Multiple MyelomaPhase 3NCT00215943
Phase III Randomized Trial of Thalidomide/Dexamethasone Versus Vincristine+Adriamycin+Dexamethasone (VAD)
A Phase 3 study testing zoledronic acid, dexamethasone and thalidomide in people with Multiple Myeloma, run by H. Lee Moffitt Cancer Center and Research Institute at 5 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- zoledronic acid, dexamethasone and thalidomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 5 sitesin 2 countries
- Study dates
- Jun 2003to Aug 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States4 sites
Morton Plant Hospital
Clearwater, Florida, 33756
Watson Clinic
Lakeland, Florida, 33805
Fawcett Memorial Hospital
Port Charlotte, Florida, 33949
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612
About this study
Official title: Phase III Randomized Trial of Thalidomide/Dexamethasone vs VAD as Induction Chemotherapy for Newly Diagnosed Myeloma Patients and Evaluation of the Effects of Zoledronate on Chemotherapy Induced Apoptosis and Antigen Presentation.
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).
Read the detailed description
Patients Randomized to receive VAD (vincristine, adriamycin, dexamethasone): All patients received four cycles of VAD repeated every 4 weeks. Chemotherapy was administered by continuous IV Infusion for 96 hours: vincristine at a dose of 0.4 mg/day and doxorubicin at a dose of 9 mg/m^2/day. Patients were administered dexamethasone 40 mg by mouth (PO) on days 1 to 4, 9 to 12, and 17 to 20 of the initial two cycles. Dexamethasone was given only on days 1-4 of all subsequent cycles. Patients were randomized to receive zoledronic acid IV 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. Upon initiation of Zometa therapy, the following guidelines were applied: For patients with creatinine clearance >60 mL/min, the recommended dose remained at 4mg. For patients with reduced creatinine clearance, dosing was calculated to achieve the same area under curve (AUC) as in patients with creatinine clearance of 75 mL/min. Creatinine clearance was calculated using the Cockcroft-Gault formula.
- Conditions
- Multiple Myeloma
- Being tested
- zoledronic acid, dexamethasone, thalidomide, vincristine, adriamycin
- Keywords
- hematologic malignancy
- Medical subject headings
- Multiple Myeloma, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
zoledronic acidDrug
Also called Zometa®, Zoledronate
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.
dexamethasoneDrug
Also called Decadron, NSC-34521
As outlined in VAD Treatment arm and Thalidomide and Dexamethasone Treatment arm
thalidomideDrug
Also called Thalomid™
As outlined in Thalidomide and Dexamethasone Treatment arm
vincristineDrug
Also called Oncovin, NSC-67574
As outlined in VAD Treatment Arm
adriamycinDrug
Also called Doxorubicin, NSC-123127
As outlined in VAD Treatment arm
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: zoledronic acid; Drug: dexamethasone; Drug: thalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: End of Cycle 4 - 4 Months per Participant
Secondary outcomes (3)
Number of Participants With Adverse Events, by Group
Number of participants with toxicities of Thalidomide/Dexamethasone vs. VAD as induction regimens in newly diagnosed multiple myeloma (MM).
Measured: 4 Years, 7 Months
Number of Participants With Progression Free Survival (PFS), by Treatment Arm
Number of participants with PFS for thalidomide/Dexamethasone vs. VAD with respect to progression free survival in newly diagnosed MM. Progressive Disease (PD): (for patients not in CR) Requires one or more of the following; > 25% increase in the level of serum monoclonal paraprotein, which must also be an absolute increase of at least 5 g/L and confirmed on a repeat investigation.
> 25% increase in 24-hour urinary light chain excretion, which must also be an absolute increase of at least 200mg and confirmed on a repeat investigation.
>25% increase in plasma cells in a bone marrow aspirate, which also must be an absolute increase of at least 10%. Definite increase in the size of existing lytic lesions or plasmacytomas. Development of new bone lesions or plasmacytomas (except compression fractures). Development of hypercalcemia (corrected calcium > 11.5 mg/dL not attributable to other causes).
Measured: 4 Months
Overall Survival (OS), by Treatment Arm
Median OS for thalidomide/Dexamethasone participants vs. VAD participants. Months from On Study to Expired/Last Date Known Alive.
Investigators had planned to accrue 176 participants to calculate median overall survival.
Measured: Up to 10 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2005 (estimated)
- Study startJun 2003
- Primary completionAug 2012
- Study completionAug 2012
Why it stopped: Poor accrual, changes in management of newly diagnosed myeloma patients, new drugs/more effective regimens.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Melissa Alsina, MD, Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00215943
- Sponsor's protocol ID
- MCC-13043
- Other IDs
- CZOL446E
- Status last verified
- Aug 2013
- First submitted
- 15 Sep 2005
- Last updated
- 17 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Randomized Trial of Thalidomide/Dexamethasone vs VAD as Induction Chemotherapy for Newly Diagnosed Myeloma Patients and Evaluation of the Effects of Zoledronate on Chemotherapy Induced Apoptosis and Antigen Presentation.
- ClinicalTrials.gov ID
- NCT00215943
- Acronym / sponsor ID
- MCC-13043
- Conditions
- Multiple Myeloma
- Keywords
- hematologic malignancy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor accrual, changes in management of newly diagnosed myeloma patients, new drugs/more effective regimens.
- Enrolment
- 90 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Jun 2003
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 22 Sep 2005 (estimated)
- Results
- Posted 4 Mar 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Patients Randomized to receive VAD (vincristine, adriamycin, dexamethasone): All patients received four cycles of VAD repeated every 4 weeks. Chemotherapy was administered by continuous IV Infusion for 96 hours: vincristine at a dose of 0.4 mg/day and doxorubicin at a dose of 9 mg/m^2/day. Patients were administered dexamethasone 40 mg by mouth (PO) on days 1 to 4, 9 to 12, and 17 to 20 of the initial two cycles. Dexamethasone was given only on days 1-4 of all subsequent cycles. Patients were randomized to receive zoledronic acid IV 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. Upon initiation of Zometa therapy, the following guidelines were applied: For patients with creatinine clearance >60 mL/min, the recommended dose remained at 4mg. For patients with reduced creatinine clearance, dosing was calculated to achieve the same area under curve (AUC) as in patients with creatinine clearance of 75 mL/min. Creatinine clearance was calculated using the Cockcroft-Gault formula.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| VAD Treatment | Active comparator | Drug: zoledronic acid, Drug: vincristine, Drug: adriamycinVAD (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. |
| Thalidomide and Dexamethasone Treatment | Active comparator | Drug: zoledronic acid, Drug: dexamethasone, Drug: thalidomideThalidomide 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| zoledronic acidAlso: Zometa®, ZoledronatePatients 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. | Drug | Thalidomide and Dexamethasone Treatment, VAD Treatment |
| dexamethasoneAlso: Decadron, NSC-34521As outlined in VAD Treatment arm and Thalidomide and Dexamethasone Treatment arm | Drug | Thalidomide and Dexamethasone Treatment |
| thalidomideAlso: Thalomid™As outlined in Thalidomide and Dexamethasone Treatment arm | Drug | Thalidomide and Dexamethasone Treatment |
| vincristineAlso: Oncovin, NSC-67574As outlined in VAD Treatment Arm | Drug | VAD Treatment |
| adriamycinAlso: Doxorubicin, NSC-123127As outlined in VAD Treatment arm | Drug | VAD Treatment |
Primary outcome
Response Rates of VAD vs. Thalidomide/Dexamethasone
Time frame: End of Cycle 4 - 4 Months per Participant
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.
3 secondary outcomes
Number of Participants With Adverse Events, by Group
Time frame: 4 Years, 7 Months
Number of Participants With Progression Free Survival (PFS), by Treatment Arm
Time frame: 4 Months
Overall Survival (OS), by Treatment Arm
Time frame: Up to 10 Years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Melissa Alsina, MD principal investigator
H. Lee Moffitt Cancer Center and Research Institute
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing zoledronic acid, dexamethasone and thalidomide in people with Multiple Myeloma, run by H. Lee Moffitt Cancer Center and Research Institute at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Mar 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response Rates of VAD vs. Thalidomide/Dexamethasone (time frame: End of Cycle 4 - 4 Months per Participant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2014.