Peripheral T-Cell Lymphoma
Conditions
Brief summary
This study examines the use of denileukin diftitox (Ontak) for patients with peripheral T-cell lymphoma who are candidates for autologous stem cell transplants.
Detailed description
This protocol proposes first to increase the proportion of patients who achieve adequate initial disease control and are able to proceed to autologous stem cell transplant (ASCT) in first complete or partial remission. It administers intensive and novel induction therapy. Two cycles of gemcitabine, vinorelbine, Doxil (GND) will be used followed by two cycles of augmented dose Cyclophosphamide (CHOP) plus high-dose methotrexate (MTX). Patients will be restaged after two cycles of GND to assess response to GND alone and again after the second cycle of augmented CHOP/high-dose MTX. Those achieving a remission status will receive intensive consolidation with HiDAC/etoposide followed by stem cell mobilization. A five-day course of denileukin diftitox (Ontak) will be administered at and will serve as an in vivo purge. This will be followed by autologous stem cell transplant. Those not achieving partial remission or better following the four induction courses will receive 2 cycles of denileukin diftitox(Ontak) for 5 days. Those achieving partial remission or better to this regimen will go on to consolidation/mobilization and autologous stem cell transplant. Post-transplant, denileukin diftitox will also be used as an additional module of therapy.
Interventions
DRUGGemcitabine
Chemotherapy medication used to treat a number of types of cancer
DRUGNavelbine
Navelbine is an chemotherapy medication used to treat a number of types of cancer
Doxorubicin Hydrochloride Liposome Injection is an anti-cancer chemotherapy drug
G-CSF is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream.
DRUGPegfilgrastim
Colony-stimulating factor 3 (CSF 3) and, is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream. May be used instead of G-CSF
DRUGCyclophosphamide
Cancer medication that interferes with the growth and spread of cancer cells in the body
DRUGVincristine
Vincristine is a chemotherapy medication used to treat cancer. Vincristine works by stopping the cancer cells from separating into 2 new cells to stops the growth of the cancer
DRUGLeucovorin
Leucovorin is used to prevent harmful effects of methotrexate when methotrexate is used to treat certain types of cancer.
DRUGMethotrexate
Methotrexate is a chemotherapy medication used to treat cancer
DRUGDoxorubicin Hydrochloride
Doxorubicin Hydrochloride is a chemotherapy medication used to treat cancer
DRUGCytarabine
Medication used to treat acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and non-Hodgkin's lymphoma
DRUGEtoposide
Etoposide is a is a chemotherapy medication used to treat cancer
DRUGCarmustine
Carmustine is a chemotherapy medication used to treat cancer
Denileukin diftitox is an antineoplastic agent, an engineered protein combining Interleukin-2 and Diphtheria toxin. Denileukin diftitox could bind to Interleukin-2 receptors and introduce the diphtheria toxin into cells that express those receptors, killing the cells
Sponsors
Eisai Inc.
Washington University School of Medicine
University of California, San Francisco
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Histologic diagnosis of any of the following: * Peripheral T-cell lymphoma not otherwise specified (PTCL-U),(IPI \>2) * Angioimmunoblastic T-cell lymphoma (AILT) (IPI \>2) * Non-primary cutaneous Alk-1-negative anaplastic large cell lymphoma * Extranodal natural killer (NK)/T lymphoma (Excluding stage I/II nasal disease) * Blastic NK cell lymphoma * Enteropathy type T-cell lymphoma * Cutaneous panniculitis-like T-cell lymphoma * Hepatosplenic T-cell lymphoma * Measurable or assessable disease is not required. * Age ≥ 18 and ≤ 70 years * Previously untreated or 1 prior cycle of chemotherapy * Creatinine \< 2.0 mg/dL * Total bilirubin \< 2.0 mg/dL, aspartate aminotransferase (AST) \< 3x upper limit of normal * Patients who test positive for Hepatitis B surface Ag (HepBSAg) or Hepatitis C antibody (HepCAb) are eligible provided all of the following criteria are met: * bilirubin ≤ 2 x upper limit of normal; * aspartate aminotransferase (AST) ≤ 3 x upper limit of normal; * liver biopsy demonstrates ≤ grade 2 fibrosis and no cirrhosis. Hepatitis B surface Ag(+) patients will be treated with lamivudine (3TC) or investigator's preferred antiviral regimen throughout protocol therapy and for 6-12 months thereafter. * Neutrophils ≥ 1000/microlitre (uL) platelets \> 100,000/uL * HIV-negative * Left ventricular ejection fraction (LVEF) of ≥ 45% * No known hypersensitivity to denileukin diftitox or any of its components: diptheria toxin, interleukin-2, or excipients * Non-pregnant, non-nursing: Treatment under this protocol would expose an unborn child to significant risks. Women and men of reproductive potential should agree to use an effective means of birth control. * Patients with a currently active second malignancy, other than non-melanoma skin cancers are not eligible. (This includes Waldenstrom's Macroglobulinemia, since such patents have experienced transient increases inImmunoglobulin M (IgM) following initiation of rituximab, with the potential for hyperviscosity syndrome requiring plasmapheresis). Patients are not considered to have a currently active malignancy if they have completed anti-cancer therapy, and are considered by their physician to be at less than 30% risk of relapse.
Exclusion criteria
* PTCL-U / AILT with IPI 0 or 1 Extranodal NK/T nasal stage I/II T-lymphoblastic lymphoma Adult T-cell leukemia/lymphoma * Adult T-cell leukemia/lymphoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Up to 3 years | Progression-Free Survival will be defined the percentage of participants alive and progression-free at median follow up of 25 months. Patients will be routinely followed for disease progression and those who die without a reported prior progression will be considered to have progressed on the day of their death. Patients who did not progress or die will be censored at the day of their last treatment assessment. Patients who have not received study regimen or did not have on-study treatment assessments will be censored on the day they entered the trial. Patients who receive chemotherapy for reasons other than documented progression of disease or clinical progression without documented progression will be censored on the earliest date of subsequent therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival Rate | Up to 5 years | Overall Survival will be defined the percentage of participants alive at median follow up of 25 months. If the patient is lost to follow-up, survival will be censored on the last date the patient was known to be alive. The analysis is expected to occur up to 60 months after the first patient is entered the trial. |
| Complete Response Rate | Up to 3 years | The complete response rate will be defined as the total number of patients who have defined complete response using study regimen (intensive induction therapy/progressive chemotherapy/stem cell rescue), divided by the number of patients entered in the trial using response-evaluable patients. |
| Median Time to Response | Up to 2 years | The time to response is measured from the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started) in months. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Plan (1) Induction Chemo A; Two 21-day cycles of Gemcitabine 1000 mg/m2 days 1, 8, Navelbine 20 mg/m2 day 1, 8; Doxil 15 mg/m2 Days 1, 8, Granulocyte-colony stimulating factor(G-CSF) Days 4-6 and 10-15 (2) Induction Chemo B: Two 21-day cycles of Cyclophosphamide 2000 mg/m2 day 1; Doxorubicin 50 mg/m2 day 1; Vincristine 1.4 mg/m2 day 1; Prednisone 100 mg/m2 days 1-5; Methotrexate 3000 mg/m2 IV over 4h day 15; Leucovorin rescue (3) Disease Evaluation (4) High-dose Consolidation Chemo, high dose Ara-C, Denileukin diftitox (Ontak) and Stem Cell Collection (5) Consolidation Cytarabine 2000 mg/m2 IV over 2 h q 12h days 1-4, Etoposide 40 mg/m2 continuous intravenous infusion days 1-4, Denileukin Diftitox (Ontak) 9 mcg/kg/day days 6-10, G-CSF 10 mcg/kg/day day 14+, Stem cell collection day 22 (6) Autologous Stem Cell Transplant Carmustine 550 mg/m2 day 1-6, Etoposide 60 mg/kg IV over 4h day -4, Cyclophosphamide 100 mg/kg day -2, Stem cell infusion day 0 (7) Post-transplant: Denileukin diftitox | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Death | 2 |
| Overall Study | Excluded after GVD (Not evaluable) | 2 |
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Treatment Plan |
|---|---|
| Age, Continuous | 58 years |
| Disease Stage Stage III | 7 Participants |
| Disease Stage Stage I/II | 0 Participants |
| Disease Stage Stage IV | 14 Participants |
| Extranodal Sites Bone | 3 Participants |
| Extranodal Sites Bone Marrow | 7 Participants |
| Extranodal Sites Gastrointestinal | 2 Participants |
| Extranodal Sites Liver | 1 Participants |
| Extranodal Sites Lung | 1 Participants |
| Extranodal Sites No extranodal site | 3 Participants |
| Extranodal Sites Skin | 3 Participants |
| Extranodal Sites Thyroid | 1 Participants |
| Histology Anaplastic large cell lymphoma, ALK- | 1 Participants |
| Histology Angioimmunoblastic T-cell lymphoma (AILT) | 8 Participants |
| Histology Enteropathy-associated T-cell lymphoma | 1 Participants |
| Histology Hepato-Splenic gamma-delta T-cell Lymphoma | 1 Participants |
| Histology Peripheral T-cell lymphoma (PTCL) not classified | 9 Participants |
| Histology Subcutaneous panniculitis-like T-cell Lymphoma | 1 Participants |
| International prognostic index (IPI) score Score of 2 | 6 Participants |
| International prognostic index (IPI) score Score of 3 | 12 Participants |
| International prognostic index (IPI) score Score of >=4 | 3 Participants |
| Lactate Dehydrogenase (LDH)> normal | 19 Participants |
| Region of Enrollment United States | 21 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 21 |
| other Total, other adverse events | 11 / 21 |
| serious Total, serious adverse events | 21 / 21 |
Outcome results
Primary
Progression Free Survival
Progression-Free Survival will be defined the percentage of participants alive and progression-free at median follow up of 25 months. Patients will be routinely followed for disease progression and those who die without a reported prior progression will be considered to have progressed on the day of their death. Patients who did not progress or die will be censored at the day of their last treatment assessment. Patients who have not received study regimen or did not have on-study treatment assessments will be censored on the day they entered the trial. Patients who receive chemotherapy for reasons other than documented progression of disease or clinical progression without documented progression will be censored on the earliest date of subsequent therapy
Time frame: Up to 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Plan | Progression Free Survival | 65 percentage of partcipants |
Secondary
Complete Response Rate
The complete response rate will be defined as the total number of patients who have defined complete response using study regimen (intensive induction therapy/progressive chemotherapy/stem cell rescue), divided by the number of patients entered in the trial using response-evaluable patients.
Time frame: Up to 3 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Plan | Complete Response Rate | 14 Participants |
Secondary
Median Time to Response
The time to response is measured from the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started) in months.
Time frame: Up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Plan | Median Time to Response | 3.0 months |
Secondary
Overall Survival Rate
Overall Survival will be defined the percentage of participants alive at median follow up of 25 months. If the patient is lost to follow-up, survival will be censored on the last date the patient was known to be alive. The analysis is expected to occur up to 60 months after the first patient is entered the trial.
Time frame: Up to 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Plan | Overall Survival Rate | 75 percentage of participants |