Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Closed 15 and over Other WU-99-0236 NCI-V00-1608, NCT00006220

Objectives

I.  Determine the maximum tolerated dose (MTD) and dose limiting toxicity of 
arsenic trioxide in patients with refractory hematologic malignancies.

II.  Determine the complete or partial response to arsenic trioxide at the MTD 
in these patients.

III.  Determine the response to and toxicity of arsenic trioxide when 
administered with tretinoin in these patients.

IV.  Determine the pharmacokinetics of arsenic trioxide with and without 
tretinoin in these patients.

V.  Determine the chronic toxicities of these treatment regimens in these 
patients.

Entry Criteria

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.

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)

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 

Expected Enrollment

Approximately 63-290 patients (3-40 treated in phase I; 10-155 treated in 
phase II (10-29 patients per diagnostic group); and 50-95 treated with arsenic 
trioxide and tretinoin) will be accrued for this study.

Outline

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.

Trial Contact Information

Trial Lead Organizations

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

Randy Brown, MD, Protocol chair		Ph: 314-454-8227; 800-600-3606 Email: rbrown@im.wustl.edu

Registry Information
Official Title		Arsenic Trioxide Alone or With ATRA (Vesanoid) for Resistant Hematologic Malignancy
Trial Start Date		2000-08-16
Registered in ClinicalTrials.gov		NCT00006220
Date Submitted to PDQ		2000-06-28
Information Last Verified		2007-07-12

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