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

This study has been terminated.
(Study drug became commercially available.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00006220
First received: September 11, 2000
Last updated: February 4, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Drug: arsenic trioxide
Drug: tretinoin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: Arsenic Trioxide Alone or With ATRA (Vesanoid) for Resistant Hematologic Malignancy

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Likelihood of complete (CR) or partial (PR) response following therapy [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Explore the pharmacokinetics of arsenic trioxide alone and in combination with ATRA [ Designated as safety issue: No ]
  • Evaluate acute and chronic toxicities of arsenic trioxide alone and in combination with ATRA. [ Designated as safety issue: Yes ]
  • 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 [ Designated as safety issue: No ]
    Only when patients are circulating tumor cells.


Enrollment: 5
Study Start Date: June 1999
Study Completion Date: February 2002
Primary Completion Date: November 2000 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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)

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006220

Locations
United States, Missouri
Washington University Barnard Cancer Center
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Study Chair: Randy A. Brown, MD Washington University Siteman Cancer Center
  More Information

No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00006220     History of Changes
Other Study ID Numbers: CDR0000068108, WU-99-0236, NCI-V00-1608
Study First Received: September 11, 2000
Last Updated: February 4, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Washington University School of Medicine:
stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
recurrent adult Hodgkin lymphoma
refractory multiple myeloma
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
stage III grade 3 follicular lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III adult Burkitt lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV adult Burkitt lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Myelodysplastic Syndromes
Preleukemia
Lymphoma
Leukemia
Syndrome
Plasmacytoma
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Precancerous Conditions
Lymphatic Diseases
Disease
Pathologic Processes
Arsenic trioxide
Tretinoin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014