CHOEP + High Dose Therapy + Auto SCT for T-Cell Lymphoma
Study Details
Study Description
Brief Summary
The current standard of care for the frontline treatment of peripheral T-cell lymphomas (PTCL) is induction chemotherapy followed by autologous stem cell transplantation (ASCT). However, many patients are unable to get to ASCT or relapse after ASCT, with a poor prognosis. Recently, a novel ASCT conditioning regimen of gemcitabine, busulfan and melphalan (Gem/Bu/Mel) has been reported to lead to favorable outcomes in this disease. We therefore designed a frontline regimen of CHOEP induction followed by Gem/Bu/Mel ASCT, and report the results of a phase 2 study of this regimen in patients with PTCL.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Objectives:
Primary
- To estimate the proportion of patients alive and progression-free at 24 months after beginning induction therapy
Secondary
-
To estimate the response rate (complete remission (CR) and partial remission (PR)) after CHOEP x 6 and after Gem/Bu/Mel ASCT
-
To estimate overall survival (OS), progression-free survival (PFS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM)
-
To estimate the toxicity (grade 3 and above)
-
To estimate the rate of successful stem cell mobilization after CHOEP in responding patients
-
To estimate the proportion of patients who can successfully complete the entire treatment regimen
-
To estimate the time to engraftment of neutrophil and platelet engraftment after ASCT
-
To determine whether tumor DNA can be detected in peripheral blood of patients before therapy
-
To evaluate the changes and prognostic relevance in detectable tumor DNA in peripheral blood after induction chemotherapy (CHOEP) and after Gem/Bu/Mel ASCT
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CHOEP + High Dose Therapy + Auto SCT Patients received 6 cycles of induction chemotherapy: Cyclophosphamide, Doxorubicin, Vincristine, Etoposide and Prednisone (CHOEP) (5 if previously received 1 cycle of CHOP). CHOP was given at standard doses, with a dose of etoposide of 100 mg/m2 intravenously (IV) or 200 mg/m2 orally added on days 1-3 of each cycle. Patients who did not achieve a partial (PR) or complete (CR) remission at restaging after either 3 or 6 cycles were taken off study. Responders after 6 cycles had stem cell (SC) mobilization using filgrastim and plerixafor (if necessary) within 4 weeks of the end of induction. SC mobilization, harvesting, and reinfusion were performed per standard institutional protocol. A minimum collection of 2x106 CD34+ cells/kg was required to proceed to autologous stem cell transplant. Conditioning was comprised of gemcitabine 2700 mg/m2 on days -8 and -3, IV busulfan 105 mg/m2 days -8 to -5, and melphalan 60 mg/m2 given daily on days -3 and -2 (per MD Andersen protocol). |
Drug: Cyclophosphamide
Other Names:
Drug: Doxorubicin
Other Names:
Drug: Vincristine
Other Names:
Drug: Etoposide
Other Names:
Drug: Prednisone
Drug: Filgrastim
Other Names:
Drug: Plerixafor
Other Names:
Procedure: Stem Cell Collection
Other Names:
Drug: Palifermin
Other Names:
Drug: Gemcitabine
Other Names:
Drug: Busulfan
Other Names:
Drug: Melphalan
Procedure: Stem Cell Transplant
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 24-month Progression-Free Survival Rate [Disease was re-staged at cycles 3 and 6 during induction, at day 100 post-ASCT, and in long-term follow-up at months 12, 18, 24 and 36. All patients were evaluable up to month 24.]
24-month progression-free survival rate is defined as the proportion of patients remaining alive and progression-free at 24 months from start of induction therapy. Disease progression was assessed using a combination of CT scans and PET scans. Progression was categorized according to standard lymphoma response criteria, specifically the Revised Response Criteria (Cheson 2007).
Secondary Outcome Measures
- Induction Response [Disease was re-staged at cycles 3 and 6 during induction. Median duration of induction therapy in this study cohort was 6 cycles/18 weeks (range 2-6 cycles).]
Induction response is the defined as the proportion of patients who achieve complete remission (CR) or partial remission (PR) during 6 cycles of induction therapy. Response was assessed was using a combination of CT scans and PET scans. Partial and complete response were categorized according to standard lymphoma response criteria, specifically the Revised Response Criteria (Cheson 2007). Given the cycle length of 3 weeks, induction duration per protocol was 18 weeks.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Diagnosis of T-Cell lymphoma with mandatory pathologic review at Brigham and Women's Hospital or Massachusetts General Hospital
-
Measurable disease
-
Candidate for Autologous Stem Cell Transplant
Exclusion Criteria:
-
Prior anti-lymphoma chemotherapy (except steroids/radiotherapy for urgent palliation, one prior cycle of CHOP or up to 2 prior cycles of CHOEP)
-
Pregnant or breastfeeding
-
Alk-positive ACL
-
Significant neuropathy precluding vincristine administration
-
Known hypersensitivity to any of the agents used in the treatment
-
Uncontrolled intercurrent illness
-
Receiving other investigational agents
-
History of a different malignancy except if disease free for at least 5 years or have cervical cancer in situ or basal cell/squamous cell carcinoma of the skin
-
HIV positive on anti-retroviral therapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Brigham and Women's Hospital | Boston | Massachusetts | United States | 02215 |
| 2 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
Sponsors and Collaborators
- Dana-Farber Cancer Institute
- Massachusetts General Hospital
- Beth Israel Deaconess Medical Center
Investigators
- Principal Investigator: Philippe Armand, MD, Dana-Farber Cancer Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 12-388
Study Results
Participant Flow
| Recruitment Details | 5 patients were enrolled between July 2013 and January 2014. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | CHOEP + High Dose Therapy + Auto SCT |
|---|---|
| Arm/Group Description | Patients received 6 cycles of induction chemotherapy: Cyclophosphamide, Doxorubicin, Vincristine, Etoposide and Prednisone (CHOEP) (5 if previously received 1 cycle of CHOP). CHOP was given at standard doses, with a dose of etoposide of 100 mg/m2 intravenously (IV) or 200 mg/m2 orally added on days 1-3 of each cycle. Patients who did not achieve a partial (PR) or complete (CR) remission at restaging after either 3 or 6 cycles were taken off study. Responders after 6 cycles had stem cell (SC) mobilization using filgrastim and plerixafor (if necessary) within 4 weeks of the end of induction. SC mobilization, harvesting, and reinfusion were performed per standard institutional protocol. A minimum collection of 2x106 CD34+ cells/kg was required to proceed to autologous stem cell transplant. Conditioning was comprised of gemcitabine 2700 mg/m2 on days -8 and -3, IV busulfan 105 mg/m2 days -8 to -5, and melphalan 60 mg/m2 given daily on days -3 and -2 (per MD Andersen protocol). |
| Period Title: Overall Study | |
| STARTED | 5 |
| COMPLETED | 3 |
| NOT COMPLETED | 2 |
Baseline Characteristics
| Arm/Group Title | CHOEP + High Dose Therapy + Auto SCT |
|---|---|
| Arm/Group Description | Patients received 6 cycles of induction chemotherapy: Cyclophosphamide, Doxorubicin, Vincristine, Etoposide and Prednisone (CHOEP) (5 if previously received 1 cycle of CHOP). CHOP was given at standard doses, with a dose of etoposide of 100 mg/m2 intravenously (IV) or 200 mg/m2 orally added on days 1-3 of each cycle. Patients who did not achieve a partial (PR) or complete (CR) remission at restaging after either 3 or 6 cycles were taken off study. Responders after 6 cycles had stem cell (SC) mobilization using filgrastim and plerixafor (if necessary) within 4 weeks of the end of induction. SC mobilization, harvesting, and reinfusion were performed per standard institutional protocol. A minimum collection of 2x106 CD34+ cells/kg was required to proceed to autologous stem cell transplant. Conditioning was comprised of gemcitabine 2700 mg/m2 on days -8 and -3, IV busulfan 105 mg/m2 days -8 to -5, and melphalan 60 mg/m2 given daily on days -3 and -2 (per MD Andersen protocol). |
| Overall Participants | 5 |
| Age (years) [Mean (Full Range) ] | |
| Mean (Full Range) [years] |
55
|
| Sex: Female, Male (Count of Participants) | |
| Female |
2
40%
|
| Male |
3
60%
|
| Region of Enrollment (Count of Participants) | |
| United States |
5
100%
|
| Stage (Count of Participants) | |
| Stage I |
1
20%
|
| Stage II |
0
0%
|
| Stage III |
2
40%
|
| Stage IV |
2
40%
|
Outcome Measures
| Title | 24-month Progression-Free Survival Rate |
|---|---|
| Description | 24-month progression-free survival rate is defined as the proportion of patients remaining alive and progression-free at 24 months from start of induction therapy. Disease progression was assessed using a combination of CT scans and PET scans. Progression was categorized according to standard lymphoma response criteria, specifically the Revised Response Criteria (Cheson 2007). |
| Time Frame | Disease was re-staged at cycles 3 and 6 during induction, at day 100 post-ASCT, and in long-term follow-up at months 12, 18, 24 and 36. All patients were evaluable up to month 24. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis dataset is comprised all enrolled patients. |
| Arm/Group Title | CHOEP + High Dose Therapy + Auto SCT |
|---|---|
| Arm/Group Description | Patients received 6 cycles of induction chemotherapy: Cyclophosphamide, Doxorubicin, Vincristine, Etoposide and Prednisone (CHOEP) (5 if previously received 1 cycle of CHOP). CHOP was given at standard doses, with a dose of etoposide of 100 mg/m2 intravenously (IV) or 200 mg/m2 orally added on days 1-3 of each cycle. Patients who did not achieve a partial (PR) or complete (CR) remission at restaging after either 3 or 6 cycles were taken off study. Responders after 6 cycles had stem cell (SC) mobilization using filgrastim and plerixafor (if necessary) within 4 weeks of the end of induction. SC mobilization, harvesting, and reinfusion were performed per standard institutional protocol. A minimum collection of 2x106 CD34+ cells/kg was required to proceed to autologous stem cell transplant. Conditioning was comprised of gemcitabine 2700 mg/m2 on days -8 and -3, IV busulfan 105 mg/m2 days -8 to -5, and melphalan 60 mg/m2 given daily on days -3 and -2 (per MD Andersen protocol). |
| Measure Participants | 5 |
| Number (90% Confidence Interval) [proportion of patients] |
0.0
|
| Title | Induction Response |
|---|---|
| Description | Induction response is the defined as the proportion of patients who achieve complete remission (CR) or partial remission (PR) during 6 cycles of induction therapy. Response was assessed was using a combination of CT scans and PET scans. Partial and complete response were categorized according to standard lymphoma response criteria, specifically the Revised Response Criteria (Cheson 2007). Given the cycle length of 3 weeks, induction duration per protocol was 18 weeks. |
| Time Frame | Disease was re-staged at cycles 3 and 6 during induction. Median duration of induction therapy in this study cohort was 6 cycles/18 weeks (range 2-6 cycles). |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | CHOEP + High Dose Therapy + Auto SCT |
|---|---|
| Arm/Group Description | Patients received 6 cycles of induction chemotherapy: Cyclophosphamide, Doxorubicin, Vincristine, Etoposide and Prednisone (CHOEP) (5 if previously received 1 cycle of CHOP). CHOP was given at standard doses, with a dose of etoposide of 100 mg/m2 intravenously (IV) or 200 mg/m2 orally added on days 1-3 of each cycle. Patients who did not achieve a partial (PR) or complete (CR) remission at restaging after either 3 or 6 cycles were taken off study. Responders after 6 cycles had stem cell (SC) mobilization using filgrastim and plerixafor (if necessary) within 4 weeks of the end of induction. SC mobilization, harvesting, and reinfusion were performed per standard institutional protocol. A minimum collection of 2x106 CD34+ cells/kg was required to proceed to autologous stem cell transplant. Conditioning was comprised of gemcitabine 2700 mg/m2 on days -8 and -3, IV busulfan 105 mg/m2 days -8 to -5, and melphalan 60 mg/m2 given daily on days -3 and -2 (per MD Andersen protocol). |
| Measure Participants | 5 |
| Number (90% Confidence Interval) [proportion of patients] |
.60
|
Adverse Events
| Time Frame | Toxicity was assessed weekly during 6 cycles of induction (up to 18 weeks), within 0-3 days prior to day 1 of stem cell mobilization, day +30 post-ASCT. Median duration of induction therapy was 6 cycles/18 weeks (range 2-6 cycles). 3 patients continued to ASCT within 7 months of study enrollment. | |
|---|---|---|
| Adverse Event Reporting Description | Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4. No further data is available to specify classification of other beyond the general term. | |
| Arm/Group Title | CHOEP + High Dose Therapy + Auto SCT | |
| Arm/Group Description | Patients received 6 cycles of induction chemotherapy: Cyclophosphamide, Doxorubicin, Vincristine, Etoposide and Prednisone (CHOEP) (5 if previously received 1 cycle of CHOP). CHOP was given at standard doses, with a dose of etoposide of 100 mg/m2 intravenously (IV) or 200 mg/m2 orally added on days 1-3 of each cycle. Patients who did not achieve a partial (PR) or complete (CR) remission at restaging after either 3 or 6 cycles were taken off study. Responders after 6 cycles had stem cell (SC) mobilization using filgrastim and plerixafor (if necessary) within 4 weeks of the end of induction. SC mobilization, harvesting, and reinfusion were performed per standard institutional protocol. A minimum collection of 2x106 CD34+ cells/kg was required to proceed to autologous stem cell transplant. Conditioning was comprised of gemcitabine 2700 mg/m2 on days -8 and -3, IV busulfan 105 mg/m2 days -8 to -5, and melphalan 60 mg/m2 given daily on days -3 and -2 (per MD Andersen protocol). | |
All Cause Mortality |
||
| CHOEP + High Dose Therapy + Auto SCT | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| CHOEP + High Dose Therapy + Auto SCT | ||
| Affected / at Risk (%) | # Events | |
| Total | 4/5 (80%) | |
| Blood and lymphatic system disorders | ||
| Anemia | 1/5 (20%) | |
| Febrile neutropenia | 2/5 (40%) | |
| Investigations | ||
| Lymphocyte count decreased | 1/5 (20%) | |
| Neutrophil count decreased | 2/5 (40%) | |
| Platelet count decreased | 1/5 (20%) | |
| White blood cell decreased | 2/5 (40%) | |
Other (Not Including Serious) Adverse Events |
||
| CHOEP + High Dose Therapy + Auto SCT | ||
| Affected / at Risk (%) | # Events | |
| Total | 5/5 (100%) | |
| Blood and lymphatic system disorders | ||
| Anemia | 1/5 (20%) | |
| Gastrointestinal disorders | ||
| Anal stenosis | 1/5 (20%) | |
| Diarrhea | 1/5 (20%) | |
| Nausea | 1/5 (20%) | |
| Vomiting | 2/5 (40%) | |
| General disorders | ||
| Chills | 1/5 (20%) | |
| Edema limbs | 1/5 (20%) | |
| Fatigue | 3/5 (60%) | |
| Fever | 1/5 (20%) | |
| Infections and infestations | ||
| Infections and infestations - Other | 1/5 (20%) | |
| Investigations | ||
| Neutrophil count decreased | 1/5 (20%) | |
| White blood cell decreased | 1/5 (20%) | |
| Musculoskeletal and connective tissue disorders | ||
| Generalized muscle weakness | 1/5 (20%) | |
| Musculoskeletal and connective tissue disorder - Other | 1/5 (20%) | |
| Nervous system disorders | ||
| Peripheral sensory neuropathy | 1/5 (20%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 1/5 (20%) | |
| Dyspnea | 1/5 (20%) | |
| Skin and subcutaneous tissue disorders | ||
| Skin and subcutaneous tissue disorders - Other | 1/5 (20%) | |
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 | Philippe Armand MD, PhD |
|---|---|
| Organization | Dana-Farber Cancer Institute |
| Phone | 617.632.2305 |
| Philippe_Armand@dfci.harvard.edu |
- 12-388