Cutaneous T Cell Lymphoma, Peripheral T Cell Lymphoma
Conditions
Keywords
Histone Acetylase, Differentiation, Sezary Syndrome, Mycosis Fungoides, CD 30 Lymphoma
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.
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.
Interventions
DRUGRomidepsin
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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). |
| 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). |
| 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. |
Countries
Australia, United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 47 |
| 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. | 84 |
| Total | 131 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death on study | 1 | 1 |
| Overall Study | Intercurrent illness | 1 | 0 |
| Overall Study | Refused further treatment | 0 | 7 |
| Overall Study | Switched to alternative treatment | 0 | 3 |
Baseline characteristics
| Characteristic | Peripheral T-cell Lymphoma (PTCL) | Cutaneous T-cell Lymphoma (CTCL) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 16 Participants | 27 Participants | 43 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 57 Participants | 88 Participants |
| Age, Continuous | 58.97 years STANDARD_DEVIATION 12.56 | 57.85 years STANDARD_DEVIATION 13.08 | 58.25 years STANDARD_DEVIATION 12.86 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 46 Participants | 80 Participants | 126 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 17 Participants | 21 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 40 Participants | 65 Participants | 105 Participants |
| Region of Enrollment Australia | 8 participants | 29 participants | 37 participants |
| Region of Enrollment United States | 39 participants | 55 participants | 94 participants |
| Sex: Female, Male Female | 22 Participants | 27 Participants | 49 Participants |
| Sex: Female, Male Male | 25 Participants | 57 Participants | 82 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 47 | 5 / 84 |
| other Total, other adverse events | 47 / 47 | 83 / 84 |
| serious Total, serious adverse events | 20 / 47 | 38 / 84 |
Outcome results
Primary
Duration of Response (DOR)
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Peripheral T-cell Lymphoma (PTCL) | Duration of Response (DOR) | Complete Response/Partial Response | 9 Months |
| Peripheral T-cell Lymphoma (PTCL) | Duration of Response (DOR) | Complete Response | 74 Months |
| Cutaneous T-cell Lymphoma (CTCL) | Duration of Response (DOR) | Complete Response/Partial Response | 13.8 Months |
| Cutaneous T-cell Lymphoma (CTCL) | Duration of Response (DOR) | Complete Response | 19.3 Months |
Primary
Number of Participants With a Response
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peripheral T-cell Lymphoma (PTCL) | Number of Participants With a Response | Complete Response + Partial Response | 17 participants |
| Peripheral T-cell Lymphoma (PTCL) | Number of Participants With a Response | Complete Response | 8 participants |
| Peripheral T-cell Lymphoma (PTCL) | Number of Participants With a Response | Partial Response | 9 participants |
| Peripheral T-cell Lymphoma (PTCL) | Number of Participants With a Response | Stable Disease | 5 participants |
| Peripheral T-cell Lymphoma (PTCL) | Number of Participants With a Response | Progressive disease | 18 participants |
| Peripheral T-cell Lymphoma (PTCL) | Number of Participants With a Response | Not Evaluable | 5 participants |
| Cutaneous T-cell Lymphoma (CTCL) | Number of Participants With a Response | Progressive disease | 18 participants |
| Cutaneous T-cell Lymphoma (CTCL) | Number of Participants With a Response | Complete Response + Partial Response | 28 participants |
| Cutaneous T-cell Lymphoma (CTCL) | Number of Participants With a Response | Stable Disease | 32 participants |
| Cutaneous T-cell Lymphoma (CTCL) | Number of Participants With a Response | Complete Response | 5 participants |
| Cutaneous T-cell Lymphoma (CTCL) | Number of Participants With a Response | Not Evaluable | 6 participants |
| Cutaneous T-cell Lymphoma (CTCL) | Number of Participants With a Response | Partial Response | 23 participants |
Secondary
Fold Change in Histone Acetylation
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Peripheral T-cell Lymphoma (PTCL) | Fold Change in Histone Acetylation | 4 hours | 2.99 Fold change |
| Peripheral T-cell Lymphoma (PTCL) | Fold Change in Histone Acetylation | 24 hours | 1.97 Fold change |
| Peripheral T-cell Lymphoma (PTCL) | Fold Change in Histone Acetylation | 48 hours | 0.62 Fold change |
| Cutaneous T-cell Lymphoma (CTCL) | Fold Change in Histone Acetylation | 4 hours | 3.00 Fold change |
| Cutaneous T-cell Lymphoma (CTCL) | Fold Change in Histone Acetylation | 24 hours | 1.78 Fold change |
| Cutaneous T-cell Lymphoma (CTCL) | Fold Change in Histone Acetylation | 48 hours | 1.67 Fold change |
Secondary
Median Number of Cycles of Depsipeptide Administered
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)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Peripheral T-cell Lymphoma (PTCL) | Median Number of Cycles of Depsipeptide Administered | 3 Cycles per patient |
| Cutaneous T-cell Lymphoma (CTCL) | Median Number of Cycles of Depsipeptide Administered | 4.5 Cycles per patient |
Secondary
Multidrug Resistance Protein 1 (MDR1) or ATP-binding Cassette Sub-family B Member 1 (ABCB1) Gene Expression
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Peripheral T-cell Lymphoma (PTCL) | Multidrug Resistance Protein 1 (MDR1) or ATP-binding Cassette Sub-family B Member 1 (ABCB1) Gene Expression | 4 hours | 2.74 Fold change |
| Peripheral T-cell Lymphoma (PTCL) | Multidrug Resistance Protein 1 (MDR1) or ATP-binding Cassette Sub-family B Member 1 (ABCB1) Gene Expression | 24 hours | 1.5 Fold change |
| Peripheral T-cell Lymphoma (PTCL) | Multidrug Resistance Protein 1 (MDR1) or ATP-binding Cassette Sub-family B Member 1 (ABCB1) Gene Expression | 48 hours | 0.545 Fold change |
| Cutaneous T-cell Lymphoma (CTCL) | Multidrug Resistance Protein 1 (MDR1) or ATP-binding Cassette Sub-family B Member 1 (ABCB1) Gene Expression | 4 hours | 1.78 Fold change |
| Cutaneous T-cell Lymphoma (CTCL) | Multidrug Resistance Protein 1 (MDR1) or ATP-binding Cassette Sub-family B Member 1 (ABCB1) Gene Expression | 24 hours | 1.53 Fold change |
| Cutaneous T-cell Lymphoma (CTCL) | Multidrug Resistance Protein 1 (MDR1) or ATP-binding Cassette Sub-family B Member 1 (ABCB1) Gene Expression | 48 hours | 1.205 Fold change |
Secondary
Number of Participants With Adverse Events
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peripheral T-cell Lymphoma (PTCL) | Number of Participants With Adverse Events | 47 participants |
| Cutaneous T-cell Lymphoma (CTCL) | Number of Participants With Adverse Events | 84 participants |
p-value: <0.01Cochran-Armitage trend test
Secondary
Time to Progression
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Peripheral T-cell Lymphoma (PTCL) | Time to Progression | 4.8 Months |
| Cutaneous T-cell Lymphoma (CTCL) | Time to Progression | 6.4 Months |