Trial Outcomes & Findings for Treatment of PTCL With Aggressive Induction Therapy Followed by Autologous SCT Using Denileukin Diftitox (Ontak) (NCT NCT00632827)
NCT ID: NCT00632827
Last Updated: 2020-04-27
Results Overview
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
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
21 participants
Primary outcome timeframe
Up to 3 years
Results posted on
2020-04-27
Participant Flow
Participant milestones
| Measure |
Treatment Plan
All patients will be given allopurinol 600 mg/day PO on day 1 of induction chemotherapy, and then 300 mg/day.
Patients then receive two cycles of gemcitabine, vinorelbine, Doxil (GVD) followed by two cycles of augmented dose Cyclophosphamide (CHOP) plus high-dose Methotrexate (MTX). Patients were restaged after 2 cycles of GVD and again after the second cycle of augmented CHOP/high-dose MTX.
Those achieving a remission status received intensive consolidation with Idarubicin/cytosine arabinoside(iDAC)/etoposide followed by stem cell mobilization and 5-day course of denileukin diftitox (Ontak) will be administered 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 moved to consolidation/mobilization and autologous stem cell transplant.
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|---|---|
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Overall Study
STARTED
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21
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Overall Study
Received GVD
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21
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Overall Study
Received M-CHOP
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18
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Overall Study
Evaluated Post Stem Cell Transplant
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16
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Overall Study
COMPLETED
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11
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Overall Study
NOT COMPLETED
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10
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Reasons for withdrawal
| Measure |
Treatment Plan
All patients will be given allopurinol 600 mg/day PO on day 1 of induction chemotherapy, and then 300 mg/day.
Patients then receive two cycles of gemcitabine, vinorelbine, Doxil (GVD) followed by two cycles of augmented dose Cyclophosphamide (CHOP) plus high-dose Methotrexate (MTX). Patients were restaged after 2 cycles of GVD and again after the second cycle of augmented CHOP/high-dose MTX.
Those achieving a remission status received intensive consolidation with Idarubicin/cytosine arabinoside(iDAC)/etoposide followed by stem cell mobilization and 5-day course of denileukin diftitox (Ontak) will be administered 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 moved to consolidation/mobilization and autologous stem cell transplant.
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|---|---|
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Overall Study
Excluded after GVD (Not evaluable)
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2
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Overall Study
Death
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2
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Overall Study
Adverse Event
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5
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Overall Study
Lost to Follow-up
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1
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Baseline Characteristics
Treatment of PTCL With Aggressive Induction Therapy Followed by Autologous SCT Using Denileukin Diftitox (Ontak)
Baseline characteristics by cohort
| Measure |
Treatment Plan
n=21 Participants
(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
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|---|---|
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Age, Continuous
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58 years
n=5 Participants
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Sex: Female, Male
Female
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8 Participants
n=5 Participants
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Sex: Female, Male
Male
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13 Participants
n=5 Participants
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Region of Enrollment
United States
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21 participants
n=5 Participants
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Histology
Angioimmunoblastic T-cell lymphoma (AILT)
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8 Participants
n=5 Participants
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Histology
Peripheral T-cell lymphoma (PTCL) not classified
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9 Participants
n=5 Participants
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Histology
Enteropathy-associated T-cell lymphoma
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1 Participants
n=5 Participants
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Histology
Subcutaneous panniculitis-like T-cell Lymphoma
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1 Participants
n=5 Participants
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Histology
Hepato-Splenic gamma-delta T-cell Lymphoma
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1 Participants
n=5 Participants
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Histology
Anaplastic large cell lymphoma, ALK-
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1 Participants
n=5 Participants
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Extranodal Sites
Bone Marrow
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7 Participants
n=5 Participants
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Extranodal Sites
Skin
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3 Participants
n=5 Participants
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Extranodal Sites
Bone
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3 Participants
n=5 Participants
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Extranodal Sites
Gastrointestinal
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2 Participants
n=5 Participants
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Extranodal Sites
Lung
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1 Participants
n=5 Participants
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Extranodal Sites
Liver
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1 Participants
n=5 Participants
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Extranodal Sites
Thyroid
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1 Participants
n=5 Participants
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Extranodal Sites
No extranodal site
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3 Participants
n=5 Participants
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Disease Stage
Stage I/II
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0 Participants
n=5 Participants
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Disease Stage
Stage III
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7 Participants
n=5 Participants
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Disease Stage
Stage IV
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14 Participants
n=5 Participants
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Lactate Dehydrogenase (LDH)> normal
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19 Participants
n=5 Participants
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International prognostic index (IPI) score
Score of 2
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6 Participants
n=5 Participants
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International prognostic index (IPI) score
Score of 3
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12 Participants
n=5 Participants
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International prognostic index (IPI) score
Score of >=4
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3 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Up to 3 yearsProgression-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
Outcome measures
| Measure |
Treatment Plan
n=21 Participants
(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 and 8, 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 -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 (Ontak) 18 mcg/kg/day days 1- 5
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|---|---|
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Progression Free Survival
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65 percentage of partcipants
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SECONDARY outcome
Timeframe: Up to 5 yearsOverall 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.
Outcome measures
| Measure |
Treatment Plan
n=21 Participants
(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 and 8, 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 -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 (Ontak) 18 mcg/kg/day days 1- 5
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|---|---|
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Overall Survival Rate
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75 percentage of participants
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SECONDARY outcome
Timeframe: Up to 3 yearsThe 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.
Outcome measures
| Measure |
Treatment Plan
n=21 Participants
(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 and 8, 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 -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 (Ontak) 18 mcg/kg/day days 1- 5
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|---|---|
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Complete Response Rate
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14 Participants
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SECONDARY outcome
Timeframe: Up to 2 yearsThe 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.
Outcome measures
| Measure |
Treatment Plan
n=21 Participants
(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 and 8, 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 -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 (Ontak) 18 mcg/kg/day days 1- 5
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|---|---|
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Median Time to Response
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3.0 months
Interval 1.4 to 19.4
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Adverse Events
Treatment Plan
Serious events: 21 serious events
Other events: 11 other events
Deaths: 7 deaths
Serious adverse events
| Measure |
Treatment Plan
n=21 participants at risk
(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 and 8, 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 -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 (Ontak) 18 mcg/kg/day days 1- 5
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|---|---|
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Blood and lymphatic system disorders
Cytopenia
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100.0%
21/21 • Number of events 21 • Up to 5 years
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Blood and lymphatic system disorders
Febrile neutropenia
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52.4%
11/21 • Number of events 11 • Up to 5 years
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Infections and infestations
Sepsis/Bacteremia
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28.6%
6/21 • Number of events 6 • Up to 5 years
|
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Vascular disorders
Capillary leak syndrome
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4.8%
1/21 • Number of events 1 • Up to 5 years
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Renal and urinary disorders
Renal Failure
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4.8%
1/21 • Number of events 1 • Up to 5 years
|
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Cardiac disorders
Hypotension
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19.0%
4/21 • Number of events 4 • Up to 5 years
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Hepatobiliary disorders
Cholecystitis
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4.8%
1/21 • Number of events 1 • Up to 5 years
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Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils
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14.3%
3/21 • Number of events 3 • Up to 5 years
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Other adverse events
| Measure |
Treatment Plan
n=21 participants at risk
(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 and 8, 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 -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 (Ontak) 18 mcg/kg/day days 1- 5
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|---|---|
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Gastrointestinal disorders
Diarrhea
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9.5%
2/21 • Number of events 4 • Up to 5 years
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Respiratory, thoracic and mediastinal disorders
Pneumonitis/pulmonary infiltrates
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9.5%
2/21 • Number of events 2 • Up to 5 years
|
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Metabolism and nutrition disorders
Liver Function abnormalities
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33.3%
7/21 • Number of events 7 • Up to 5 years
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Additional Information
Lawrence Kaplan, MD
University of California, San Francisco
Phone: (415) 353-2661
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place