prior therapy with a histone deacetylase inhibitor
-
No concurrent dexamethasone or prednisone except for refractory nausea/vomiting
-
No concurrent drugs associated with QTc prolongation (e.g., dolasetron mesylate)
-
Concurrent hydrochlorothiazide, furosemide, or other diuretics allowed provided patient is receiving potassium chloride supplementation (No supplementation needed if switched to a potassium-conserving diuretic)
-
No CNS lymphoma
-
Creatinine normal
-
Cardiac function >= 50% by MUGA
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | M D Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Jorge Romaguera, M.D. Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCI-2009-00240
- NCI-2009-00240
- 2005-0579
- CDR0000486326
- 2005-0579
- 7869
- P30CA016672
- N01CM62202
Study Results
Participant Flow
Recruitment Details | Recruitment Period: September 20, 2006 to May 08, 2009. All recruitment done at UT MD Anderson Cancer Center. |
---|---|
Pre-assignment Detail |
Arm/Group Title | FR901228 |
---|---|
Arm/Group Description | 13 mg/m^2 FR901228 by vein (IV) over 4 hours on days 1, 8, and 15 |
Period Title: Overall Study | |
STARTED | 9 |
COMPLETED | 9 |
NOT COMPLETED | 0 |
Baseline Characteristics
Arm/Group Title | FR901228 |
---|---|
Arm/Group Description | 13 mg/m^2 FR901228 by vein (IV) over 4 hours on days 1, 8, and 15 |
Overall Participants | 9 |
Age (Count of Participants) | |
<=18 years |
0
0%
|
Between 18 and 65 years |
4
44.4%
|
>=65 years |
5
55.6%
|
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
66.8
(12.6)
|
Sex: Female, Male (Count of Participants) | |
Female |
1
11.1%
|
Male |
8
88.9%
|
Region of Enrollment (participants) [Number] | |
United States |
9
100%
|
Outcome Measures
Title | Overall Objective Response Rate (Complete Response [CR] and Partial Response [PR]) After 6 Courses of Treatment |
---|---|
Description | International Working Group response for non- Hodgkin's lymphoma: Complete Response (CR) - disappearance all detectable clinical/radiographic evidence of disease and disappearance of all disease-related symptoms (present before therapy) and normalization of those biochemical abnormalities; Partial Response (PR) - ≥50% decrease in sum products of greatest diameters (SPD) of 6 largest dominant nodes or nodal masses, selected by clearly measurable in at least two perpendicular dimensions, from disparate regions of body and no decrease in size of other nodes, liver, or spleen. |
Time Frame | 24 weeks (6 courses of 4 week cycles) |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | FR901228 |
---|---|
Arm/Group Description | 13 mg/m^2 FR901228 by vein (IV) over 4 hours on days 1, 8, and 15 |
Measure Participants | 9 |
Complete Response |
0
0%
|
Partial Response |
1
11.1%
|
Title | Median Progression Free-survival (PFS) |
---|---|
Description | Time to disease progression is defined as the time from registration to documentation of disease progression. |
Time Frame | 2 Years |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | FR901228 |
---|---|
Arm/Group Description | 13 mg/m^2 FR901228 by vein (IV) over 4 hours on days 1, 8, and 15 |
Measure Participants | 9 |
Median (Full Range) [months] |
4
|
Title | Median Overall Survival |
---|---|
Description | Survival time is defined as the time from registration to death due to any cause, measured in months. The distribution of survival time estimated using the method of Kaplan-Meier. |
Time Frame | 5 Years |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | FR901228 |
---|---|
Arm/Group Description | 13 mg/m^2 FR901228 by vein (IV) over 4 hours on days 1, 8, and 15 |
Measure Participants | 9 |
Median (Full Range) [months] |
20
|
Adverse Events
Time Frame | 3 years and 9 months | |
---|---|---|
Adverse Event Reporting Description | ||
Arm/Group Title | FR901228 | |
Arm/Group Description | 13 mg/m^2 FR901228 by vein (IV) over 4 hours on days 1, 8, and 15 | |
All Cause Mortality |
||
FR901228 | ||
Affected / at Risk (%) | # Events | |
Total | / (NaN) | |
Serious Adverse Events |
||
FR901228 | ||
Affected / at Risk (%) | # Events | |
Total | 6/9 (66.7%) | |
Cardiac disorders | ||
Cardiac Arrhythmia | 1/9 (11.1%) | |
Infectious Endocarditis | 1/9 (11.1%) | |
Eye disorders | ||
Diplopia | 1/9 (11.1%) | |
Gastrointestinal disorders | ||
Dysphagia | 1/9 (11.1%) | |
General disorders | ||
Death NOS | 1/9 (11.1%) | |
Non-neutropenic fever | 1/9 (11.1%) | |
Fatigue | 1/9 (11.1%) | |
Infections and infestations | ||
Neutropenia | 1/9 (11.1%) | |
Thrombocytopenia | 2/9 (22.2%) | |
Infection | 1/9 (11.1%) | |
Metabolism and nutrition disorders | ||
Glucose, serum-high | 1/9 (11.1%) | |
Increased Alkaline phosphatase | 1/9 (11.1%) | |
Vascular disorders | ||
DVT, Vascular access-related | 1/9 (11.1%) | |
Other (Not Including Serious) Adverse Events |
||
FR901228 | ||
Affected / at Risk (%) | # Events | |
Total | 9/9 (100%) | |
Blood and lymphatic system disorders | ||
anemia | 7/9 (77.8%) | |
Cardiac disorders | ||
sinus tachycardia | 1/9 (11.1%) | |
Eye disorders | ||
blurry vision | 2/9 (22.2%) | |
Gastrointestinal disorders | ||
nausea | 6/9 (66.7%) | |
constipation | 3/9 (33.3%) | |
diarrhea | 3/9 (33.3%) | |
gastritis | 1/9 (11.1%) | |
hemorrhoids | 1/9 (11.1%) | |
mucositis oral | 1/9 (11.1%) | |
oral pain | 1/9 (11.1%) | |
periodontal disease | 1/9 (11.1%) | |
rectal pain | 1/9 (11.1%) | |
stomach pain | 1/9 (11.1%) | |
vomiting | 3/9 (33.3%) | |
taste alteration | 1/9 (11.1%) | |
General disorders | ||
fatigue | 5/9 (55.6%) | |
fever | 2/9 (22.2%) | |
edema limbs | 2/9 (22.2%) | |
Infections and infestations | ||
infection with normal Absolute neutrophil count (ANC) | 7/9 (77.8%) | |
sinusitis | 1/9 (11.1%) | |
Investigations | ||
weight loss | 2/9 (22.2%) | |
thrombocytopenia | 8/9 (88.9%) | |
alanine aminotransferase (ALT) | 2/9 (22.2%) | |
aspartate aminotransferase (AST) | 3/9 (33.3%) | |
alkaline phosphatase | 3/9 (33.3%) | |
creatinine | 1/9 (11.1%) | |
lymphopenia | 6/9 (66.7%) | |
leukopenia | 3/9 (33.3%) | |
neutropenia | 2/9 (22.2%) | |
Metabolism and nutrition disorders | ||
hyperglycemia | 4/9 (44.4%) | |
anorexia | 2/9 (22.2%) | |
hypocalcemia | 2/9 (22.2%) | |
hypoalbuminemia | 4/9 (44.4%) | |
hyperuricemia | 1/9 (11.1%) | |
hypoglycemia | 1/9 (11.1%) | |
hyperkalemia | 4/9 (44.4%) | |
hypomagnesemia | 2/9 (22.2%) | |
hyponatremia | 2/9 (22.2%) | |
hypophosphatemia | 3/9 (33.3%) | |
Musculoskeletal and connective tissue disorders | ||
myalgia | 3/9 (33.3%) | |
Nervous system disorders | ||
sensory neuropathy | 2/9 (22.2%) | |
dizziness | 2/9 (22.2%) | |
headache | 1/9 (11.1%) | |
Respiratory, thoracic and mediastinal disorders | ||
dyspnea | 1/9 (11.1%) | |
pneumonitis | 1/9 (11.1%) | |
cough | 1/9 (11.1%) | |
Skin and subcutaneous tissue disorders | ||
pruritus | 1/9 (11.1%) | |
Vascular disorders | ||
hypotension | 1/9 (11.1%) | |
thrombosis | 1/9 (11.1%) |
Limitations/Caveats
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.
Results Point of Contact
Name/Title | Dr. Luis E. Fayad / Associate Professor |
---|---|
Organization | MD Anderson Cancer Center |
Phone | 713-792-2860 |
jmdennison@mdanderson.org |
- NCI-2009-00240
- NCI-2009-00240
- 2005-0579
- CDR0000486326
- 2005-0579
- 7869
- P30CA016672
- N01CM62202