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Evaluation of a Method Designed to Improve Outcome of High-Dose Chemotherapy (HDC) and Autologous Hematopoietic Stem Cell Transplantation (AHSCT) for Selected Patients With Myeloma: A Phase I Study Using Total Skeletal Irradiation (TSI) Administered Via Helical Tomotherapy (HT)Plus High-Dose Melphalan and Amifostine Before AHSCT2


Phase 1
18 Years
70 Years
Open (Enrolling)
Both
Multiple Myeloma

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Trial Information

Evaluation of a Method Designed to Improve Outcome of High-Dose Chemotherapy (HDC) and Autologous Hematopoietic Stem Cell Transplantation (AHSCT) for Selected Patients With Myeloma: A Phase I Study Using Total Skeletal Irradiation (TSI) Administered Via Helical Tomotherapy (HT)Plus High-Dose Melphalan and Amifostine Before AHSCT2


While HDC/AHSCT is active most patients eventually relapse; obviously, those with lesser
responses progress as well. Many investigators regard HDC/AHSCT as a "mature" modality a
useful if fixed element in an evolving treatment paradigm that focuses on the introduction
of new (non-HDC/AHSCT) agents with unique mechanisms of action. However, data from several
related sources (including both the syngeneic and second ["tandem" or salvage] AHSCT
experience), suggests that the efficacy of HDC/AHSCT could be improved by obtaining better
cytoreduction of the HDC component, thus prolonging survival and possibly even producing an
increase in cures. However, to do so will require additional attention to the sources of
relapse following HDC/AHSCT, mainly the residual myeloma in the patient, but perhaps also
the inadvertent reinfusion of clonogenic myeloma cells in the AHSCT. For reasons discussed
herein, this study will focus on the former.

We believe that the agents with more potent activity vs. the (multiple) myeloma cancer stem
cell (MM-CSC) and/or their microenvironment are ultimately needed to increase the cure rate
in myeloma. Unfortunately, preliminary data suggest current modalities used in myeloma
therapy are only variably effective vs. these targets, and that newer agents with such
activity are only now becoming available for clinical trials.

The use of these newer agents are most likely to augment, not supplant, current modalities,
lending even more urgency to optimizing existing elements to try to improve the efficacy of
HDC/AHSCT and especially to determine if activity vs. MM-CSC and/or the microenvironment of
these current modalities can be augmented. Radiation seems especially attractive to
re-evaluate, given new, "targeted" methods of administration such as those described herein.
Impetus for this effort comes from the known radiosensitivity of clonogenic myeloma cells
(a population that at least may contain MM-CSC), and especially given the ability of local
radiotherapy to provide local disease control in myeloma, and especially given the ability
of local radiotherapy to cure some patients with solitary plasmacytoma "proving" activity of
radiotherapy vs. MM-CSC in this closely-related diagnosis.

It is important to note that improvement in current modalities may offer better clinical
outcomes even if major effects vs. the MM-CSC and microenvironment interaction are not
produced. We do not currently have the ability to measure such effects; this will not be
part of this trial.


Inclusion Criteria:



- Age
- 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

Exclusion Criteria:

- 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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Description:

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.

Outcome Time Frame:

Day 100 post transplant

Safety Issue:

Yes

Principal Investigator

Gordon Phillips, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Rochester

Authority:

United States: Institutional Review Board

Study ID:

30850

NCT ID:

NCT01182233

Start Date:

June 2010

Completion Date:

Related Keywords:

  • Multiple Myeloma
  • Multiple Myeloma
  • Autologous Hematopoietic Stem Cell Transplant
  • Total Skeletal Irradiation
  • High dose chemotherapy
  • Multiple Myeloma
  • Neoplasms, Plasma Cell

Name

Location

University of Rochester Medical CenterRochester, New York  14642