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

Phase 1/Phase 2
18 Years
Open (Enrolling)
Leukemia-Lymphoma, Adult T-Cell

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Trial Information

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

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.

Inclusion Criteria:

- Histologically or cytologically documented ATLL. Patients with previously untreated
or treated ATLL are eligible.

- Tumors must be CD3 positive (>50% cells express CD3).

- Documented HTLV-1 infection: documentation may be serologic assay (ELISA, Western
blot) and confirmed to be HTLV-1 rather than HTLV-2 by differential Western blot
(e.g. Genelabs Diagnostics HTLV Blot 2.4) or PCR.

- Measurable disease must be present. These nodes or masses should be selected
according to all of the following: they should be clearly measurable in at least two
perpendicular dimensions; if possible they should be from disparate regions of the
body; and they should include mediastinal and retroperitoneal areas of disease
whenever these sites are involved.

- All stages are eligible.

- Adequate hematologic function within 14 days before enrollment: ANC>1000 cells/mm3,
platelet count>75,000 cells/mm3 unless cytopenias are secondary to ATLL. All
patients must be off hematologic growth factors for at least 24 hrs.

- Adequate hepatic function, transaminase <3 times the upper limit of normal unless due
to hepatic involvement by tumor; total bilirubin ≤1.5 times the upper limit of normal

- Creatinine<2.0 unless due to lymphoma.

- KPS at least 50

- Age at least 18. -Voluntary written informed consent before performance of any study-
related procedure not part of normal medical care, with the understanding that
consent may be withdrawn by the subject at any time without prejudice to future
medical care.

- Female patients of child bearing potential must have a negative pregnancy test within
72 hrs of initiation of therapy. Female patients are either post-menopausal or
surgically sterilized or willing to use two acceptable methods of birth control
(i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide,
condom with spermicide, or abstinence) during the study. Male patients must agree to
use two acceptable methods for contraception for the duration of the study. Women
must avoid pregnancy and men avoid fathering children while in the study.

- HIV positive patients are eligible if they are receiving at least two other active
anti-HIV therapies other than zidovudine or atazanavir.

- Patients with active HBV infection are eligible if they are receiving effective
anti-HBV therapy.

- Inclusion of Women and Minorities: Both men and women and members of all races and
ethnic groups are eligible for this trial.

Exclusion Criteria:

- Acute active infection requiring acute therapy. Chronic therapy with potentially
myelosuppressive agents is allowed provided that entry hematologic criteria are met.

- Diagnosed or treated for another malignancy within 3 years of enrollment, with the
exception of complete resection of basal cell carcinoma or squamous cell carcinoma of
the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.

- Women who are pregnant or breastfeeding. Confirmation that the subject is not
pregnant must be established by a negative serum B-human chorionic gonadotropin
(B-hCG) pregnancy test result obtained during screening. Pregnancy testing is not
required for post-menopausal or surgically sterilized women.

- Patient has ≥Grade 2 peripheral neuropathy

- Myocardial infarction within 6 months prior to enrollment or has New York Heart
Association (NYHA) Class III or IV heart failure (see Appendix VI), uncontrolled
angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence
of acute ischemia or active conduction system abnormalities. Prior to study entry,
any ECG abnormality at Screening has to be documented by the investigator as not
medically relevant.

- Patient has hypersensitivity to bortezomib, boron or mannitol.

- Patient has received other investigational drugs with 14 days before enrollment

- Serious medical or psychiatric illness likely to interfere with participation in this
clinical study.

- 1.5x ULN total bilirubin

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the tolerability and efficacy of dose adjusted bortezomib-EPOCH (DA B-EPOCH) chemotherapy combined with Raltegravir in ATLL patients

Outcome Description:

A sequential probability ratio test will be used to monitor the frequency of patients who fail to complete 2 cycles of chemo-antiviral therapy due to toxicity.

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

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

Investigator Role:

Principal Investigator

Investigator Affiliation:

Washington University School of Medicine


United States: Food and Drug Administration

Study ID:

09-1758 / 201108212



Start Date:

September 2010

Completion Date:

April 2018

Related Keywords:

  • Leukemia-Lymphoma, Adult T-Cell
  • Leukemia
  • Leukemia, T-Cell
  • Leukemia-Lymphoma, Adult T-Cell
  • Lymphoma



Johns Hopkins University Baltimore, Maryland  21205
Memorial Sloan Kettering Cancer Center New York, New York  10021
Washington University School of Medicine Saint Louis, Missouri  63110
Emory University School of Medicine Atlanta, Georgia  30322
Montefiore Medical Center Bronx, New York  10467-2490
University of Miami Hospital/Sylvester Miami, Florida  33136
Columbia University, College of Physicians and Surgeons New York, New York  10032