Brief Summary

Studies conducted at the National Cancer Institute suggest that certain chemotherapy drugs may be more effective if given by continuous infusion into the vein rather than by the standard method of rapid intravenous injection. One such combination of six chemotherapy drugs, known as Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, Rituximab (EPOCH-R), has had a high degree of effectiveness in people with certain kinds of cancer. Recent evidence also indicates that the effects of chemotherapy may be improved by combining the treatment with monoclonal antibodies, which are purified proteins that are specially made to attach to foreign substances such as cancer cells. This protocol is specifically for adults with the types of cancer known as T-cell and Naturel Killer (NK)-cell lymphomas, who have never received chemotherapy previously. The additional monoclonal antibody in the study, called siplizumab, has been manufactured to attach to the cluster of differentiation 2 (CD2) protein contained in these types of tumors. Study volunteers will need to undergo an initial period of evaluation that may take up to 3 weeks and may be done on an outpatient basis. Evaluation may include some or all of the following tests: blood and urine tests, tests of lung and heart function, lumbar punctures to take samples of cerebrospinal fluid, magnetic resonance imaging (MRI) or computerized tomography (CT) scans, full-body positron emission tomography (PET) scans, bone marrow biopsies, and biopsies of suspected tumor areas. During the study, patients will receive EPOCH-R chemotherapy, which includes the following drugs: etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab. The additional drug, siplizumab, will be given by IV infusion on the first day of treatment over several hours. When the siplizumab intravenous (IV) infusion is complete, the drugs doxorubicin, etoposide, and vincristine will each be given by continuous IV infusion over the next 4 days (that is, continuously for a total of 96 hours). When this infusion is completed, the drugs rituximab and cyclophosphamide will be given by IV infusion over several hours on Day 5. Prednisone will be given by mouth twice each day for 5 days. Patients may be given other drugs to treat the side effects of chemotherapy and to prevent possible infections. The siplizumab-EPOCH-R therapy will be repeated every 21 days, which is known as a cycle of therapy, for a total of 6 cycles. Following the fourth and sixth treatment cycles (approximately weeks 12 and 18) of siplizumab-EPOCH-R, study researchers will perform blood tests and CT/MRI scans on all patients to assess their response to the treatment.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at below P25 for phase_1

Timeline

Completed

Started Jan 2009

Longer than P75 for phase_1

Geographic Reach

1 country

1 active site

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

11.8 years study duration

Study Start

First participant enrolled

January 13, 2009

Completed

2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2011

Completed

6 months until next milestone

First Submitted

Initial submission to the registry

September 30, 2011

Completed

3 days until next milestone

First Posted

Study publicly available on registry

October 3, 2011

Completed

8.9 years until next milestone

Results Posted

Study results publicly available

August 18, 2020

Completed

2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 22, 2020

Completed

Last Updated

November 3, 2021

Status Verified

October 1, 2021

Enrollment Period

2.2 years

First QC Date

September 30, 2011

Results QC Date

May 12, 2020

Last Update Submit

October 28, 2021

Conditions

T-Cell Peripheral Lymphoma Gamma Delta Hepatosplenic T-Cell Lymphoma Subcutaneous Panniculitis-Like T-Cell Lymphoma NK T-Cell Lymphoma

Keywords

CD2 PositiveToxicityEBV LymphomaChemotherapy NaiveMaximum Tolerated DoseLymphomaT-Cell LymphomaNK T-Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

Number of Participants With Serious and Non-serious Adverse Events
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Date treatment consent signed until 30 days after removal from study treatment or until off study, whichever comes first, approximately 22 weeks.
Maximum Tolerated Dose (MTD) of Siplizumab
A classic 3+3 dose-escalation design was used to assess the MTD of siplizumab in combination with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (EPOCH-R). If 2 of 6 patients experienced a dose-limiting toxicity (DLT) at a particular dose level, the MTD has been exceeded. The preceding dose level will be the MTD, provided 6 patients have been entered at this level and no more than one has experienced a DLT. DLTs for siplizumab was defined as infusional grade 3 non-hematologic toxicity lasting longer than 6 hours after the infusion, any grade 4 non-hematologic toxicity, or the development of an Epstein Barr Virus (EBV)-related lymphoproliferative disorder (LPD). Expected toxicities of dose-adjusted EPOCH-R and grade 3 laboratory adverse events (AEs) were not considered to be DLTs.
First 30 days after treatment initiation.

Secondary Outcomes (3)

Number of Participants With a Response to Therapy
Response assessments were performed after the fourth and sixth cycle of therapy, at therapy completion, and every 3 months for year 1, four months for year 2, 6 months for years 3-5, and annually thereafter, up to 5 years.
Overall Progression Free Survival (PFS)
On-study date until date of progression or last follow up, approximately 7 months.
Overall Survival (OS)
On study date until date of death or last follow up, approximately 12 months.

Other Outcomes (1)

Number of Dose-Limiting Toxicities (DLT)
First 30 days after treatment initiation.

Study Arms (1)

siplizumab + EPOCH (combo chemo) + rituximab

EXPERIMENTAL

siplizumab will be given with EPOCH (combo chemo) and rituximab every 21 days

Biological: RituximabDrug: EtoposideBiological: SiplizumabDrug: PrednisoneDrug: VincristineDrug: CyclophosphamideDrug: Doxorubicin

Interventions

RituximabBIOLOGICAL

Rituximab will be given with siplizumab and etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin every 21 days

Also known as: Rituxan