Depsipeptide to Treat Patients With Cutaneous T-Cell Lymphoma and Peripheral T-Cell Lymphoma
Study Details
Study Description
Brief Summary
Background:
NSC630176 is a depsipeptide fermentation product from Chromobacterium violaceum with potent cytotoxic activity against human tumor cell lines and in vivo efficacy against both human tumor xenografts and murine tumors (1-3).
NSC 630176, herein referred to as depsipeptide, shows a lack of cross resistance with several commonly used cytotoxic agents such as vincristine, 5-fluorouracil, mitomycin C and cyclophosphamide (2). However, it has been defined as a P-glycoprotein (Pgp) substrate by COMPARE analysis of the National Cancer Institute (NCI) drug screen cytotoxicity profile (4).
Depsipeptide is a member of a novel class of antineoplastic agents, the histone deacetylase inhibitors.
In the phase I trial conducted at the National Cancer Institute (NCI), responses were observed at the maximum tolerated dose (MTD) in patients with cutaneous and peripheral T-cell lymphoma.
Objectives:
In patients with cutaneous T-cell lymphoma, the primary end points to be examined are overall response rate, complete response rate and duration of response.
In patients with relapsed peripheral T-cell lymphoma, the endpoints to be examined are overall response rate and complete response rate.
To evaluate the tolerability of depsipeptide with extended cycles of therapy.
Eligibility:
Patients with cutaneous T-cell lymphoma (mycosis fungoides or Sezary syndrome) or other peripheral T-cell lymphomas are eligible.
Design:
Depsipeptide will be administered at 14 mg/m^2, over 4 hours on days 1, 8 and 15.
This trial will accrue in six cohorts; Arm 1, patients with cutaneous T-cell lymphoma who have had less than or equal to two prior cytotoxic chemotherapy regimens; Arm 2, patients with peripheral T-cell lymphoma who have had less than or equal to two prior cytotoxic chemotherapy regimens; Arm 3, patients with cutaneous and peripheral T-cell lymphoma who have had more than two prior cytotoxic chemotherapy regimens; Arm 4, patients with other mature T-cell lymphomas; Arm 5, a replicate arm of arm 1; Arm 6, patients with peripheral T-cell lymphoma who have had more than two prior cytotoxic chemotherapy regimens; Arm 7, patients with cutaneous T cell lymphoma who have received vorinostat.
Dose may be adjusted based on toxicities.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
Background:
NSC630176 is a depsipeptide fermentation product from Chromobacterium violaceum with potent cytotoxic activity against human tumor cell lines and in vivo efficacy against both human tumor xenografts and murine tumors (1-3).
NSC 630176, herein referred to as depsipeptide, shows a lack of cross resistance with several commonly used cytotoxic agents such as vincristine, 5-fluorouracil, mitomycin C and cyclophosphamide (2). However, it has been defined as a P-glycoprotein (Pgp) substrate by COMPARE analysis of the National Cancer Institute (NCI) drug screen cytotoxicity profile (4).
Depsipeptide is a member of a novel class of antineoplastic agents, the histone deacetylase inhibitors.
In the phase I trial conducted at the NCI, responses were observed at the maximum tolerated dose (MTD) in patients with cutaneous and peripheral T-cell lymphoma.
Objectives:
In patients with cutaneous T-cell lymphoma, the primary end points to be examined are overall response rate, complete response rate and duration of response.
In patients with relapsed peripheral T-cell lymphoma, the endpoints to be examined are overall response rate and complete response rate.
To evaluate the tolerability of depsipeptide with extended cycles of therapy.
Eligibility:
Patients with cutaneous T-cell lymphoma (mycosis fungoides or Sezary syndrome) or other peripheral T-cell lymphomas are eligible.
Design:
Depsipeptide will be administered at 14 mg/m^2, over 4 hours on days 1, 8 and 15.
This trial will accrue in six cohorts; Arm 1, patients with cutaneous T-cell lymphoma who have had less than or equal to two prior cytotoxic chemotherapy regimens; Arm 2, patients with peripheral T-cell lymphoma who have had less than or equal to two prior cytotoxic chemotherapy regimens; Arm 3, patients with cutaneous and peripheral T-cell lymphoma who have had more than two prior cytotoxic chemotherapy regimens; Arm 4, patients with other mature T-cell lymphomas; Arm 5, a replicate arm of arm 1; Arm 6, patients with peripheral T-cell lymphoma who have had more than two prior cytotoxic chemotherapy regimens; Arm 7, patients with cutaneous T cell lymphoma who have received vorinostat.
Dose may be adjusted based on toxicities.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Peripheral T-cell Lymphoma (PTCL) Participants received at least one protocol prescribed dose or higher of Romidepsin intravenously at 14mg/m^2 and at 17.5 mg/m^2 on days 1, 8, and 15 of a 28 day cycle. |
Drug: Romidepsin
|
| Experimental: Cutaneous T-cell Lymphoma (CTCL) Participants received at least one protocol prescribed dose or higher of Romidepsin intravenously at 14mg/m^2 and at 17.5 mg/m^2 on days 1, 8, and 15 of a 28 day cycle. |
Drug: Romidepsin
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With a Response [up to 56.5 days]
A rigorous composite assessment was employed with uni-dimensional measurements of skin and visceral disease sites assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) required clearing of all known disease sites. Partial response (PR) required documented response in skin (≥ 30% per RECIST) or lymph nodes (≥ 50% per the International Working Group (IWG) criteria, with response in both compartments for a determination of PR, IWG guidelines. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Progressive disease (PD) is at least a 20% increase in the sum of the target lesions, or the appearance of one or more new lesions. Lymph node disease was assessed bi-dimensionally using the IWG criteria. Bone marrow involvement, as recommended by IWG criteria, and presence of circulating malignant T-cells ascertained by flow cytometry.
- Duration of Response (DOR) [up to 127 months]
DOR is defined as the date response was noted until disease was no longer considered to be responding. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria and the International Working Group Criteria (IWG).Complete response (CR) required clearing of all known disease sites. Partial response (PR) required documented response in skin (≥ 30% per RECIST) or lymph nodes (≥ 50% per the International Working Group (IWG) criteria, with response in both compartments for a determination of PR, IWG guidelines. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Progressive disease (PD) is at least a 20% increase in the sum of the target lesions, or the appearance of one or more new lesions. Lymph node disease was assessed bi-dimensionally using the IWG criteria. Bone marrow involvement, as recommended by IWG criteria, and presence of circulating malignant T-cells ascertained by flow cytometry.
Secondary Outcome Measures
- Number of Participants With Adverse Events [147 months and 5 days]
Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
- Median Number of Cycles of Depsipeptide Administered [83 cycles (i.e., each cycle is 21 days)]
Participants were administered Depsipeptide and cycles (each cycle is 21 days) were monitored from the prescribed dose or higher to determine reductions (if needed) to maintain tolerability.
- Time to Progression [Until disease progression, or 30 days following off study date]
Time to progression is defined from the first day of therapy until documentation of progressive disease. Progressive disease (PD) is at least a 20% increase in the sum of the target lesions, or the appearance of one or more new lesions. Lymph node disease was assessed bi-dimensionally using the International Working Group (IWG) criteria. Bone marrow involvement, as recommended by IWG criteria, and presence of circulating malignant T-cells ascertained by flow cytometry.
- Fold Change in Histone Acetylation [4 hours, 24 hours, and 48 hours after Romidepsin]
Fold change is calculated by dividing the level of histone acetylation in a treated sample (at 4, 24, and 48 hours) measured as intensity on a dot blot immunoassay, divided by the intensity in the pre-treatment sample. We considered a ≥ 2-fold change a measurable difference, and indicative of successful HDAC inhibition by romidepsin (depsipeptide).
- Multidrug Resistance Protein 1 (MDR1) or ATP-binding Cassette Sub-family B Member 1 (ABCB1) Gene Expression [4 hours, 24 hours, and 48 hours after Romidepsin]
Total ribonucleic acid (RNA) was isolated from peripheral blood mononuclear cells or patient tissue biopsies and analyzed by quantitative polymerase chain reaction (qPCR). Expression of MDR-1/ABCB1 was determined by qPCR relative to an RNA standard, then normalized to ribosomal RNA (rRNA). Fold change is calculated by dividing the level of MDR-1 in a treated sample (at 4, 24, and 48 hours) measured by qPCR, divided by MDR-1 in the pre-treatment sample. We considered a ≥ 2-fold change a measurable difference, and indicative of successful HDAC inhibition by romidepsin (depsipeptide).
Eligibility Criteria
Criteria
- INCLUSION CRITERIA:
Based on the Inclusion Criteria outlined below, patients will accrue to one of the cohorts of the trial.
Cohort- chemotherapy regimens allowed. Cohort Status
Cohort 1
Cutaneous T-cell Lymphoma (mycosis fungoides or Sezary syndrome)-2 or fewer. Closed to accrual
Cohort 2
Peripheral T-cell Lymphoma, unspecified, or Anaplastic large cell lymphoma (T and null cell) Primary Cutaneous Type -2 or fewer. Open and accruing
Cohort 3
Cutaneous T-cell Lymphomas or Peripheral T-cell Lymphoma-More than 2. Closed to accrual
Cohort 4
Other Mature T cell Lymphomas-Any number. Open and accruing
Cohort 5
Cutaneous T-cell Lymphoma (mycosis fungoides or Sezary syndrome)-2 or fewer-Cohort 5 is a replicate cohort, identical to #1
Cohort 6
Peripheral T-cell Lymphoma (PTCL), unspecified, or Anaplastic large cell lymphoma (T and null cell) Primary Cutaneous Type-More than 2. Patients with PTCL in cohort 3 migrated to this cohort
Cohort 7
Cutaneous T-cell Lymphoma (mycosis fungoides or Sezary syndrome) Prior vorinostat required-Any number
Patients with cutaneous T-cell lymphoma [CTCL (mycosis fungoides or Sezary syndrome) stage IB to IVB are eligible. Patients with stage IB and IIA should be refractory to, intolerant to, or have reached a six-month or longer response plateau on at least two prior therapies from the following list: psoralen plus ultraviolet A irradiation (PUVA), ultraviolet B (UVB), electron beam therapy (EBT), photophoresis, interferon, systemic cytotoxic chemotherapy, topical nitrogen mustard, or topical carmustine (BCNU). One qualifying prior treatment must have been topical nitrogen mustard, topical carmustine or a phototherapy (UVB, PUVA or EBT). Topical steroids, systemic retinoids or biologicals do not qualify. Patients with stage IB or IIA who are not candidates for topical nitrogen mustard, topical carmustine or phototherapy (UVB, PUVA or EBT) are eligible for enrollment. Patients may not have received more than two systemic cytotoxic chemotherapy regimens. Steroids, retinoids, and biologic agents, will not be considered as systemic cytotoxic chemotherapy. Radiolabeled monoclonal antibody therapy is considered equivalent to a systemic cytotoxic chemotherapy regimen and must be counted toward the two prior systemic cytotoxic regimens. Patients with stage IIB-IVB who have had no more than 2 prior systemic cytotoxic chemotherapeutic regimens are eligible. There is no restriction regarding number of prior topical therapies, skin irradiation, or non-cytotoxic systemic therapies (i.e. PUVA, retinoids or biologic, with the exception of radiolabeled monoclonal antibody therapy) in this patient group. After 24 patients were enrolled in this arm, the arm was closed, and a replicate arm constituted of this same patient population was opened (Cohort 5).
Patients with peripheral T-cell lymphoma (PTCL), unspecified, or anaplastic large cell lymphoma, T and null cell, primary cutaneous type, as defined by the Revised European American Lymphoma (REAL)/World Health Organization (WHO) classification (16-18), who have experienced disease progression after receiving prior standard treatment and who have had no more than 2 prior systemic cytotoxic chemotherapeutic regimens are eligible.
Patients with cutaneous T cell lymphoma (Mycosis fungoides or Sezary Syndrome) or peripheral T cell lymphoma as defined above who have received more than 2 prior systemic therapies and who have experienced disease progression will be included in a third and independent arm. This arm of the protocol was closed to accrual for CTCL with Amendment H.
Patients with mature T cell lymphomas not included above will be enrolled in a fourth arm. These include but are not exclusively limited to: Enteropathy-type T cell lymphoma; Hepatosplenic T-cell lymphoma; Subcutaneous panniculitis-like T cell lymphoma; Angioimmunoblastic T-cell lymphoma; Anaplastic large cell lymphoma. Patients must have experienced disease progression after receiving prior standard treatment. There will be no limit on the number of prior regimens. Primitive T cell neoplasms and T cell leukemias will not be enrolled.
Patients with peripheral T-cell lymphoma, unspecified, or anaplastic large cell lymphoma, T and null cell, primary cutaneous type, as defined by the REAL/WHO classification (16-18), who have experienced disease progression after receiving prior standard treatment and who have had more than 2 prior systemic cytotoxic chemotherapeutic regimens are eligible for enrollment to a sixth arm of the trial.
Patients with cutaneous T cell lymphoma (Mycosis fungoides or Sezary Syndrome) or peripheral T cell lymphoma as defined in #1 who have received any number of prior systemic therapies and who have previously been treated with vorinostat will be included in a third and independent arm. Patients can be enrolled in this arm if they received prior vorinostat and experienced disease progression, subsequent relapse, or had to discontinue to agent due to toxicity.
Disease that is measurable by radiographic imaging, assessing skin lesions, or by quantitating Sezary cell count.
Patients must:
be age greater than or equal to 18 years
have a performance status of Eastern Cooperative Oncology Group (ECOG) 0-2
have no serious or intercurrent illness and have a life expectancy of greater than 12 weeks
give written informed consent
female patients of childbearing potential must have a negative pregnancy test within 4 weeks and must use effective contraception
sexually active males must use effective contraception
Laboratory values (performed less than or equal to 14 days prior to registration):
absolute neutrophil count greater than or equal to 1000/microliter, platelets greater than or equal to l00,000/microliter, bilirubin (total and direct) less than or equal to 1.5x upper limit of normal, and aspartate aminotransferase (AST) less than or equal to 3x upper limit of normal, unless impairment is due to organ involvement by lymphoma, creatinine less than or equal to 1.5x upper limit of normal, or documented creatinine clearance of greater than or equal to 60mL/min
Cardiac studies (performed within 4 weeks of registration):
Ejection fraction of greater than 50% by Echocardiogram or Cardiac magnetic resonance imaging (MRI), or greater than or equal to 45% by multi-gated acquisition scan (MUGA) Scan.
A stable dose (greater than 1 month) of corticosteroids administered for symptom management will not preclude enrollment. Tapering will be initiated following administration of depsipeptide.
EXCLUSION CRITERIA:
Patients with unconfirmed diagnosis, or with B-cell lymphomas will be excluded.
Prior or concurrent malignancies that have not been curatively treated.
Known central nervous system (CNS) lymphoma.
Chemotherapy within 4 weeks, 6 weeks for nitrosoureas or mitomycin C.
Biologics, Immunotherapy within 2 weeks.
Human Immunodeficiency virus (HIV) seropositivity.
Pregnant or breast-feeding patients.
Major surgery within 21 days.
Uncontrolled infection or uncontrolled medical illness.
Patients having received prior histone deacetylase (HDAC) inhibitor therapy for T cell lymphoma will be excluded except for patients eligible to enroll in cohort 7.
Patients with the following cardiac risk factors will be excluded from the study:
Patients with known cardiac abnormalities such as:
Congenital long QT syndrome
Corrected QT interval (QTc) interval greater than 480 milliseconds
Patients who have had a myocardial infarction within 12 months of study entry.
Patients who have active coronary artery disease as, e.g. angina as defined by Canadian Class II-IV
Patients with an electrocardiography (ECG) recorded at screening showing evidence of cardiac ischemia (ST depression of greater than or equal to 2 mm).
Any patient in whom coronary artery disease is suspected should be referred for a cardiology consultation and if active myocardial ischemia is demonstrated the patient should be excluded. If a noninvasive imaging study is equivocal, it may be necessary to proceed to coronary angiography.
Patients with congestive heart failure that meets New York Heart Association (NYHA) Class II to IV definitions and/or ejection fraction less than 45% by MUGA scan or less than 50% by echocardiogram and/or MRI.
Patients with a history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD). Patients with a history of arrhythmia should have Holter monitoring and evaluation by cardiology.
Patients with dilated, hypertrophic, or restrictive cardiomyopathy from prior treatment or other causes (in doubt, see ejection fraction criteria above). Patients with left ventricular hypertrophy should be discussed with the Principal Investigator or Study Chairman.
Patients with uncontrolled hypertension, i.e., systolic blood pressure (SBP) greater than or equal to 160 mm Hg or diastolic blood pressure (DBP) greater than or equal to 95 mm Hg.
Patients with cardiac arrhythmia requiring anti-arrhythmic medication other than beta blocker or calcium channel blocker. Patients in whom digitalis cannot be discontinued are excluded from study.
Patients with Mobitz II second degree heart block who do not have a pacemaker. Patients with first degree or Mobitz I second degree heart block, bradyarrhythmias or sick sinus syndrome require Holter monitoring and evaluation by cardiology.
Patients with other cardiac disease may be excluded at the discretion of the principal investigator (PI) following consultation with cardiology.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic Scottsdale | Scottsdale | Arizona | United States | 85259 |
| 2 | University of Arkansas | Little Rock | Arkansas | United States | 72205 |
| 3 | City of Hope National Cancer Center | Duarte | California | United States | 91010 |
| 4 | Mercy General Hospital | Sacramento | California | United States | 95819 |
| 5 | Georgetown University | Washington | District of Columbia | United States | 20007-2197 |
| 6 | Northwestern University | Chicago | Illinois | United States | 60611 |
| 7 | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | United States | 20892 |
| 8 | North Shore University Hospital | Manhasset | New York | United States | 11030 |
| 9 | University of Pittsburgh | Pittsburgh | Pennsylvania | United States | 15261 |
| 10 | West Virginia University | Morgantown | West Virginia | United States | 26506 |
| 11 | Royal Adelaide Hospital | Adelaide | Australia | ||
| 12 | Peter MacCallum Cancer Centre | Melbourne | Australia | ||
| 13 | Sir Charles Gairdner Hospital | Perth | Australia |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: James Gulley, M.D., National Cancer Institute (NCI)
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Akilov OE, Grant C, Frye R, Bates S, Piekarz R, Geskin LJ. Low-dose electron beam radiation and romidepsin therapy for symptomatic cutaneous T-cell lymphoma lesions. Br J Dermatol. 2012 Jul;167(1):194-7. doi: 10.1111/j.1365-2133.2012.10905.x.
- Bates SE, Zhan Z, Steadman K, Obrzut T, Luchenko V, Frye R, Robey RW, Turner M, Gardner ER, Figg WD, Steinberg SM, Ling A, Fojo T, To KW, Piekarz RL. Laboratory correlates for a phase II trial of romidepsin in cutaneous and peripheral T-cell lymphoma. Br J Haematol. 2010 Jan;148(2):256-67. doi: 10.1111/j.1365-2141.2009.07954.x. Epub 2009 Oct 28.
- Noonan AM, Eisch RA, Liewehr DJ, Sissung TM, Venzon DJ, Flagg TP, Haigney MC, Steinberg SM, Figg WD, Piekarz RL, Bates SE. Electrocardiographic studies of romidepsin demonstrate its safety and identify a potential role for K(ATP) channel. Clin Cancer Res. 2013 Jun 1;19(11):3095-104. doi: 10.1158/1078-0432.CCR-13-0109. Epub 2013 Apr 15.
- Piekarz RL, Frye AR, Wright JJ, Steinberg SM, Liewehr DJ, Rosing DR, Sachdev V, Fojo T, Bates SE. Cardiac studies in patients treated with depsipeptide, FK228, in a phase II trial for T-cell lymphoma. Clin Cancer Res. 2006 Jun 15;12(12):3762-73.
- Ritchie D, Piekarz RL, Blombery P, Karai LJ, Pittaluga S, Jaffe ES, Raffeld M, Janik JE, Prince HM, Bates SE. Reactivation of DNA viruses in association with histone deacetylase inhibitor therapy: a case series report. Haematologica. 2009 Nov;94(11):1618-22. doi: 10.3324/haematol.2009.008607. Epub 2009 Jul 16.
- Woo S, Gardner ER, Chen X, Ockers SB, Baum CE, Sissung TM, Price DK, Frye R, Piekarz RL, Bates SE, Figg WD. Population pharmacokinetics of romidepsin in patients with cutaneous T-cell lymphoma and relapsed peripheral T-cell lymphoma. Clin Cancer Res. 2009 Feb 15;15(4):1496-503. doi: 10.1158/1078-0432.CCR-08-1215.
- 010049
- 01-C-0049
- NCT00020436
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Although 7 cohorts were written in the protocol, the cohorts were consolidated for submission to the Food and Drug Administration (FDA) into the peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL) groups, thus they are presented in this format. |
| Arm/Group Title | Peripheral T-cell Lymphoma (PTCL) | Cutaneous T-cell Lymphoma (CTCL) |
|---|---|---|
| Arm/Group Description | Participants received at least one protocol prescribed dose or higher of Romidepsin intravenously at 14mg/m^2 and at 17.5 mg/m^2 on days 1, 8, and 15 of a 28 day cycle. | Participants received at least one protocol prescribed dose or higher of Romidepsin intravenously at 14mg/m^2 and at 17.5 mg/m^2 on days 1, 8, and 15 of a 28 day cycle. |
| Period Title: Overall Study | ||
| STARTED | 47 | 84 |
| COMPLETED | 45 | 73 |
| NOT COMPLETED | 2 | 11 |
Baseline Characteristics
| Arm/Group Title | Peripheral T-cell Lymphoma (PTCL) | Cutaneous T-cell Lymphoma (CTCL) | Total |
|---|---|---|---|
| Arm/Group Description | Participants received at least one protocol prescribed dose or higher of Romidepsin intravenously at 14mg/m^2 and at 17.5 mg/m^2 on days 1, 8, and 15 of a 28 day cycle. | Participants received at least one protocol prescribed dose or higher of Romidepsin intravenously at 14mg/m^2 and at 17.5 mg/m^2 on days 1, 8, and 15 of a 28 day cycle. | Total of all reporting groups |
| Overall Participants | 47 | 84 | 131 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
31
66%
|
57
67.9%
|
88
67.2%
|
| >=65 years |
16
34%
|
27
32.1%
|
43
32.8%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
58.97
(12.56)
|
57.85
(13.08)
|
58.25
(12.86)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
22
46.8%
|
27
32.1%
|
49
37.4%
|
| Male |
25
53.2%
|
57
67.9%
|
82
62.6%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
1
2.1%
|
4
4.8%
|
5
3.8%
|
| Not Hispanic or Latino |
46
97.9%
|
80
95.2%
|
126
96.2%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
3
6.4%
|
0
0%
|
3
2.3%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
4
8.5%
|
17
20.2%
|
21
16%
|
| White |
40
85.1%
|
65
77.4%
|
105
80.2%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
2
2.4%
|
2
1.5%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
39
83%
|
55
65.5%
|
94
71.8%
|
| Australia |
8
17%
|
29
34.5%
|
37
28.2%
|
Outcome Measures
| Title | Number of Participants With a Response |
|---|---|
| Description | A rigorous composite assessment was employed with uni-dimensional measurements of skin and visceral disease sites assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) required clearing of all known disease sites. Partial response (PR) required documented response in skin (≥ 30% per RECIST) or lymph nodes (≥ 50% per the International Working Group (IWG) criteria, with response in both compartments for a determination of PR, IWG guidelines. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Progressive disease (PD) is at least a 20% increase in the sum of the target lesions, or the appearance of one or more new lesions. Lymph node disease was assessed bi-dimensionally using the IWG criteria. Bone marrow involvement, as recommended by IWG criteria, and presence of circulating malignant T-cells ascertained by flow cytometry. |
| Time Frame | up to 56.5 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Two participants were excluded. After further analysis it was determined that the participants did not have PTCL but a different form of lymphoma that was not known at the onset of enrollment. |
| Arm/Group Title | Peripheral T-cell Lymphoma (PTCL) | Cutaneous T-cell Lymphoma (CTCL) |
|---|---|---|
| Arm/Group Description | Participants received at least one protocol prescribed dose or higher of Romidepsin intravenously at 14mg/m^2 and at 17.5 mg/m^2 on days 1, 8, and 15 of a 28 day cycle. | Participants received at least one protocol prescribed dose or higher of Romidepsin intravenously at 14mg/m^2 and at 17.5 mg/m^2 on days 1, 8, and 15 of a 28 day cycle. |
| Measure Participants | 45 | 84 |
| Complete Response + Partial Response |
17
36.2%
|
28
33.3%
|
| Complete Response |
8
17%
|
5
6%
|
| Partial Response |
9
19.1%
|
23
27.4%
|
| Stable Disease |
5
10.6%
|
32
38.1%
|
| Progressive disease |
18
38.3%
|
18
21.4%
|
| Not Evaluable |
5
10.6%
|
6
7.1%
|
| Title | Duration of Response (DOR) |
|---|---|
| Description | DOR is defined as the date response was noted until disease was no longer considered to be responding. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria and the International Working Group Criteria (IWG).Complete response (CR) required clearing of all known disease sites. Partial response (PR) required documented response in skin (≥ 30% per RECIST) or lymph nodes (≥ 50% per the International Working Group (IWG) criteria, with response in both compartments for a determination of PR, IWG guidelines. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Progressive disease (PD) is at least a 20% increase in the sum of the target lesions, or the appearance of one or more new lesions. Lymph node disease was assessed bi-dimensionally using the IWG criteria. Bone marrow involvement, as recommended by IWG criteria, and presence of circulating malignant T-cells ascertained by flow cytometry. |
| Time Frame | up to 127 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Peripheral T-cell Lymphoma (PTCL) | Cutaneous T-cell Lymphoma (CTCL) |
|---|---|---|
| Arm/Group Description | Participants received at least one protocol prescribed dose or higher of Romidepsin intravenously at 14mg/m^2 and at 17.5 mg/m^2 on days 1, 8, and 15 of a 28 day cycle. | Participants received at least one protocol prescribed dose or higher of Romidepsin intravenously at 14mg/m^2 and at 17.5 mg/m^2 on days 1, 8, and 15 of a 28 day cycle. |
| Measure Participants | 47 | 84 |
| Complete Response/Partial Response |
9
|
13.8
|
| Complete Response |
74
|
19.3
|
| Title | Number of Participants With Adverse Events |
|---|---|
| Description | Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module. |
| Time Frame | 147 months and 5 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Peripheral T-cell Lymphoma (PTCL) | Cutaneous T-cell Lymphoma (CTCL) |
|---|---|---|
| Arm/Group Description | Participants received at least one protocol prescribed dose or higher of Romidepsin intravenously at 14mg/m^2 and at 17.5 mg/m^2 on days 1, 8, and 15 of a 28 day cycle. | Participants received at least one protocol prescribed dose or higher of Romidepsin intravenously at 14mg/m^2 and at 17.5 mg/m^2 on days 1, 8, and 15 of a 28 day cycle. |
| Measure Participants | 47 | 84 |
| Number [participants] |
47
100%
|
84
100%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Peripheral T-cell Lymphoma (PTCL), Cutaneous T-cell Lymphoma (CTCL) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.01 |
| Comments | An exact Cochran-Armitage trend test was used to compare the distributions. In view of the large number of tests performed, we only refer to those with P-values <0.01 as statistically significant, with those for which 0.01 <P< 0.05 considered trends. | |
| Method | Cochran-Armitage trend test | |
| Comments | ||
| Title | Median Number of Cycles of Depsipeptide Administered |
|---|---|
| Description | Participants were administered Depsipeptide and cycles (each cycle is 21 days) were monitored from the prescribed dose or higher to determine reductions (if needed) to maintain tolerability. |
| Time Frame | 83 cycles (i.e., each cycle is 21 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Peripheral T-cell Lymphoma (PTCL) | Cutaneous T-cell Lymphoma (CTCL) |
|---|---|---|
| Arm/Group Description | Participants received at least one protocol prescribed dose or higher of Romidepsin intravenously at 14mg/m^2 and at 17.5 mg/m^2 on days 1, 8, and 15 of a 28 day cycle. | Participants received at least one protocol prescribed dose or higher of Romidepsin intravenously at 14mg/m^2 and at 17.5 mg/m^2 on days 1, 8, and 15 of a 28 day cycle. |
| Measure Participants | 47 | 84 |
| Median (Full Range) [Cycles per patient] |
3
|
4.5
|
| Title | Time to Progression |
|---|---|
| Description | Time to progression is defined from the first day of therapy until documentation of progressive disease. Progressive disease (PD) is at least a 20% increase in the sum of the target lesions, or the appearance of one or more new lesions. Lymph node disease was assessed bi-dimensionally using the International Working Group (IWG) criteria. Bone marrow involvement, as recommended by IWG criteria, and presence of circulating malignant T-cells ascertained by flow cytometry. |
| Time Frame | Until disease progression, or 30 days following off study date |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Peripheral T-cell Lymphoma (PTCL) | Cutaneous T-cell Lymphoma (CTCL) |
|---|---|---|
| Arm/Group Description | Participants received at least one protocol prescribed dose or higher of Romidepsin intravenously at 14mg/m^2 and at 17.5 mg/m^2 on days 1, 8, and 15 of a 28 day cycle. | Participants received at least one protocol prescribed dose or higher of Romidepsin intravenously at 14mg/m^2 and at 17.5 mg/m^2 on days 1, 8, and 15 of a 28 day cycle. |
| Measure Participants | 47 | 94 |
| Median (95% Confidence Interval) [Months] |
4.8
|
6.4
|
| Title | Fold Change in Histone Acetylation |
|---|---|
| Description | Fold change is calculated by dividing the level of histone acetylation in a treated sample (at 4, 24, and 48 hours) measured as intensity on a dot blot immunoassay, divided by the intensity in the pre-treatment sample. We considered a ≥ 2-fold change a measurable difference, and indicative of successful HDAC inhibition by romidepsin (depsipeptide). |
| Time Frame | 4 hours, 24 hours, and 48 hours after Romidepsin |
Outcome Measure Data
| Analysis Population Description |
|---|
| Global histone acetylation of all samples at pretreatment was designated as 1; values at other time points for each patient were calculated relative to the corresponding pretreatment value. |
| Arm/Group Title | Peripheral T-cell Lymphoma (PTCL) | Cutaneous T-cell Lymphoma (CTCL) |
|---|---|---|
| Arm/Group Description | Participants received at least one protocol prescribed dose or higher of Romidepsin intravenously at 14mg/m^2 and at 17.5 mg/m^2 on days 1, 8, and 15 of a 28 day cycle. | Participants received at least one protocol prescribed dose or higher of Romidepsin intravenously at 14mg/m^2 and at 17.5 mg/m^2 on days 1, 8, and 15 of a 28 day cycle. |
| Measure Participants | 18 | 29 |
| 4 hours |
2.99
|
3.00
|
| 24 hours |
1.97
|
1.78
|
| 48 hours |
0.62
|
1.67
|
| Title | Multidrug Resistance Protein 1 (MDR1) or ATP-binding Cassette Sub-family B Member 1 (ABCB1) Gene Expression |
|---|---|
| Description | Total ribonucleic acid (RNA) was isolated from peripheral blood mononuclear cells or patient tissue biopsies and analyzed by quantitative polymerase chain reaction (qPCR). Expression of MDR-1/ABCB1 was determined by qPCR relative to an RNA standard, then normalized to ribosomal RNA (rRNA). Fold change is calculated by dividing the level of MDR-1 in a treated sample (at 4, 24, and 48 hours) measured by qPCR, divided by MDR-1 in the pre-treatment sample. We considered a ≥ 2-fold change a measurable difference, and indicative of successful HDAC inhibition by romidepsin (depsipeptide). |
| Time Frame | 4 hours, 24 hours, and 48 hours after Romidepsin |
Outcome Measure Data
| Analysis Population Description |
|---|
| ABCB1 expression of all samples at pretreatment was designated as 1; values at other time points for each patient were calculated relative to the corresponding pretreatment value. |
| Arm/Group Title | Peripheral T-cell Lymphoma (PTCL) | Cutaneous T-cell Lymphoma (CTCL) |
|---|---|---|
| Arm/Group Description | Participants received at least one protocol prescribed dose or higher of Romidepsin intravenously at 14mg/m^2 and at 17.5 mg/m^2 on days 1, 8, and 15 of a 28 day cycle. | Participants received at least one protocol prescribed dose or higher of Romidepsin intravenously at 14mg/m^2 and at 17.5 mg/m^2 on days 1, 8, and 15 of a 28 day cycle. |
| Measure Participants | 17 | 35 |
| 4 hours |
2.74
|
1.78
|
| 24 hours |
1.5
|
1.53
|
| 48 hours |
0.545
|
1.205
|
Adverse Events
| Time Frame | 147 months and 5 days | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Although 7 cohorts were written in the protocol, the cohorts were consolidated for submission to the Food and Drug Administration (FDA) into the peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL) groups, thus they are presented in this format. | |||
| Arm/Group Title | Peripheral T-cell Lymphoma (PTCL) | Cutaneous T-cell Lymphoma (CTCL) | ||
| Arm/Group Description | Participants received at least one protocol prescribed dose or higher of Romidepsin intravenously at 14mg/m^2 and at 17.5 mg/m^2 on days 1, 8, and 15 of a 28 day cycle. | Participants received at least one protocol prescribed dose or higher of Romidepsin intravenously at 14mg/m^2 and at 17.5 mg/m^2 on days 1, 8, and 15 of a 28 day cycle. | ||
All Cause Mortality |
||||
| Peripheral T-cell Lymphoma (PTCL) | Cutaneous T-cell Lymphoma (CTCL) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/47 (12.8%) | 5/84 (6%) | ||
Serious Adverse Events |
||||
| Peripheral T-cell Lymphoma (PTCL) | Cutaneous T-cell Lymphoma (CTCL) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 20/47 (42.6%) | 38/84 (45.2%) | ||
| Blood and lymphatic system disorders | ||||
| ANC (absolute neutrophil count) | 0/47 (0%) | 0 | 2/84 (2.4%) | 2 |
| Hemolysis | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Platelet | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Cardiac disorders | ||||
| Death/Cardiac arrest | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Cardiac troponin T | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Hypotension | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| SVT (supraventricular tachycardia) | 1/47 (2.1%) | 1 | 2/84 (2.4%) | 2 |
| Ventricular arrhythmia | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Prolonged QTc | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Anorexia | 0/47 (0%) | 0 | 2/84 (2.4%) | 2 |
| Surgery:GI (gastrointestinal) intussusception | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Ileus | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Melana | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Vomiting | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| General disorders | ||||
| Fatigue | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Death/Fever/Neutropenia | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Fever/neutropenia | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Fever without neutropenia | 0/47 (0%) | 0 | 2/84 (2.4%) | 2 |
| Death related to 2nd cancer:EBV (Epstein Barr virus) lymphoma | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Death:cardiac arrest | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Death progressive disease | 4/47 (8.5%) | 4 | 3/84 (3.6%) | 3 |
| Hepatobiliary disorders | ||||
| Bili increased | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Infections and infestations | ||||
| Catheter-related infection | 0/47 (0%) | 0 | 2/84 (2.4%) | 2 |
| Infection: EBV (Epstein Barr virus) reactivation | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Death/Infection with unknown ANC (absolute neutrophil count) | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Death/Infection without neutropenia | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Infection without neutropenia | 4/47 (8.5%) | 4 | 21/84 (25%) | 25 |
| Infection with grade 3 or 4 neutropenia | 0/47 (0%) | 0 | 3/84 (3.6%) | 3 |
| Infection with unknown ANC | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Infection: septic arthritis | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Febrile neutropenia | 4/47 (8.5%) | 4 | 0/84 (0%) | 0 |
| Infection with grade 3 or 4 ANC | 2/47 (4.3%) | 2 | 0/84 (0%) | 0 |
| Infection:catheter | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Tumor flare | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Nervous system disorders | ||||
| Confusion | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Syncope | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Peripheral motor neuropathy | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Death/ARDS (acute respiratory distress syndrome) | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| DOE (dyspnea on exertion) | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Pleural effusion | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Pneumonitis | 2/47 (4.3%) | 2 | 0/84 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Rash desquamation | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Wound infectious | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Vascular disorders | ||||
| Thromboembolic event | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Peripheral T-cell Lymphoma (PTCL) | Cutaneous T-cell Lymphoma (CTCL) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 47/47 (100%) | 83/84 (98.8%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 38/47 (80.9%) | 151 | 53/84 (63.1%) | 166 |
| Lymphocyte count | 0/47 (0%) | 0 | 42/84 (50%) | 149 |
| Neutrophil count | 0/47 (0%) | 0 | 44/84 (52.4%) | 172 |
| Platelet count decreased | 36/47 (76.6%) | 244 | 48/84 (57.1%) | 300 |
| Activated PTT (partial thromboplastin time) | 0/47 (0%) | 0 | 5/84 (6%) | 7 |
| Hemolysis | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| WBC (white blood cell) decreased | 31/47 (66%) | 195 | 35/84 (41.7%) | 136 |
| Lymphocyte count decreased | 26/47 (55.3%) | 105 | 0/84 (0%) | 0 |
| Neutrophil count decreased | 35/47 (74.5%) | 211 | 0/84 (0%) | 0 |
| Partial thromboplastin time (PTT) | 2/47 (4.3%) | 3 | 0/84 (0%) | 0 |
| Cardiac disorders | ||||
| Hypotension | 12/47 (25.5%) | 39 | 19/84 (22.6%) | 42 |
| Cardiac disorder:T wave | 40/47 (85.1%) | 514 | 57/84 (67.9%) | 424 |
| Phlebitis | 0/47 (0%) | 0 | 4/84 (4.8%) | 4 |
| Conduction disorder | 0/47 (0%) | 0 | 3/84 (3.6%) | 3 |
| Electrocardiogram QT corrected interval prolonged | 0/47 (0%) | 0 | 4/84 (4.8%) | 4 |
| Hypertension | 1/47 (2.1%) | 3 | 3/84 (3.6%) | 3 |
| Palpitations | 1/47 (2.1%) | 2 | 4/84 (4.8%) | 4 |
| Peripheral ischemia | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Sinus bradycardia | 4/47 (8.5%) | 4 | 2/84 (2.4%) | 2 |
| Sinus tachycardia | 0/47 (0%) | 0 | 2/84 (2.4%) | 2 |
| SVT (supraventricular tachycardia) | 2/47 (4.3%) | 3 | 3/84 (3.6%) | 5 |
| Ventricular arrhythmia | 3/47 (6.4%) | 5 | 2/84 (2.4%) | 3 |
| Troponin I increased | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Troponin T increased | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Pericardial effusion | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Congenital, familial and genetic disorders | ||||
| Alkalosis | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Ear and labyrinth disorders | ||||
| Ear pain | 2/47 (4.3%) | 2 | 5/84 (6%) | 8 |
| Endocrine disorders | ||||
| Hot flashes | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Eye disorders | ||||
| Blurred vision | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Cataract | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Conjunctivitis | 1/47 (2.1%) | 1 | 1/84 (1.2%) | 1 |
| Eye disorder | 0/47 (0%) | 0 | 6/84 (7.1%) | 6 |
| Eye pain | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Keratitis | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Vision changes | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Watering eyes | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Dry eye | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Anorexia | 31/47 (66%) | 124 | 37/84 (44%) | 79 |
| Constipation | 17/47 (36.2%) | 29 | 33/84 (39.3%) | 61 |
| Nausea | 38/47 (80.9%) | 224 | 67/84 (79.8%) | 266 |
| Dysgeusia | 20/47 (42.6%) | 86 | 27/84 (32.1%) | 54 |
| Diarrhea | 17/47 (36.2%) | 82 | 24/84 (28.6%) | 44 |
| Vomiting | 23/47 (48.9%) | 101 | 40/84 (47.6%) | 101 |
| Abdominal pain | 7/47 (14.9%) | 8 | 7/84 (8.3%) | 14 |
| Bloating | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Dehydration | 4/47 (8.5%) | 8 | 8/84 (9.5%) | 11 |
| Dry mouth | 1/47 (2.1%) | 1 | 4/84 (4.8%) | 5 |
| Dyspepsia on exertion | 0/47 (0%) | 0 | 6/84 (7.1%) | 7 |
| Dysphagia | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Esophagitis | 0/47 (0%) | 0 | 2/84 (2.4%) | 2 |
| GERD (gastroesophageal reflux disease) | 0/47 (0%) | 0 | 4/84 (4.8%) | 4 |
| Ileus | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Lower GI hemorrhage | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Mucositis oral | 4/47 (8.5%) | 4 | 6/84 (7.1%) | 9 |
| Oral pain/mucositis | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Rectal hemorrhage | 0/47 (0%) | 0 | 2/84 (2.4%) | 2 |
| Pancreatitis | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Dyspepsia | 5/47 (10.6%) | 7 | 0/84 (0%) | 0 |
| General disorders | ||||
| Fatigue | 34/47 (72.3%) | 129 | 68/84 (81%) | 194 |
| Fever | 18/47 (38.3%) | 50 | 20/84 (23.8%) | 45 |
| Chills | 4/47 (8.5%) | 4 | 6/84 (7.1%) | 10 |
| Pain | 10/47 (21.3%) | 24 | 21/84 (25%) | 25 |
| Weight gain | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Weight loss | 6/47 (12.8%) | 6 | 11/84 (13.1%) | 15 |
| Hepatobiliary disorders | ||||
| Hypoalbuminemia | 32/47 (68.1%) | 146 | 36/84 (42.9%) | 89 |
| Bilirubin increased | 11/47 (23.4%) | 76 | 18/84 (21.4%) | 44 |
| AST (aspartate transaminase)/SGOT (serum glutamic oxaloacetic transaminase) | 17/47 (36.2%) | 58 | 0/84 (0%) | 0 |
| ALT (alanine aminotransferase) | 0/47 (0%) | 0 | 22/84 (26.2%) | 45 |
| Alk phos | 0/47 (0%) | 0 | 11/84 (13.1%) | 23 |
| AST (aspartate aminotransferase) | 0/47 (0%) | 0 | 26/84 (31%) | 68 |
| GGT (gamma glutamyltransferase) increased | 0/47 (0%) | 0 | 4/84 (4.8%) | 9 |
| Viral hepatitis | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| ALT(alanine aminotransferase)/SGPT (serum glutamic pyruvic transaminase) | 15/47 (31.9%) | 53 | 0/84 (0%) | 0 |
| Alkaline phosphokinase increased | 5/47 (10.6%) | 8 | 0/84 (0%) | 0 |
| Immune system disorders | ||||
| Allergic reaction | 1/47 (2.1%) | 1 | 4/84 (4.8%) | 6 |
| Allergic rhinitis | 4/47 (8.5%) | 22 | 6/84 (7.1%) | 11 |
| Anaphylaxis | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Infections and infestations | ||||
| Catheter-related infection | 2/47 (4.3%) | 2 | 5/84 (6%) | 5 |
| Febrile neutropenia | 0/47 (0%) | 0 | 2/84 (2.4%) | 3 |
| Infections | 18/47 (38.3%) | 38 | 22/84 (26.2%) | 75 |
| Lung infection | 0/47 (0%) | 0 | 2/84 (2.4%) | 2 |
| Tooth infection | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Acute kidney injury | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Wound dehiscence | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Investigations | ||||
| INR (International Normalized Ratio) increased | 2/47 (4.3%) | 2 | 4/84 (4.8%) | 11 |
| Metabolism and nutrition disorders | ||||
| Hyperglycemia | 28/47 (59.6%) | 127 | 33/84 (39.3%) | 109 |
| Hypokalemia | 14/47 (29.8%) | 19 | 14/84 (16.7%) | 35 |
| Hypermagnesemia | 11/47 (23.4%) | 67 | 21/84 (25%) | 71 |
| Hyperuricemia | 16/47 (34%) | 86 | 25/84 (29.8%) | 71 |
| Hyponatremia | 15/47 (31.9%) | 27 | 14/84 (16.7%) | 26 |
| Hypocalcemia | 34/47 (72.3%) | 142 | 37/84 (44%) | 134 |
| Hypophosphatemia | 17/47 (36.2%) | 55 | 0/84 (0%) | 0 |
| Hypomagnesemia | 16/47 (34%) | 52 | 24/84 (28.6%) | 68 |
| Acidosis | 1/47 (2.1%) | 1 | 1/84 (1.2%) | 1 |
| Cholesterol high | 1/47 (2.1%) | 1 | 4/84 (4.8%) | 8 |
| CPK (creatine phosphokinase) | 5/47 (10.6%) | 6 | 11/84 (13.1%) | 20 |
| Hypercalcemia | 6/47 (12.8%) | 18 | 5/84 (6%) | 37 |
| Hyperkalemia | 6/47 (12.8%) | 15 | 8/84 (9.5%) | 13 |
| Hypernatremia | 3/47 (6.4%) | 7 | 3/84 (3.6%) | 7 |
| Hypertriglyceridemia | 3/47 (6.4%) | 3 | 1/84 (1.2%) | 1 |
| Hypoglycemia | 8/47 (17%) | 11 | 9/84 (10.7%) | 23 |
| Hypophosphatemia | 0/47 (0%) | 0 | 16/84 (19%) | 45 |
| Serum amylase increased | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Lipase increased | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 0/47 (0%) | 0 | 6/84 (7.1%) | 9 |
| Arthritis | 1/47 (2.1%) | 1 | 1/84 (1.2%) | 1 |
| Musculoskeletal and connective tissue disorder | 0/47 (0%) | 0 | 7/84 (8.3%) | 21 |
| Myalgia | 8/47 (17%) | 10 | 5/84 (6%) | 8 |
| Non cardiac chest pain | 4/47 (8.5%) | 6 | 5/84 (6%) | 6 |
| Arthralgia | 3/47 (6.4%) | 4 | 0/84 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Tumor flare | 1/47 (2.1%) | 1 | 7/84 (8.3%) | 9 |
| Nervous system disorders | ||||
| Headache | 17/47 (36.2%) | 32 | 18/84 (21.4%) | 33 |
| Anxiety | 0/47 (0%) | 0 | 7/84 (8.3%) | 10 |
| Depression | 4/47 (8.5%) | 4 | 6/84 (7.1%) | 6 |
| Dizziness | 5/47 (10.6%) | 5 | 8/84 (9.5%) | 15 |
| Insomnia | 4/47 (8.5%) | 4 | 5/84 (6%) | 7 |
| Neuralgia | 1/47 (2.1%) | 1 | 1/84 (1.2%) | 1 |
| Paresthesia | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Peripheral sensory neuropathy | 4/47 (8.5%) | 4 | 7/84 (8.3%) | 8 |
| Psychosis | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Syncope | 1/47 (2.1%) | 1 | 3/84 (3.6%) | 5 |
| Tremor | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Memory impairment | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Peripheral motor neuropathy | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Confusion | 2/47 (4.3%) | 2 | 0/84 (0%) | 0 |
| Euphoria | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Extrapyramidal disorder | 3/47 (6.4%) | 4 | 0/84 (0%) | 0 |
| Anxiety | 2/47 (4.3%) | 9 | 0/84 (0%) | 0 |
| Ataxia | 2/47 (4.3%) | 2 | 0/84 (0%) | 0 |
| Renal and urinary disorders | ||||
| Creatinine increased | 10/47 (21.3%) | 26 | 11/84 (13.1%) | 14 |
| Hematuria | 2/47 (4.3%) | 3 | 1/84 (1.2%) | 1 |
| Proteinuria | 1/47 (2.1%) | 1 | 1/84 (1.2%) | 1 |
| UTI (urinary tract infection) | 0/47 (0%) | 0 | 6/84 (7.1%) | 14 |
| Urinary frequency | 0/47 (0%) | 0 | 2/84 (2.4%) | 2 |
| Urinary retention | 1/47 (2.1%) | 1 | 4/84 (4.8%) | 5 |
| Urine incontinence | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Reproductive system and breast disorders | ||||
| Erectile dysfunction | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Vaginal mucositis | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Bronchopulmonary hemorrhage | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Cough | 8/47 (17%) | 12 | 7/84 (8.3%) | 17 |
| Dyspnea | 5/47 (10.6%) | 7 | 13/84 (15.5%) | 19 |
| Epistaxis | 3/47 (6.4%) | 5 | 2/84 (2.4%) | 2 |
| Hypoxia | 3/47 (6.4%) | 3 | 5/84 (6%) | 5 |
| Nasal congestion | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Pleural effusion | 0/47 (0%) | 0 | 3/84 (3.6%) | 3 |
| Pulmonary fibrosis | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| URI (upper respiratory infection) | 0/47 (0%) | 0 | 5/84 (6%) | 6 |
| Voice alteration/hoarseness | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Wheezing | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Pneumonitis | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 0/47 (0%) | 0 | 2/84 (2.4%) | 2 |
| Dry skin | 2/47 (4.3%) | 2 | 4/84 (4.8%) | 4 |
| Erythema multiforme | 1/47 (2.1%) | 1 | 1/84 (1.2%) | 1 |
| Flushing | 2/47 (4.3%) | 7 | 3/84 (3.6%) | 3 |
| Hyperhidrosis | 2/47 (4.3%) | 3 | 2/84 (2.4%) | 3 |
| Nail loss | 1/47 (2.1%) | 1 | 1/84 (1.2%) | 1 |
| Pruritis | 12/47 (25.5%) | 14 | 22/84 (26.2%) | 35 |
| Rash-maculo-papular | 12/47 (25.5%) | 15 | 23/84 (27.4%) | 26 |
| Stevens-Johnson syndrome | 0/47 (0%) | 0 | 1/84 (1.2%) | 1 |
| Skin decubitus ulcer | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Rash acneiform | 1/47 (2.1%) | 1 | 0/84 (0%) | 0 |
| Injection site reaction | 5/47 (10.6%) | 8 | 4/84 (4.8%) | 4 |
| Vascular disorders | ||||
| Thromboembolic event | 1/47 (2.1%) | 1 | 4/84 (4.8%) | 4 |
Limitations/Caveats
More Information
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
| Name/Title | Dr. Kieron Dunleavy |
|---|---|
| Organization | National Cancer Institute |
| Phone | 301-435-1007 |
| DunleavK@mail.nih.gov |
- 010049
- 01-C-0049
- NCT00020436