Phase III Randomized Trial of Thalidomide/Dexamethasone Versus Vincristine+Adriamycin+Dexamethasone (VAD)

NCT00215943 | Terminated Phase 3 Results DMC

• 2 other identifiers: MCC-13043CZOL446E
• Study Type: interventional
• Target: 90
• Locations: 2 countries
• Sites: 5

Brief Summary

Investigators planned to accrue 176 participants, to compare the response rate, overall response rate and survival of patients with multiple myeloma (MM) when randomized to two regimens (thalidomide+Dexamethasone versus Vincristine+Adriamycin+Dexamethasone). Investigators also planned to test if treatment with zoledronate immediately prior to chemotherapy results in an enhanced response to treatment (i.e. increase in complete response rates).

Conditions

Multiple Myeloma

Keywords

hematologic malignancy

Outcome Measures

Primary Outcomes (1)

• Response Rates of VAD vs. Thalidomide/Dexamethasone

  Blade (15) criteria for remission in multiple myeloma was used to assess response. Complete Response (CR)includes: Disappearance of the original monoclonal protein from the blood and urine on at least two determinations for a minimum of 6 weeks by immunofixation studies. Partial Response (PR) includes: At least a 50% reduction in the level of serum monoclonal protein for at least two determinations 6 weeks apart. Minimal Response (MR)includes: At least a 25% to 49% reduction in the level of serum monoclonal protein for at least 2 determinations 2 weeks apart.

  End of Cycle 4 - 4 Months per Participant

Secondary Outcomes (3)

• Number of Participants With Adverse Events, by Group

  4 Years, 7 Months

• Number of Participants With Progression Free Survival (PFS), by Treatment Arm

  4 Months

• Overall Survival (OS), by Treatment Arm

  Up to 10 Years

Study Arms (2)

VAD Treatment

ACTIVE COMPARATOR

VAD (vincristine, adriamycin, dexamethasone). Vincristine and adriamycin was administered by continuous infusion via a venous catheter for 96 hours every 28 days. Each 28 days is considered one "cycle" of therapy. Patients were to receive 4 to 6 cycles of therapy. Dexamethasone was taken in pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4. Patients were randomized to receive zoledronic acid IV on either Day 1 or 15 of each cycle.

Drug: zoledronic acid; Drug: vincristine; Drug: adriamycin

Thalidomide and Dexamethasone Treatment

ACTIVE COMPARATOR

Thalidomide was taken orally once every day in the evening for four to six months. The dexamethasone was taken in a pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4.

Drug: zoledronic acid; Drug: dexamethasone; Drug: thalidomide

Interventions

zoledronic acid DRUG

Patients were randomized to receive zoledronic acid I.V. on either Day 1 or 15 of each cycle. This schedule continued monthly as long as the patient remained on study. The dose was calculated based on the patients' monthly creatinine clearance.

Also known as: Zometa®, Zoledronate

Thalidomide and Dexamethasone Treatment; VAD Treatment

dexamethasone DRUG

As outlined in VAD Treatment arm and Thalidomide and Dexamethasone Treatment arm

Also known as: Decadron, NSC-34521

Thalidomide and Dexamethasone Treatment

thalidomide DRUG

As outlined in Thalidomide and Dexamethasone Treatment arm

Also known as: Thalomid™

Thalidomide and Dexamethasone Treatment

vincristine DRUG

As outlined in VAD Treatment Arm

Also known as: Oncovin, NSC-67574

VAD Treatment

adriamycin DRUG

As outlined in VAD Treatment arm

Also known as: Doxorubicin, NSC-123127

VAD Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have newly diagnosed MM confirmed by the presence of bone marrow plasmacytosis with \> 10 percent plasma cells, sheets of plasma cells, or biopsy-proven plasmacytoma. Patients must have Durie-Salmon Stage IIA-B or IIIA-B. Patients with non-secretory myeloma are eligible. (These patients will not be included in the analysis of response rates, but will be assessed for toxicity and survival).
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, 2, or 3
• ≥ 18 years of age.
• Signed informed consent form
• Expected survival of greater than 8 weeks
• Capable of swallowing study medication tablets
• Capable of following directions regarding taking study medication, or has a daily care provider who will be responsible for administering study medication.
• Patients will be eligible for study even if they lack socioeconomic access to autologous transplantation. (These patients will be identified prior to randomization so as not to confound study results).
• All patients (in the event that they are randomized to the thalidomide/dexamethasone arm) must agree to take part in the "System for Education and Prescribing Safety" (S.T.E.P.S.)™. They must sign a separate informed consent for this program.

You may not qualify if:

• Elevated direct bilirubin \> 2 mg/dl
• Serum alanine aminotransferase (ALT) or serum aspartate aminotransferase (AST) \> 2 times the upper limit of normal (ULN)
• Absolute neutrophil count (ANC) \<1000/mL, unless felt to be secondary to myeloma
• Ongoing radiation therapy, or radiation therapy within 3 weeks prior to first treatment, unless the acute side effects associated with such therapy are resolved.
• Prior treatment for multiple myeloma
• Prior bisphosphonate use is allowed but they must be discontinued before starting treatment.
• Concurrent uncontrolled serious infection
• Patients with peripheral (sensory) neuropathy, grade 3 or higher
• Life-threatening illness (unrelated to tumor)
• History of any other ACTIVE and INVASIVE cancer other than the present condition (except non-melanoma skin cancer), unless in complete remission and off of all therapy for that disease for a minimum of 3 years.
• Women of childbearing potential (unless utilizing birth control) or who are pregnant or nursing will be excluded from this study.
• Patients with comorbid conditions that would contraindicate the use of vincristine, doxorubicin, dexamethasone, thalidomide, or zoledronate.
• Plasma Cell Leukemia

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Novartis: collaborator

Study Sites (5)

Morton Plant Hospital

Clearwater, Florida, 33756, United States

Location

Watson Clinic

Lakeland, Florida, 33805, United States

Location

Fawcett Memorial Hospital

Port Charlotte, Florida, 33949, United States

Location

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

San Juan VA Hospital

San Juan, 00921, Puerto Rico

Location

MeSH Terms

Conditions

Multiple Myeloma; Hematologic Neoplasms

Interventions

Zoledronic Acid; Dexamethasone; Calcium Dobesilate; Thalidomide; Vincristine; Doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Aminoglycosides; Glycosides; Carbohydrates

Limitations and Caveats

Target accrual for planned analysis (176) was not met. Principal Investigator (PI) determined study must close due to changes in the management of newly diagnosed myeloma (emergence of new drugs, more effective regimens).

Results Point of Contact

• Title: Melissa Alsina, M.D.
• Organization: H. Lee Moffitt Cancer Center and Research Institute

melissa.alsina@moffitt.org

813-745-6886

Study Officials

• Melissa Alsina, MD

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2005
• First Posted: September 22, 2005
• Study Start: June 1, 2003
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: April 17, 2014
• Results First Posted: March 4, 2014

Record last verified: 2013-08

Locations

PR (1); US (4)