CHOEP + High Dose Therapy + Auto SCT for T-Cell Lymphoma

NCT01746173 | Terminated Phase 2 Results DMC

• 1 other identifier: 12-388
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

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.

Conditions

T-cell Non-Hodgkin Lymphoma

Keywords

T Cell lymphoma

Outcome Measures

Primary Outcomes (1)

• 24-month Progression-Free Survival Rate

  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).

  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.

Secondary Outcomes (1)

• 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).

Study Arms (1)

CHOEP + High Dose Therapy + Auto SCT

EXPERIMENTAL

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; Drug: Doxorubicin; Drug: Vincristine; Drug: Etoposide; Drug: Prednisone; Drug: Filgrastim; Drug: Plerixafor; Procedure: Stem Cell Collection; Drug: Palifermin; Drug: Gemcitabine; Drug: Busulfan; Drug: Melphalan; Procedure: Stem Cell Transplant

Interventions

Cyclophosphamide DRUG

Also known as: cytoxan

CHOEP + High Dose Therapy + Auto SCT

Doxorubicin DRUG

Also known as: adriamycin

CHOEP + High Dose Therapy + Auto SCT

Vincristine DRUG

Also known as: oncovin

CHOEP + High Dose Therapy + Auto SCT

Etoposide DRUG

Also known as: Etopophos, Toposar, Etoposide phosphate

CHOEP + High Dose Therapy + Auto SCT

Prednisone DRUG

CHOEP + High Dose Therapy + Auto SCT

Filgrastim DRUG

Also known as: neupogen, G-CSF

CHOEP + High Dose Therapy + Auto SCT

Plerixafor DRUG

Also known as: mozobil

CHOEP + High Dose Therapy + Auto SCT

Stem Cell Collection PROCEDURE

Also known as: Leukapheresis

CHOEP + High Dose Therapy + Auto SCT

Palifermin DRUG

Also known as: KGF, kepivance

CHOEP + High Dose Therapy + Auto SCT

Gemcitabine DRUG

Also known as: gemzar

CHOEP + High Dose Therapy + Auto SCT

Busulfan DRUG

Also known as: busulfex

CHOEP + High Dose Therapy + Auto SCT

Melphalan DRUG

CHOEP + High Dose Therapy + Auto SCT

Stem Cell Transplant PROCEDURE

Also known as: Stem Cell Infusion

CHOEP + High Dose Therapy + Auto SCT

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Massachusetts General Hospital: collaborator
• Beth Israel Deaconess Medical Center: collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Lymphoma, T-Cell

Interventions

Cyclophosphamide; Doxorubicin; Vincristine; Etoposide; etoposide phosphate; Prednisone; Filgrastim; Granulocyte Colony-Stimulating Factor; plerixafor; Leukapheresis; Fibroblast Growth Factor 7; Gemcitabine; Busulfan; Melphalan; Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Fibroblast Growth Factors; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Cell Transplantation; Cell- and Tissue-Based Therapy; Transplantation; Surgical Procedures, Operative

Limitations and Caveats

The trial closed early due to poor accrual. The small sample size precludes definitive conclusions.

Results Point of Contact

• Title: Philippe Armand MD, PhD
• Organization: Dana-Farber Cancer Institute

Philippe_Armand@dfci.harvard.edu

617.632.2305

Study Officials

• Philippe Armand, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 4, 2012
• First Posted: December 10, 2012
• Study Start: July 1, 2013
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: January 30, 2023
• Results First Posted: January 11, 2017

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)