Auto Transplant High Dose Melphalan vs High Dose Melphalan+Bortezomib in Pts With Multiple Myeloma Age 65 Years or Older

• ClinicalTrials.gov Identifier: NCT01453088
• Recruitment Status: Active, not recruiting
• First Posted: October 17, 2011
• Last Update Posted: May 9, 2022
• Sponsor: Hackensack Meridian Health
• Information provided by (Responsible Party): Hackensack Meridian Health

Study Description

Brief Summary:

In this study the investigators are comparing this standard regimen to the newly established regimen of melphalan and bortezomib.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Drug: Melphalan; Drug: Bortezomib	Phase 2

Detailed Description:

In this study the investigators are comparing this standard regimen to the newly established regimen of melphalan and bortezomib.

Conditioning Regimens:

Treatment arm A Melphalan is administered at a dose of 200mg/m2 by rapid intravenous infusion via a central or peripheral vein over 30 minutes to one hour.

Melphalan will be given as a single dose (not split over 2 or more days) and given on day-1.

Dosing will be based on body surface area calculated using actual body weight

Stem cell infusion:

Stem cell infusion will occur on day 0 and will be at least 20 hours after the infusion of melphalan. The infusion of peripheral blood stem cells will be done in accordance with the Blood and Marrow Transplant program standard operating procedures.

Filgrastim will be administered at a dose of 5 mcg/kg (rounded to vial size) every other day starting on day+3 then daily starting on day 9 until engraftment (at least).

Treatment arm B

Bortezomib:

Bortezomib is administered by rapid I.V. push (over 3-5 seconds) via a central or peripheral vein into a flowing saline line. Bortezomib will be administered any time on day -4 and at least 20 hrs after the start of the melphalan infusion on day -1.

Dosing will be based on actual body weight. Dexamethasone is administered at a dose of 20 mg IV prior to each bortezomib infusion.

Melphalan:

Melphalan is administered at a dose of 200mg/m2 by rapid intravenous infusion via a central or peripheral vein over 30 minutes to one hour.

Melphalan will be given as a single dose (not split over 2 or more days) and given of day-2.

Dosing will be based body surface area calculated using actual body weight

Stem cell infusion:

Stem cell infusion will occur on day 0 and will be at least 18 hours after the infusion of the bortezomib. The infusion of peripheral blood stem cells will be done in accordance with the Blood and Marrow Transplant program standard operating procedures.

Filgrastim will be administered at a dose of 5 mcg/kg (rounded to vial size) every other day starting on day+3 then daily starting on day 9 until engraftment (at least).

Post-transplant Supportive Care will be administered in accordance to the Blood and Marrow Transplant program standard operating procedures.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 62 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: (PRO#11307) Phase III Randomized Study of Autologous Stem Cell Transplantation With High-dose Melphalan Versus High-dose Melphalan and Bortezomib in Patients With Multiple Myeloma 65 Year or Older
• Actual Study Start Date: June 24, 2010
• Actual Primary Completion Date: May 1, 2022
• Estimated Study Completion Date: May 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Treatment A; Melphalan is administered at a dose of 200mg/m2 by rapid intravenous infusion via a central or peripheral vein over 30 minutes to one hour. Melphalan will be given as a single dose (not split over 2 or more days) and given on day-1. Dosing will be based on body surface area calculated using actual body weight Stem cell infusion: Stem cell infusion will occur on day 0 and will be at least 20 hours after the infusion of melphalan. The infusion of peripheral blood stem cells will be done in accordance with the Blood and Marrow Transplant program standard operating procedures. Filgrastim will be administered at a dose of 5 mcg/kg (rounded to vial size) every other day starting on day+3 then daily starting on day 9 until engraftment (at least).	Drug: Melphalan; Melphalan is administered at a dose of 200mg/m2 by rapid intravenous infusion via a central or peripheral vein over 30 minutes to one hour. Melphalan will be given as a single dose (not split over 2 or more days) and given on day-1. Dosing will be based on body surface area calculated using actual body weight Stem cell infusion: Stem cell infusion will occur on day 0 and will be at least 20 hours after the infusion of melphalan. The infusion of peripheral blood stem cells will be done in accordance with the Blood and Marrow Transplant program standard operating procedures. Filgrastim will be administered at a dose of 5 mcg/kg (rounded to vial size) every other day starting on day+3 then daily starting on day 9 until engraftment (at least).; Other Name: Phenylalanine mustard
Experimental: Treatment Arm B; Bortezomib: Bortezomib is administered by rapid I.V. push (over 3-5 seconds) via a central or peripheral vein into a flowing saline line. Bortezomib will be administered any time on day -4 and at least 20 hrs after the start of the melphalan infusion on day -1.	Drug: Bortezomib; Bortezomib: Bortezomib is administered by rapid I.V. push (over 3-5 seconds) via a central or peripheral vein into a flowing saline line. Bortezomib will be administered any time on day -4 and at least 20 hrs after the start of the melphalan infusion on day -1.; Other Name: Velcade

Outcome Measures

Primary Outcome Measures :

1. To compare the progression free survival of elderly patients with multiple myeloma treated with either high-dose melphalan versus high-dose melphalan and bortezomib. [ Time Frame: Participants will be followed post transplant for a minimum of 2 years, and after that may be monitored as part of the study indefinitely ]

Secondary Outcome Measures :

1. To compare the response rate, overall survival and toxicity of high-dose melphalan versus high-dose melphalan and bortezomib [ Time Frame: 1 year ]

Eligibility Criteria

• Ages Eligible for Study: 60 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Confirmed diagnosis of multiple myeloma less than 12 months since initiation of systemic therapy
• Age ≥60 years at time of transplantation
• KPS 70-100%
• Recovery from complications of prior therapy

Exclusion Criteria:

• Diagnosis other than multiple myeloma
• Chemotherapy or radiotherapy within 8 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
• FVC, FEV1 or DLCO < 40% of predicted and/or receiving supplementary continuous oxygen
• Evidence of hepatic synthetic dysfunction or total bilirubin > 2x or AST > 3x ULN
• Measured creatinine < 20ml/min
• Sensory peripheral neuropathy grade 4 within 14 days of enrollment
• Karnofsky score < 70%
• Life expectancy limited by other co-morbid illnesses

Contacts and Locations

Locations

United States, District of Columbia

Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

Washington, District of Columbia, United States, 20057

United States, New Jersey

Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

Sponsors and Collaborators

Hackensack Meridian Health

Investigators

• Principal Investigator: Michele Donato, MD; John Theurer Cancer Center at Hackensack University Medical Center

More Information

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Teicher BA, Ara G, Herbst R, Palombella VJ, Adams J. The proteasome inhibitor PS-341 in cancer therapy. Clin Cancer Res. 1999 Sep;5(9):2638-45.

Tricot G, Jagannath S, Vesole DH, Crowley J, Barlogie B. Relapse of multiple myeloma after autologous transplantation: survival after salvage therapy. Bone Marrow Transplant. 1995 Jul;16(1):7-11.

Tricot G, Alberts DS, Johnson C, Roe DJ, Dorr RT, Bracy D, Vesole DH, Jagannath S, Meyers R, Barlogie B. Safety of autotransplants with high-dose melphalan in renal failure: a pharmacokinetic and toxicity study. Clin Cancer Res. 1996 Jun;2(6):947-52.

Tricot G, Spencer T, Sawyer J, Spoon D, Desikan R, Fassas A, Badros A, Zangari M, Munshi N, Anaissie E, Toor A, Barlogie B. Predicting long-term (> or = 5 years) event-free survival in multiple myeloma patients following planned tandem autotransplants. Br J Haematol. 2002 Jan;116(1):211-7. doi: 10.1046/j.1365-2141.2002.03231.x.

Vesole DH, Barlogie B, Jagannath S, Cheson B, Tricot G, Alexanian R, Crowley J. High-dose therapy for refractory multiple myeloma: improved prognosis with better supportive care and double transplants. Blood. 1994 Aug 1;84(3):950-6.

• Responsible Party: Hackensack Meridian Health
• ClinicalTrials.gov Identifier: NCT01453088
• Other Study ID Numbers: PRO# 1307
• First Posted: October 17, 2011
• Last Update Posted: May 9, 2022
• Last Verified: May 2022

Keywords provided by Hackensack Meridian Health:

multiple myeloma; transplant

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Bortezomib; Melphalan; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Myeloablative Agonists; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs