Infections

All Conditions

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Immune System Diseases

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Leukemia, T-Cell

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Leukemia-Lymphoma, Adult T-Cell

Lymphoma

Leukemia, Lymphoid

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Adult T-cell Leukemia/lymphoma

Human T-cell Leukemia Virus Type 1

Leukemia, T-cell, Chronic

Lymphosarcoma

Anti-Infective Agents

All Drugs and Chemicals

Raltegravir Potassium

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Integrase Inhibitors

HIV Integrase Inhibitors

Enzyme Inhibitors

Raltegravir

Lee Ratner, MD PhD

This is a study of the effect of raltegravir on human T-cell leukemia virus type 1 (HTLV-1) viral load in asymptomatic patients. The study will enroll 14 subjects for a period of 2 months of treatment and 1 month of followup. The study will assess the effect of raltegravir on virus load in peripheral blood lymphocytes, level of virus gene expression, and sites of viral integration.

About 5% of HTLV-1 infected individuals develop lymphoma or myelopathy. High levels of virus replication are predictive of disease development. HTLV-1 exhibits lower levels of variation than HIV-1, suggesting that drug resistance is less likely to occur. Raltegravir was shown to inhibit HTLV-1 integration and replication in culture using concentrations achievable with the approved dose used in HIV-1 infected patients. Currently, no treatment is recommended for asymptomatic infected individuals.

Trial to Assess Effect of Raltegravir on HTLV-1 Proviral Load

Phase II Trial to Assess Effect of Raltegravir on HTLV-1 Proviral Load

Measured by DNA PCR from peripheral blood mononuclear cell DNA at days 0, 1, 8, 15, 29, 43, and 56.

Measured by real time PCR with DNA from sorted peripheral blood mononuclear cell DNA at days 1, 8, 15, 29, 43, and 56.

1. Number of LTR circles measure by real time PCR on peripheral blood mononculear cell DNA at days 0, 1, 8, 15, 29, 43, and 56
2. Level of Proviral RNA Expression in PBMCs measured by real time RT PCR on peripheral blood mononculear cell RNA at days 0, 1, 8, 15, 29, 43, and 56

Measured by automated sequence analysis of PCR amplified viral DNA obtained at days 0, 1, 8, 15, 29, 43, and 56

Measured by automated DNA analysis of oligonucleotide linked PCR amplified DNA from peripheral blood mononuclear cell DNA obtianed at days 0, 1, 8, 15, 29, 43,and 56

Assessed by physical exam, CBC, and serum chemistries on days 29 and 57 and

Merck Sharp & Dohme LLC

Washington University School of Medicine

Antineoplastic Agents

Antirheumatic Agents

Anti-Inflammatory Agents

Etoposide

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Prednisone

Vincristine

Bortezomib

Etoposide phosphate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Tubulin Modulators

Antimitotic Agents

Bortezomib 1.0 mg/m2 intravenous (IV) Days 1-4

Etoposide 50 mg/m2/d 96 hour continuous intravenous infusion (CIVI) on Days 1-4

Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4

Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4

Prednisone 60 mg/m2/d PO on Days 1-5

Cyclophosphamide 375 mg/m2 IV on Day 5

Raltegravir 400 mg PO twice per day (BID) every day starting with cycle 2 therapy for the entire duration of the cycle.

Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.

Lee Ratner, M.D., Ph.D.

The rationale of the current study is to explore the use of combination chemotherapy together with antiretroviral agents in order to determine the efficacy and toxicity of this approach, while also examining markers of virus replication and expression, and tumor cell proliferation to gain understanding of the biological basis of this malignancy and to identify predictors of response.

Primary Endpoint:

- To determine the tolerability and efficacy (response rate) of dose adjusted bortezomib-EPOCH (DA B-EPOCH) chemotherapy combined with Raltegravir in patients with HTLV-1 associated leukemia/lymphoma (ATLL).

Secondary Endpoints:

* To evaluate the effects of DA B-EPOCH chemotherapy combined with Raltegravir on HTLV-1 DNA and RNA load, HTLV-1 integrase gene sequence, and HTLV-1 integration sites. To determine if relapsed or progressive disease is a result of renewed virus replication.
* To evaluate the relation of NFκB gene expression profile on response to DA B-EPOCH chemotherapy combined with Raltegravir.

EPOCH Chemotherapy and Bortezomib for Associated T-Cell Leukemia Lymphoma

Phase I/II Trial of Dose-Adjusted EPOCH Chemotherapy With Bortezomib Combined With Integrase Inhibitor Therapy for HTLV-1 Associated T-Cell Leukemia Lymphoma

The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for all toxicity reporting.

-The response definitions used for this study are the 2007 Cheson criteria.

-The progression definitions used for this study are from the 2007 Cheson criteria.

Standard error represents the standard error of the fold expression of protein coding transcripts for each gene indicated.

Bortezomib 1.0 mg/m2 IV Days 1-4

Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4

Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4

Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4

Prednisone 60 mg/m2/d PO on Days 1-5

Cyclophosphamide 375 mg/m2 IV on Day 5

Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle.

Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.

EPOCH Chemotherapy & Bortezomib

Acute ATLL

Lymphoma ATLL

Total

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Antigua

Dominican Republic

Haiti

Jamaica

Virgin Islands

Bahamas

Birthplace

Fatigue

Vomiting

Spontaneous bacterial peritonitis

Abdominal distension

Hemoglobin

Leukocytes (WBC)

Lymphopenia

Neutrophils

Platelets

Infection without neutropenia

Infection with neutropenia

Omaya port infection

IV port infection

Sepsis

Neutropenic fever

Hypoglycemia

Hyperglycemia

Magnesium

Hypokalemia

Hypertriglyceridemia

Confusion

Headache

Encephalitis

Abdominal pain

Cough

Dyspnea

Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events

Progressive Disease

Stable disease

Partial response

Complete response

Efficacy of Treatment as Measured by Best Overall Response

Best response of complete response

Best response of partial response

Best response of stable disease

All participants

12 out of the 18 participants had a complete or partial response.

Time to Progression

Baseline

Study completion

Patients who had a complete or partial response to treatment

Responders

Patients who had stable or progressive disease after treatment.

Non-responders

Effects of on HTLV-1 DNA After Treatment as Measured by Proviral Loads

CADMI

CD25

CD45

Patient A (Responder) Pre-Therapy

Patient A (Responder) Post-Therapy

Patient B (Responder) Pre-Therapy

Patient B (Responder) Post-Therapy

Patient C (Non-responder) Pre-Therapy

Patient C (Non-responder) Post-Therapy

Patient D (Non-responder) Pre-Therapy

Patient D (Non-responder) Post-Therapy

Average RPKM values normalized to Patient A before therapy.

Relation of NFκB Gene Expression Profile on Response

Effects of HTLV-1 RNA Load After Treatment as Measured by Hbz Messenger RNA

Effects of HTLV-1 Integrase Gene Sequence After Treatment as Measured by Nucleotide Divergence

Effects of HTLV-1 Integration Sites After Treatment

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial to Assess Effect of Raltegravir on HTLV-1 Proviral Load	NCT01620736	Human T-cell Le...	Raltegravir	18 Years -	Washington University School of Medicine
Trial to Assess Effect of Raltegravir on HTLV-1 Proviral Load	NCT01620736	Human T-cell Le...	Raltegravir	18 Years -	Washington University School of Medicine
EPOCH Chemotherapy and Bortezomib for Associated T-Cell Leukemia Lymphoma	NCT01000285	Leukemia-Lympho...	Bortezomib Etoposide Vincristine Doxorubicin Prednisone Cyclophosphamid... Raltegravir	18 Years -	Washington University School of Medicine

Spots Global Cancer Trial Database for raltegravir

Every month we try and update this database with for raltegravir cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for raltegravir

Every month we try and update this database with for raltegravir cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for raltegravir cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.