Arsenic Trioxide With or Without Tretinoin in Treating Patients With Hematologic Cancer That Has Not Responded to Previous Therapy
Information source: Washington University School of Medicine
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes
Intervention: arsenic trioxide (Drug); tretinoin (Drug)
Phase: Phase 1/Phase 2
Status: Terminated
Sponsored by: Washington University School of Medicine Official(s) and/or principal investigator(s): Randy A. Brown, MD, Study Chair, Affiliation: Washington University Siteman Cancer Center
Summary
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.
Clinical Details
Official title: Arsenic Trioxide Alone or With ATRA (Vesanoid) for Resistant Hematologic Malignancy
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Primary Purpose: Treatment
Primary outcome: Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT)Likelihood of complete (CR) or partial (PR) response following therapy
Secondary outcome: Explore the pharmacokinetics of arsenic trioxide alone and in combination with ATRAEvaluate 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
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
Minimum age: 15 Years.
Maximum age: N/A.
Gender(s): Both.
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)
Locations and Contacts
Washington University Barnard Cancer Center, Saint Louis, Missouri 63110, United States
Additional Information
Starting date: June 1999
Last updated: February 4, 2013
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