High Dose Sequential Therapy and Autologous Stem Cell Rescue for Multiple Myeloma

NCT00586014 | Completed Phase 2 DMC

• 1 other identifier: 0074
• Study Type: interventional
• Target: 91
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this phase II study is to assess the toxicity and efficacy of sequentially administered high dose chemotherapy followed by autologous stem cell rescue in the treatment of multiple myeloma. Prior studies have shown that dose-intensified melphalan can produce higher response rates and complete remission in some patients. Over the past several years, multiple phase II studies utilizing high dose chemotherapy or high dose chemo-radiotherapy with autologous marrow or peripheral blood stem cell rescue have demonstrated improved response rates and survival rates compared to historical controls. Recently a prospective randomized trial has demonstrated improved response rates, response duration and overall survival utilizing high dose therapy with autologous bone marrow support compared to standard chemotherapy. The primary cause of failure is relapse and it is unclear how many, if any, patients are cured by this approach. Based on observations of efficacy in Hodgkin's Disease, Non-Hodgkin's Lymphoma, and breast cancer, an approach utilizing sequential high dose chemotherapy in multiple myeloma was developed. This protocol tests the sequential regimen in multiple myeloma patients who have responded to a standard dose chemotherapy regimen prior to enrollment.

Conditions

Multiple Myeloma

Keywords

Multiple myeloma; Autologous Stem Cell Transplant

Outcome Measures

Primary Outcomes (1)

• To evaluate the progression free survival at one year in multiple myeloma patients who receive sequentially administered high dose cyclophosphamide and VP-16 followed by high-dose BCNU (Carmustine) plus Melphalan

  4 years

Secondary Outcomes (2)

• To evaluate the response rates of multiple myeloma patients to this sequentially administered high dose chemotherapy.

  4 years

• To evaluate the safety and toxicity of this sequential high dose chemotherapy program in multiple myeloma patients.

  4 years

Study Arms (1)

I

EXPERIMENTAL

High-dose sequential cyclophosphamide and VP-16 followed by myeloablation with high-dose BCNU and melphalan with autologous stem cell transplant

Procedure: High-Dose Sequential Chemotherapy followed by ASCT

Interventions

High-Dose Sequential Chemotherapy followed by ASCT PROCEDURE

Patient will receive Cyclophosphamide(4 g/m2 over 2 hours) and blood progenitor cell collection (day -49). G-CSF (10 mcg/kg/d) will be administered SQ. A six hour leukapheresis will be performed,cells will undergo CD34+ cell selection, patients will receive high dose VP-16 (Etopophos)(day -28)(2 g/m2 over 4 hours)and G-CSF (5 mcg/kg/d) will be administered SQ two days following VP-16. The an IV of sulfamethoxazole-trimethoprim 1 ampule BID for 5 days (Day -5). BCNU 500 mg/m2 IV over 2 hours (Day -4). Melphalan (Day -2) will be administered IV (200 mg/m2 over 20 minutes). The frozen peripheral blood mononuclear cells will be transfused on Day 0. Day +1: G-CSF 5 mcg/kg/d SQ for 3 days.

I

Eligibility Criteria

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

You may qualify if:

• All patients must receive multi-agent based chemotherapy, preferably VAD, as cytoreduction prior to transplantation. The time from the last chemotherapy administration must be greater than 21 days. Patients with recurrent myeloma must have sensitive disease as demonstrated by a decrease in serum or urine paraprotein levels of \>50% or a decrease in bone marrow plasmacytosis to less than 20%. Patients with newly diagnosed myeloma may have stable (but not progressive) disease following VAD.
• Patients must have their pathology reviewed and the diagnosis of multiple myeloma confirmed at the transplant center. Patients with smoldering multiple myeloma or benign monoclonal gammopathy of unknown significance will be excluded from this study.
• Performance status: -CALGB 0.1 or Karnofsky greater than 70%
• Patients must have serum creatinine \< 2 x upper limit of normal, bilirubin \< 2 x upper limit of normal, transaminases \< 2 x upper limit of normal, MUGA resting EF \> 50% or more than a 5% increase with exercise if \<50%, DLCO \> 60%

You may not qualify if:

• Patients who have undergone bone marrow transplantation previously will not be eligible.
• Patients with HIV, HBsAG positive
• Pregnant or lactating women
• Patients with other medical or psychiatric disorders which would seriously compromise tolerance to this protocol.

Sponsors & Collaborators

• Duke University: lead

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

Study Officials

• Nelson Chao, MD

  Duke Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2007
• First Posted: January 4, 2008
• Study Start: May 1, 1997
• Primary Completion: January 1, 2006
• Study Completion: February 1, 2008
• Last Updated: July 8, 2014

Record last verified: 2013-05