Arsenic Trioxide, Ascorbic Acid, Dexamethasone, and Thalidomide in Treating Patients With Multiple Myeloma

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00112879
First received: June 2, 2005
Last updated: July 9, 2013
Last verified: December 2006
  Purpose

RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Thalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. Giving arsenic trioxide together with ascorbic acid, dexamethasone, and thalidomide may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving arsenic trioxide together with ascorbic acid, dexamethasone, and thalidomide work in treating patients with multiple myeloma.


Condition Intervention Phase
Stage I Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma
Refractory Plasma Cell Neoplasm
Drug: arsenic trioxide
Drug: ascorbic acid
Drug: dexamethasone
Drug: thalidomide
Procedure: anti-cytokine therapy
Procedure: antiangiogenesis therapy
Procedure: biological therapy
Procedure: chemotherapy
Procedure: drug resistance inhibition
Procedure: growth factor antagonist therapy
Procedure: non-specific immune-modulator therapy
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Phase II Study of Arsenic Trioxide, Ascorbic Acid, Dexamethasone, and Thalidomide in Patients With Previously Untreated High-Risk or Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Enrollment: 0
Detailed Description:

OBJECTIVES:

Primary

  • Determine the response rate in patients with previously untreated high-risk or relapsed or refractory multiple myeloma (MM) treated with arsenic trioxide, ascorbic acid, dexamethasone, and thalidomide.
  • Determine the safety of this regimen in these patients.

Secondary

  • Determine the duration of response, progression-free survival, and overall survival of patients with previously untreated high-risk MM treated with this regimen.

OUTLINE: This is an open-label study.

  • Induction therapy: Patients receive arsenic trioxide IV over 1-4 hours and ascorbic acid IV over 15-30 minutes on days 1-5 in week 1 and then twice weekly in weeks 2-12; oral dexamethasone on days 1-4, 11-14, 29-32, 39-42, 57-60, and 67-70 (weeks 1, 2, 5, 6, 9, and 10); and oral thalidomide once daily in weeks 1-12.
  • Consolidation therapy: Beginning 4 weeks after completion of induction therapy, patients receive arsenic trioxide and ascorbic acid as in induction therapy; oral dexamethasone on days 1-4, 29-32, and 57-60 (weeks 1, 5, and 9); and oral thalidomide once daily in weeks 1-12.
  • Maintenance therapy: Beginning 4 weeks after completion of consolidation therapy, patients receive arsenic trioxide IV over 1-4 hours and ascorbic acid IV over 15-30 minutes on days 1, 8, 15, and 22. Treatment with arsenic trioxide and ascorbic acid repeats every 90 days (every 12 weeks). Patients also receive oral dexamethasone on days 1-4. Treatment with dexamethasone repeats every 28 days. Patients receive oral thalidomide once daily. Maintenance therapy continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 4 weeks and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 33-68 patients (15-34 with previously untreated high-risk multiple myeloma [MM] and 18-34 with relapsed or refractory MM) will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of multiple myeloma (MM), meeting 1 of the following criteria:
  • Previously untreated disease with poor prognosis, meeting 1 of the following criteria:
  • Active disease with β2 microglobulin ≥ 5.5 mg/dL
  • Inactive disease with peripheral plasma cells OR chromosome 13 or 14 abnormalities by fluorescent in situ hybridization
  • Relapsed or refractory disease
  • Measurable disease by serum and urine M-protein and/or measurable plasmacytoma

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2* NOTE: *ECOG 3 allowed for patients with bone pain due to MM

Life expectancy

  • At least 3 months

Hematopoietic

  • Platelet count ≥ 75,000/mm^3 unless plasma cells > 50% in bone marrow
  • Any WBC allowed provided plasma cells > 50% in bone marrow

Hepatic

  • SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN)
  • Bilirubin ≤ 2.5 times ULN

Renal

  • Creatinine ≤ 6.0 mg/dL

Cardiovascular

  • Absolute QT interval ≤ 460 msec with potassium ≥ 4.0 mEq/L AND magnesium ≥ 1.8 mg/dL
  • No conduction defects
  • No unstable angina
  • No myocardial infarction within the past 6 months
  • No congestive heart failure
  • No New York Heart Association class II-IV heart disease
  • No other significant underlying cardiac dysfunction

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective double-method contraception for ≥ 4 weeks before, during, and for ≥ 4 weeks after completion of study therapy
  • No blood, ova, or sperm donation during study participation
  • No history of grand mal seizures except infantile febrile seizures
  • No pre-existing neurotoxicity or neuropathy ≥ grade 2
  • No uncontrolled diabetes mellitus
  • No active serious infection that cannot be controlled with antibiotics
  • No other malignancy within the past 5 years except curatively treated carcinoma in situ of the cervix or nonmelanoma skin cancer
  • No other condition that would preclude study compliance or follow up

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Prior thalidomide allowed (in patients with relapsed or refractory MM)
  • No prior thalidomide in combination with arsenic trioxide
  • Prior epoetin alfa allowed

Chemotherapy

  • See Biologic therapy
  • Prior arsenic trioxide allowed (for patients with relapsed or refractory MM)
  • No concurrent cytotoxic chemotherapy
  • No chemotherapy within 2 weeks after completion of study treatment

Endocrine therapy

  • Prior steroid therapy allowed (for patients with relapsed or refractory MM)

Radiotherapy

  • No concurrent broad-field radiotherapy

Surgery

  • Not specified

Other

  • Prior and concurrent bisphosphonates allowed
  • No other concurrent investigational agents
  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: NCT00112879

Locations
United States, Ohio
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
The Cleveland Clinic
Investigators
Study Chair: Mohamad A. Hussein, MD The Cleveland Clinic
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00112879     History of Changes
Other Study ID Numbers: CCF-IRB-7469, CDR0000428248, CCF-IRB-5241, CCF-CTI-T12016
Study First Received: June 2, 2005
Last Updated: July 9, 2013
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Arsenic trioxide
Ascorbic Acid
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Mitogens
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents

ClinicalTrials.gov processed this record on October 23, 2014