Multiple MyelomaPhase 1/2Thal/Mel/VelNCT01242267
Escalating Doses of Thalidomide in Conjunction With Bortezomib and HIgh Dose Melphalan for BSCT
A Phase 1/2 study testing Thalidomide+Melphalan +Bortezomib+stem cell transplant in people with Multiple Myeloma, run by Hackensack Meridian Health at 1 site in United States.
Trial summary
The primary objective of this study is to: Determine the maximum tolerated dose of thalidomide used in conjunction with dose-intense melphalan, bortezomib and autologous (syngeneic) HSC support in the salvage therapy of patients who failed a prior treatment with dose-intense melphalan The secondary objectives of this… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Thalidomide+Melphalan +Bortezomib+stem cell transplant
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 11 May 2010to 20 Jan 2016
- Phase
- Phase 1/2
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Each patient must meet all of the following inclusion criteria to be enrolled in the study:
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
- Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control as described in the S.T.E.P.S program. Participation in the program is required.
- Male subject agrees to use an acceptable method for contraception for the duration of the study as described in the S.T.E.P.S program. Participation in the program is required.
- Confirmed diagnosis of multiple myeloma, or plasma cell leukemia.
- Show progression of disease after a previous dose-intense cycle of melphalan, or less than a complete response after a prior cycle of dose-intense melphalan. Patients may have received more than on prior autologous transplant with high-dose melphalan.
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- May have received intervening therapies after disease progression after dose-intense melphalan and before enrollment in this protocol.
- Recovery from complications of salvage therapy, if administered.
- Age: ≥18 yrs but <76 yrs at the time of melphalan administration.
- Gender: There is no gender restriction.
- Availability of >2x106 autologous peripheral blood CD34+ cells/kg or a syngeneic donor meeting eligibility criteria for syngeneic donation.
- Syngeneic transplantation is preferred.
Who cannot join
- Patients meeting any of the following exclusion criteria are not to be enrolled in the study.
- Cytotoxic chemotherapy or radiotherapy within 21 days of initiating treatment in this study.
- Prior dose-intense therapy within 56 days of initiating treatment in this study.
- Uncontrolled bacterial, viral, fungal or parasitic infections .
- Uncontrolled CNS metastases.
- Known amyloid deposition in heart.
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- Organ dysfunction:
- LVEF <40% or cardiac failure not responsive to therapy. DLCO <50% of predicted and/or receiving supplementary continuous oxygen. Evidence of hepatic synthetic dysfunction, or total bilirubin >2x or AST >3x ULN.
- Measured creatinine clearance <20 ml/min. Sensory peripheral neuropathy grade 4 within 14 days of enrollment.
- Karnofsky score <70% unless as a result of bone disease directly caused by myeloma.
- Life expectancy limited by another co-morbid illness.
- Diagnosed or treated for another malignancy within 2 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy
- Female subject is pregnant or breast-feeding (women) or unwilling to use acceptable birth control methods (men or women) for twelve months after treatment or unwilling to participate in the S.T.E.P.S program.
- Documented hypersensitivity to melphalan, thalidomide or to bortezomib, boron or mannitol or any components of the formulation
- Patients unable or unwilling to provide consent
- Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
- Patient has received other investigational drugs with 14 days before enrollment
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
Trial locations and contacts
1 site in 1 country.
United States1 site
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601
About this study
Official title: A Phase I/II Study of Escalating Doses of Thalidomide in Conjunction With Bortezomib and HIgh Dose Melphalan as a Conditioning Regimen for Autologous Peripheral Blood Stem Cell Transplantation in Patients With Advanced Multiple Myeloma
The primary objective of this study is to:
- Determine the maximum tolerated dose of thalidomide used in conjunction with dose-intense melphalan, bortezomib and autologous (syngeneic) HSC support in the salvage therapy of patients who failed a prior treatment with dose-intense melphalan
Read more
The secondary objectives of this study are to:
- Determine the toxicities resulting from administration of combinations of thalidomide, bortezomib and melphalan
- Determine the complete response (CR) and very good partial response (VgPR) rate in patients undergoing ASCT using thalidomide, bortezomib and melphalan
- Evaluate the treatment-free interval after treatment with the combination of thalidomide, bortezomib and melphalan
Read the detailed description
VELCADE™ (bortezomib) for Injection is a small molecule proteasome inhibitor developed by Millennium Pharmaceuticals, Inc., (Millennium) as a novel agent to treat human malignancies. VELCADE is currently approved by the United States Food and Drug Administration (US FDA) and it is registered in Europe for the treatment of multiple myeloma patients who have received at least one prior therapy.
By inhibiting a single molecular target, the proteasome, bortezomib affects multiple signaling pathways. The anti-neoplastic effect of bortezomib likely involves several distinct mechanisms, including inhibition of cell growth and survival pathways, induction of apoptosis, and inhibition of expression of genes that control cellular adhesion, migration and angiogenesis. Thus, the mechanisms by which bortezomib elicits its antitumor activity may vary among tumor types, and the extent to which each affected pathway is critical to the inhibition of tumor growth could also differ. Bortezomib has a novel pattern of cytotoxicity in National Cancer Institute (NCI) in vitro and in vivo assays (Adams et al., 1999). In addition, bortezomib has cytotoxic activity in a variety of xenograft tumor models, both as a single agent and in combination with chemotherapy and radiation (Steiner et al., 2001; Teicher et al., 1999; Cusack et al., 2001; LeBlanc et al., 2002; Pink et al., 2002). Notably, bortezomib induces apoptosis in cells that over express bcl-2, a genetic trait that confers unregulated growth and resistance to conventional chemotherapeutics (McConkey et al., 1999).
Bortezomib is thought to be efficacious in multiple myeloma via its inhibition of nuclear factor κB (NF-κB) activation, its attenuation of interleukin-6 (IL-6)-mediated cell growth, a direct apoptotic effect, and possibly anti-angiogenic and other effects.
- Conditions
- Multiple Myeloma
- Being tested
- Thalidomide+Melphalan +Bortezomib+stem cell transplant
- Keywords
- multiple myeloma, transplant, Multiple myeloma patients undergoing transplant
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Thalidomide+Melphalan +Bortezomib+stem cell transplantDrug
Five days prior to transplant, the patient starts thalidomide. Dose range will be from 600mg for 5 days, to 1000mg for 5 days. Thalidomide dose is increased after groups of 3 to 6 patients have been treated. 4 days before the transplant and again on the day before the transplant the patient will be given bortezomib (VELCADE) intravenously at a dose of 1.6 mg/m2 (mg/m2 means that the dose will be calculated based on the patient's height and weight). 2 days before transplant the patient will be given melphalan 200 mg/m2 intravenously. Dexamethasone is given before the VELCADE and the melphalan.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 | Experimental | Phase 1 including Thalidomide Dose Levels of 600, 800, 1000 mg. Three patients will be entered at each dose level sequentially with a maximum of six patients enrolled at the highest dose level that defines dose-limiting toxicity. The starting dose will be 600mg/d x 5 days (dose level 1) given on days -5 to -1 before transplantation. Doses will be escalated in sequential order as listed below through cohorts of patients. Receives: Drug: Thalidomide+Melphalan +Bortezomib+stem cell transplant |
| Phase 2 | Experimental | Phase 2 Thalidomide Dose Level of 1000 mg. The maximum dose to be tested is 1000mg. When the MTD is defined, an additional 40 patients will be enrolled at this level. The first 3 patients of this cohort of 40 patients will be assessed for DLT (2 of 6 patients experiencing DLT at this dose will require dose-de-escalation as described above, and the phase II portion of the study re-initiated at the newly defined MTD). Receives: Drug: Thalidomide+Melphalan +Bortezomib+stem cell transplant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose of Thalidomide
Maximum tolerated dose of thalidomide used in conjunction with dose-intense melphalan, bortezomib and autologous (syngeneic) HSC support in the salvage therapy of patients who failed a prior treatment with dose-intense melphalan
Measured: Dose escalation will be based on the assessment of tolerability determined after the last patient of each cohort reaches day +21.
Secondary outcomes (3)
Complete Response (CR) and Very Good Partial Response (VgPR) Rate
The complete response (CR) and very good partial response (VgPR) rate in patients undergoing ASCT using thalidomide, bortezomib and melphalan
Measured: Assessments will be made from Day +28 after transplantation for 3 months and then at 3 month intervals until demonstration of disease progression and initiation of further therapy, an average of 9 months
Toxicity Assessment
Assessment of the toxicities resulting from administration of combinations of thalidomide, bortezomib and melphalan
Measured: Patients will be hospitalized or in the outpatient transplant facility until engraftment and resolution of serious adverse events, a median of 16 (range, 11-24) days
Treatment Free Interval/PFS
The treatment-free interval after treatment with the combination of thalidomide, bortezomib and melphalan
Measured: PFS was defined as the time from ASCT to disease progression or death from any cause, an average of 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2010 (estimated)
- Study start11 May 2010
- Primary completion20 Jan 2016
- Study completion20 Jan 2016
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.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hackensack Meridian Health
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Scott D Rowley, MD, Principal investigator, John Theurer Cancer Center at Hackensack Univ Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01242267
- Sponsor's protocol ID
- Pro00001215
- Acronym
- Thal/Mel/Vel
- Status last verified
- Mar 2026
- First submitted
- 15 Nov 2010
- Last updated
- 2 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of Escalating Doses of Thalidomide in Conjunction With Bortezomib and HIgh Dose Melphalan as a Conditioning Regimen for Autologous Peripheral Blood Stem Cell Transplantation in Patients With Advanced Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01242267
- Acronym / sponsor ID
- Thal/Mel/Vel / Pro00001215
- Conditions
- Multiple Myeloma
- Keywords
- multiple myeloma, transplant, Multiple myeloma patients undergoing transplant
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Hackensack Meridian HealthUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- 11 May 2010 (actual)
- Primary completion
- 20 Jan 2016 (actual)
- Study completion
- 20 Jan 2016 (actual)
- First posted
- 16 Nov 2010 (estimated)
- Results
- Posted 3 Jan 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to:
- Determine the maximum tolerated dose of thalidomide used in conjunction with dose-intense melphalan, bortezomib and autologous (syngeneic) HSC support in the salvage therapy of patients who failed a prior treatment with dose-intense melphalan
The secondary objectives of this study are to:
- Determine the toxicities resulting from administration of combinations of thalidomide, bortezomib and melphalan
- Determine the complete response (CR) and very good partial response (VgPR) rate in patients undergoing ASCT using thalidomide, bortezomib and melphalan
- Evaluate the treatment-free interval after treatment with the combination of thalidomide, bortezomib and melphalan
Detailed description
VELCADE™ (bortezomib) for Injection is a small molecule proteasome inhibitor developed by Millennium Pharmaceuticals, Inc., (Millennium) as a novel agent to treat human malignancies. VELCADE is currently approved by the United States Food and Drug Administration (US FDA) and it is registered in Europe for the treatment of multiple myeloma patients who have received at least one prior therapy.
By inhibiting a single molecular target, the proteasome, bortezomib affects multiple signaling pathways. The anti-neoplastic effect of bortezomib likely involves several distinct mechanisms, including inhibition of cell growth and survival pathways, induction of apoptosis, and inhibition of expression of genes that control cellular adhesion, migration and angiogenesis. Thus, the mechanisms by which bortezomib elicits its antitumor activity may vary among tumor types, and the extent to which each affected pathway is critical to the inhibition of tumor growth could also differ. Bortezomib has a novel pattern of cytotoxicity in National Cancer Institute (NCI) in vitro and in vivo assays (Adams et al., 1999). In addition, bortezomib has cytotoxic activity in a variety of xenograft tumor models, both as a single agent and in combination with chemotherapy and radiation (Steiner et al., 2001; Teicher et al., 1999; Cusack et al., 2001; LeBlanc et al., 2002; Pink et al., 2002). Notably, bortezomib induces apoptosis in cells that over express bcl-2, a genetic trait that confers unregulated growth and resistance to conventional chemotherapeutics (McConkey et al., 1999).
Bortezomib is thought to be efficacious in multiple myeloma via its inhibition of nuclear factor κB (NF-κB) activation, its attenuation of interleukin-6 (IL-6)-mediated cell growth, a direct apoptotic effect, and possibly anti-angiogenic and other effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase 1 | Experimental | Drug: Thalidomide+Melphalan +Bortezomib+stem cell transplantPhase 1 including Thalidomide Dose Levels of 600, 800, 1000 mg. Three patients will be entered at each dose level sequentially with a maximum of six patients enrolled at the highest dose level that defines dose-limiting toxicity. The starting dose will be 600mg/d x 5 days (dose level 1) given on days -5 to -1 before transplantation. Doses will be escalated in sequential order as listed below through cohorts of patients. |
| Phase 2 | Experimental | Drug: Thalidomide+Melphalan +Bortezomib+stem cell transplantPhase 2 Thalidomide Dose Level of 1000 mg. The maximum dose to be tested is 1000mg. When the MTD is defined, an additional 40 patients will be enrolled at this level. The first 3 patients of this cohort of 40 patients will be assessed for DLT (2 of 6 patients experiencing DLT at this dose will require dose-de-escalation as described above, and the phase II portion of the study re-initiated at the newly defined MTD). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Each patient must meet all of the following inclusion criteria to be enrolled in the study:
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
- Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control as described in the S.T.E.P.S program. Participation in the program is required.
- Male subject agrees to use an acceptable method for contraception for the duration of the study as described in the S.T.E.P.S program. Participation in the program is required.
- Confirmed diagnosis of multiple myeloma, or plasma cell leukemia.
Key exclusion criteria (18 listed)
- Patients meeting any of the following exclusion criteria are not to be enrolled in the study.
- Cytotoxic chemotherapy or radiotherapy within 21 days of initiating treatment in this study.
- Prior dose-intense therapy within 56 days of initiating treatment in this study.
- Uncontrolled bacterial, viral, fungal or parasitic infections .
- Uncontrolled CNS metastases.
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 |
|---|---|---|
| Thalidomide+Melphalan +Bortezomib+stem cell transplantFive days prior to transplant, the patient starts thalidomide. Dose range will be from 600mg for 5 days, to 1000mg for 5 days. Thalidomide dose is increased after groups of 3 to 6 patients have been treated. 4 days before the transplant and again on the day before the transplant the patient will be given bortezomib (VELCADE) intravenously at a dose of 1.6 mg/m2 (mg/m2 means that the dose will be calculated based on the patient's height and weight). 2 days before transplant the patient will be given melphalan 200 mg/m2 intravenously. Dexamethasone is given before the VELCADE and the melphalan. | Drug | Phase 1, Phase 2 |
Primary outcome
Maximum Tolerated Dose of Thalidomide
Time frame: Dose escalation will be based on the assessment of tolerability determined after the last patient of each cohort reaches day +21.
Maximum tolerated dose of thalidomide used in conjunction with dose-intense melphalan, bortezomib and autologous (syngeneic) HSC support in the salvage therapy of patients who failed a prior treatment with dose-intense melphalan
3 secondary outcomes
Complete Response (CR) and Very Good Partial Response (VgPR) Rate
Time frame: Assessments will be made from Day +28 after transplantation for 3 months and then at 3 month intervals until demonstration of disease progression and initiation of further therapy, an average of 9 months
Toxicity Assessment
Time frame: Patients will be hospitalized or in the outpatient transplant facility until engraftment and resolution of serious adverse events, a median of 16 (range, 11-24) days
Treatment Free Interval/PFS
Time frame: PFS was defined as the time from ASCT to disease progression or death from any cause, an average of 9 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2026.
- 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.
Scott D Rowley, MD principal investigator
John Theurer Cancer Center at Hackensack Univ Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Thalidomide+Melphalan +Bortezomib+stem cell transplant in people with Multiple Myeloma, run by Hackensack Meridian Health at 1 site in United States.
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 12 inclusion and 18 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: finished, as of the sponsor's last update on 2 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 3 Jan 2023). 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?
Maximum Tolerated Dose of Thalidomide (time frame: Dose escalation will be based on the assessment of tolerability determined after the last patient of each cohort reaches day +21.). 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 2 Apr 2026.