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


Phase 1/Phase 2
15 Years
N/A
Not Enrolling
Both
Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes

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Trial Information

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


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.

Inclusion 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)

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT)

Outcome Time Frame:

28 days

Safety Issue:

Yes

Principal Investigator

Randy A. Brown, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Washington University Siteman Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000068108

NCT ID:

NCT00006220

Start Date:

June 1999

Completion Date:

February 2002

Related Keywords:

  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • 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
  • recurrent adult Burkitt lymphoma
  • previously treated myelodysplastic syndromes
  • stage III mantle cell lymphoma
  • stage IV mantle cell lymphoma
  • recurrent mantle cell lymphoma
  • childhood myelodysplastic syndromes
  • Neoplasms
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Lymphoma, Large-Cell, Immunoblastic

Name

Location

Washington University Barnard Cancer CenterSaint Louis, Missouri  63110