Total Skeletal Irradiation in Multiple Myeloma Before Second Autologous Hematopoietic Stem Cell Transplantation

NCT01182233 | Terminated Phase 1

• 1 other identifier: 30850
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to improve the efficacy of the HDC regimen by adding a novel, "targeted" means administering a variation of total body irradiation (TBI) radiation i.e., total skeletal irradiation (TSI) administered by helical tomotherapy (HT) before, and in addition to the current standard of HDC, at a dose of 200 mg/m2 (HDMel200). The underlying postulate of this endeavor is that TSI-HT will provide additional cytoreduction to HDMel alone, without producing additional (serious) toxicity. We will utilize a classical Phase I study design (i.e., dose escalation) in myeloma patients undergoing AHSCT2 to define a maximum tolerated dose (MTD) and dose limiting toxicity (DLT). Finally, although comparisons to other therapies are not typical (and/or feasible) for a Phase I study, we will compare, whenever possible, both the toxicity and the antimyeloma activity of the AHSCT2 to AHSCT1. This protocol will standardize, as much as possible the use of AHSCT2 both as a "tandem" and "salvage" procedure. Since sufficient AHSC (CD34+ cells) are routinely collected in adequate numbers for multiple AHSCTs, but recently used infrequently, it is important to work towards defining the optimal utilization of this resource.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Autologous Hematopoietic Stem Cell Transplant; Total Skeletal Irradiation; High dose chemotherapy

Outcome Measures

Primary Outcomes (1)

• Define the maximum tolerated dose of a derived high dose therapy regimen

  MTD of high dose therapy consisting of escalating doses of Total Skeletal Irradiation administered via Helical Tomotherapy, followed by standard high dose chemotherapy of high dose Melphalan (200mg/m2) with amifostine cytoprotection before AHSCT.

  Day 100 post transplant

Secondary Outcomes (3)

• Determine the dose-limiting toxicity (DLT) of TSI-HT therapy

  Day 100 post transplant

• Compare toxicities to those produced by the AHSCT1 regimen

  Day 100 post transplant

• Compare antitumor results obtained by TSI-HT before AHSCT

  End of study (June 2013 - anticipated)

Study Arms (1)

Total Skeletal Irradiation

EXPERIMENTAL

Three subjects determined to be eligible for study and agree to participate are assigned to receive 200 cGy of TSI-HT for 5 days. If this dose level is well tolerated in the first 3 subjects, the dose will be increased and given over 5 days. The dose will continue to be increased until the maximum toelrated dose is reached.

Radiation: Total Skeletal Irradiation

Interventions

Total Skeletal Irradiation RADIATION

Escalating doses of TSI starting at 200cGy (escalating up to 400cGy unless maximum tolerated dose is determined in lower dose level) in cohort 1 over 5 days followed by high dose melphalan and cytoprotection followed by autologous hematopoietic stem cell transplant

Total Skeletal Irradiation

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \</= 70 years
• Documented myeloma confirmed at protocol entry
• Adequate presence of \>/=2.0x10e6/kg cryopreserved CD34+ cells
• Adequate organ function
• Prior therapy is allowed as long as the organ function parameters are maintained and/or excessive radiation exposure is not produced
• Chemosensitivity

You may not qualify if:

• Uncontrolled infection
• Pregnant or lactating females
• Patients in \>/= very good partial response after initial primary non-transplant therapy and/or AHSCT1
• Patients unwilling to practice adequate forms of contraception if clinically indicated

Sponsors & Collaborators

• University of Rochester: lead

Study Sites (1)

University of Rochester Medical Center

Rochester, New York, 14642, 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

Study Officials

• Gordon Phillips, MD

  University of Rochester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, Division of Hematology/Oncology

Study Record Dates

• First Submitted: August 3, 2010
• First Posted: August 16, 2010
• Study Start: June 1, 2010
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: May 17, 2016

Record last verified: 2015-04

Locations

US (1)