Lymphoma
Conditions
Keywords
stage I cutaneous T-cell non-Hodgkin lymphoma, stage II cutaneous T-cell non-Hodgkin lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, stage I mycosis fungoides/Sezary syndrome, stage II mycosis fungoides/Sezary syndrome, stage III mycosis fungoides/Sezary syndrome, stage IV mycosis fungoides/Sezary syndrome, recurrent mycosis fungoides/Sezary syndrome
Brief summary
RATIONALE: Drugs used in chemotherapy, such as liposomal doxorubicin and bexarotene, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bexarotene may also cause cutaneous T-cell lymphoma cells to look more like normal cells, and to grow and spread more slowly. Giving liposomal doxorubicin followed by bexarotene may be an effective treatment for cutaneous T-cell lymphoma. PURPOSE: This phase II trial is studying how well giving liposomal doxorubicin followed by bexarotene works in treating patients with cutaneous T-cell lymphoma.
Detailed description
OBJECTIVES: Primary * Determine the progression-free survival of patients with stage IB-IV cutaneous T-cell lymphoma treated with doxorubicin HCl liposome followed by bexarotene. Secondary * Determine the complete and partial response rate in patients treated with this regimen. OUTLINE: This is an open-label, multicenter study. Patients receive doxorubicin HCl liposome IV over 30-90 minutes once on day 1. Treatment repeats every 2 weeks for 8 courses. Beginning within 4 weeks after the last dose of doxorubicin HCl liposome, patients receive oral bexarotene once daily for at least 16 weeks. Patients who achieve a complete or partial response may continue to receive bexarotene in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for 5 years.
Interventions
DRUGTargretin® (bexarotene)
DRUGpegylated liposomal doxorubicin hydrochloride
Sponsors
National Cancer Institute (NCI)
Tibotec Pharmaceutical Limited
M.D. Anderson Cancer Center
NYU Langone Health
Hackensack Meridian Health
Roswell Park Cancer Institute
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed cutaneous T-cell lymphoma * Stage IB-IV disease * Measurable disease * Newly diagnosed or previously treated disease * No demonstrated resistance to prior bexarotene PATIENT CHARACTERISTICS: Performance status * Karnofsky 60-100% Life expectancy * Not specified Hematopoietic * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 Hepatic * AST and ALT ≤ 2.5 times upper limit of normal (ULN) * Bilirubin \< 1.5 times ULN Renal * Creatinine ≤ 1.5 times ULN Cardiovascular * Ejection fraction ≥ 50% by MUGA or 2-D echocardiogram * No New York Heart Association class II-IV heart disease * No clinical evidence of congestive heart failure Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 4 weeks after completion of study treatment * No history of hypersensitivity reactions attributed to doxorubicin HCl liposome or its components * No active potentially life-threatening infection * No other acute disease PRIOR CONCURRENT THERAPY: Chemotherapy * See Disease Characteristics * Prior doxorubicin allowed provided the cumulative dose is ≤ 300 mg/m\^2 * Prior epirubicin hydrochloride allowed provided the cumulative dose is ≤ 540 mg/m\^2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression-free Survival | 3 years | CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT * CT scans of chest, abdomen and pelvis for TNM stage IV patients who had positive findings prior to treatment. * CBC with Sézary cell count and/or flow cytometry in patients with Sézary syndrome. * Dermatologic responses will be determined by the Severity-Weighted Assessment Tool (SWAT), a standardized approach to measuring the extent and severity of overall skin disease in patients with CTCL Primary skin tumor assessments were made by the modified Severity-Weighted Assessment Tool (mSWAT) \[12, 13\]; the Composite Assessment of Index Lesion Severity (CA) \[9, 14\] was used a secondary scale. Progression was defined as ≥25% increase in mSWAT skin score and ≥50% increase in the sum of the products of the greatest diameters of involved lymph nodes over baseline for patients with involved lymph nodes with stage IV disease |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Therapeutic Response | 2 years | CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT * CT scans of chest, abdomen and pelvis for TNM stage IV patients who had positive findings prior to treatment. * CBC with Sézary cell count and/or flow cytometry in patients with Sézary syndrome. * Dermatologic responses will be determined by the Severity-Weighted Assessment Tool (SWAT), a standardized approach to measuring the extent and severity of overall skin disease in patients with CTCL Primary skin tumor assessments were made by the modified Severity-Weighted Assessment Tool (mSWAT) \[12, 13\]; the Composite Assessment of Index Lesion Severity (CA) \[9, 14\] was used a secondary scale. Progression was defined as ≥25% increase in mSWAT skin score and ≥50% increase in the sum of the products of the greatest diameters of involved lymph nodes over baseline for patients with involved lymph nodes with stage IV disease |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Doxil and Targretin® (Bexarotene) Patients will be treated with intravenous Doxil® every two weeks for 8 doses (16 weeks). Responses will be assessed. They will then receive Targretin® (bexarotene) orally for at least 16 weeks. Patients who achieve a CR or PR may continue on Targretin® (bexarotene) until relapse. | 37 |
| Total | 37 |
Baseline characteristics
| Characteristic | Doxil and Targretin® (Bexarotene) |
|---|---|
| Age, Continuous | 56 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 22 Participants |
| Region of Enrollment United States | 37 Participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 12 / 37 |
| other Total, other adverse events | 37 / 37 |
| serious Total, serious adverse events | 15 / 37 |
Outcome results
Primary
Median Progression-free Survival
CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT * CT scans of chest, abdomen and pelvis for TNM stage IV patients who had positive findings prior to treatment. * CBC with Sézary cell count and/or flow cytometry in patients with Sézary syndrome. * Dermatologic responses will be determined by the Severity-Weighted Assessment Tool (SWAT), a standardized approach to measuring the extent and severity of overall skin disease in patients with CTCL Primary skin tumor assessments were made by the modified Severity-Weighted Assessment Tool (mSWAT) \[12, 13\]; the Composite Assessment of Index Lesion Severity (CA) \[9, 14\] was used a secondary scale. Progression was defined as ≥25% increase in mSWAT skin score and ≥50% increase in the sum of the products of the greatest diameters of involved lymph nodes over baseline for patients with involved lymph nodes with stage IV disease
Time frame: 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Doxil and Targretin® (Bexarotene) | Median Progression-free Survival | 5 months |
Secondary
Maximum Therapeutic Response
CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT * CT scans of chest, abdomen and pelvis for TNM stage IV patients who had positive findings prior to treatment. * CBC with Sézary cell count and/or flow cytometry in patients with Sézary syndrome. * Dermatologic responses will be determined by the Severity-Weighted Assessment Tool (SWAT), a standardized approach to measuring the extent and severity of overall skin disease in patients with CTCL Primary skin tumor assessments were made by the modified Severity-Weighted Assessment Tool (mSWAT) \[12, 13\]; the Composite Assessment of Index Lesion Severity (CA) \[9, 14\] was used a secondary scale. Progression was defined as ≥25% increase in mSWAT skin score and ≥50% increase in the sum of the products of the greatest diameters of involved lymph nodes over baseline for patients with involved lymph nodes with stage IV disease
Time frame: 2 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Doxil and Targretin® (Bexarotene) | Maximum Therapeutic Response | Clinical Complete Response | 2 Participants |
| Doxil and Targretin® (Bexarotene) | Maximum Therapeutic Response | Partial Response | 12 Participants |
| Doxil and Targretin® (Bexarotene) | Maximum Therapeutic Response | Stable Disease | 6 Participants |
| Doxil and Targretin® (Bexarotene) | Maximum Therapeutic Response | Progressive Disease | 14 Participants |
| Doxil and Targretin® (Bexarotene) | Maximum Therapeutic Response | Not Evaluable | 3 Participants |