Arsenic Trioxide With or Without Tretinoin in Treating Patients With Hematologic Cancer That Has Not Responded to Previous Therapy

February 4, 2013 updated by: Washington University School of Medicine

Arsenic Trioxide Alone or With ATRA (Vesanoid) for Resistant Hematologic Malignancy

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Tretinoin may help hematologic cancer cells develop into normal white blood cells.

PURPOSE: Phase I/II trial to study the effectiveness of arsenic trioxide with or without tretinoin in treating patients who have hematologic cancer that has not responded to previous therapy.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This is a dose escalation and efficacy study of arsenic trioxide. In the efficacy study, patients are stratified according to diagnosis (acute myelogenous leukemia vs acute lymphocytic leukemia vs myelodysplastic syndrome vs multiple myeloma vs non-Hodgkin's lymphoma and Hodgkin's disease). Phase I: Patients receive arsenic trioxide IV over 2 hours daily for 28 days. Treatment repeats every 42-59 days in the absence of disease progression or unacceptable toxicity. Patients who achieve complete remission (CR) or partial remission (PR) receive up to 4 courses. Patients who fail to achieve CR or PR or who experience disease progression may receive arsenic trioxide and tretinoin daily for 28 days every 42-59 days for up to 7 courses. Patients who fail to achieve CR or PR or experience disease progression with arsenic trioxide and tretinoin are removed from study. Cohorts of 3-6 patients receive escalating doses of arsenic trioxide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities. Phase II: Patients receive the MTD of arsenic trioxide as in phase I for up to 7 courses. Patients who fail to achieve CR or PR after 3 courses or experience disease progression are either taken off study or treated with arsenic trioxide and tretinoin as in phase I. Patients are followed monthly for 6 months, and then every 3 months for 18 months.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University Barnard Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS: Patients with any of the following diagnoses: Acute lymphocytic leukemia OR acute myeloid leukemia Failed to achieve complete remission (CR) with induction chemotherapy OR Relapsed within one year of initial CR OR Relapsed after autologous or allogeneic transplant OR Any subsequent relapse OR Refractory following relapse CR2 or more (phase I only) Blastic phase chronic myelogenous leukemia Prior therapy allowed Myelodysplastic syndrome, including the following: Refractory anemia with excess blasts (RAEB) OR RAEB in transformation (high intermediate or high risk only) Relapsed after transplant CR2 or more (phase I only) Non-Hodgkin's lymphoma OR Hodgkin's disease Newly diagnosed or in first relapse and failed to achieve CR or partial remission after induction or salvage chemotherapy OR Second or later relapse OR Relapsed after transplant No disease that can be encompassed in a standard radiation port No asymptomatic, minimally symptomatic, or low grade lymphoma Multiple myeloma Symptomatic, progressive, or recurrent disease after treatment with alkylating agents, high dose corticosteroids, or anthracyclines OR Relapsed following transplant Not eligible for autologous or allogeneic transplant A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS: Age: 15 and over Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 500/mm3* Platelet count at least 50,000/mm3* *Unless caused by marrow infiltration by tumor No congenital bleeding disorder Hepatic: Bilirubin less than 2 times upper limit of normal (ULN) SGOT less than 3 times ULN Renal: Creatinine clearance greater than 25 mL/min Cardiovascular: No myocardial infarction, stroke, or unstable angina within the past 12 months No uncompensated congestive heart failure Left ventricular ejection fraction at least 40% Other: No active infection HIV negative HTLV I/II negative Not pregnant Fertile patients must use effective contraception during and for 2 years following study

PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics Chemotherapy: See Disease Characteristics Prior hydroxyurea allowed Endocrine therapy: See Disease Characteristics Radiotherapy: See Disease Characteristics Surgery: Not specified Other: At least 3 weeks since prior antileukemic therapy (except leukapheresis)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase I
Starting dose of arsenic trioxide of 0.15 mg/kg/day
Drug: arsenic trioxide
Experimental: Phase II
MTD of arsenic trioxide
Drug: arsenic trioxide
Experimental: Treatment Failure
Arsenic trioxide and tretinoin
Drug: arsenic trioxide
Drug: tretinoin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT)
Time Frame: 28 days
28 days
Likelihood of complete (CR) or partial (PR) response following therapy
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Explore the pharmacokinetics of arsenic trioxide alone and in combination with ATRA
Evaluate acute and chronic toxicities of arsenic trioxide alone and in combination with ATRA.
Determine the effects of arsenic trioxide alone and combined with ATRA on bcl-2, pml, and class I antigen expression and on apoptosis. Determine the effects of arsenic trioxide on T and B cell number and function
Only when patients are circulating tumor cells.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Randy A. Brown, MD, Washington University Siteman Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 1999

Primary Completion (Actual)

November 1, 2000

Study Completion (Actual)

February 1, 2002

Study Registration Dates

First Submitted

September 11, 2000

First Submitted That Met QC Criteria

May 19, 2004

First Posted (Estimate)

May 20, 2004

Study Record Updates

Last Update Posted (Estimate)

February 6, 2013

Last Update Submitted That Met QC Criteria

February 4, 2013

Last Verified

February 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000068108
  • WU-99-0236
  • NCI-V00-1608

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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