Escalating Doses of Thalidomide in Conjunction With Bortezomib and HIgh Dose Melphalan for BSCT

NCT01242267 | Completed Phase 1 Results DMC

• 1 other identifier: Pro00001215
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief 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 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

Conditions

Multiple Myeloma

Keywords

multiple myeloma; transplant; Multiple myeloma patients undergoing transplant

Outcome Measures

Primary Outcomes (1)

• 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

  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

  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

  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

  PFS was defined as the time from ASCT to disease progression or death from any cause, an average of 9 months

Study Arms (2)

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.

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).

Drug: Thalidomide+Melphalan +Bortezomib+stem cell transplant

Interventions

Thalidomide+Melphalan +Bortezomib+stem cell transplant DRUG

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.

Phase 1; Phase 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Hackensack Meridian Health: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

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

Results Point of Contact

• Title: Joshua Zenreich
• Organization: Hackensack Meridan Health

Joshua.Zenreich@hmhn.org

5519964248

Study Officials

• Scott D Rowley, MD

  John Theurer Cancer Center at Hackensack Univ Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2010
• First Posted: November 16, 2010
• Study Start: May 11, 2010
• Primary Completion: January 20, 2016
• Study Completion: January 20, 2016
• Last Updated: April 2, 2026
• Results First Posted: January 3, 2023

Record last verified: 2026-03

Locations

US (1)