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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by University of Rochester
Sponsor:
Information provided by (Responsible Party):
University of Rochester
ClinicalTrials.gov Identifier:
NCT01182233
First received: August 3, 2010
Last updated: October 14, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Radiation: Total Skeletal Irradiation
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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 Marrow Irradiation (TMI) Administered Via Helical Tomotherapy (HT)Plus High-Dose Melphalan and Amifostine Before AHSCT2

Resource links provided by NLM:


Further study details as provided by University of Rochester:

Primary Outcome Measures:
  • Define the maximum tolerated dose of a derived high dose therapy regimen [ Time Frame: Day 100 post transplant ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Determine the dose-limiting toxicity (DLT) of TSI-HT therapy [ Time Frame: Day 100 post transplant ] [ Designated as safety issue: Yes ]
    This objective will also include detailed short and long term assessment of hematopoiesis even if it is not the dose limiting toxicity.

  • Compare toxicities to those produced by the AHSCT1 regimen [ Time Frame: Day 100 post transplant ] [ Designated as safety issue: Yes ]
    Determine if quantity and severity of toxicities of TSI regimen are less than toxicities experienced in AHSCT1.

  • Compare antitumor results obtained by TSI-HT before AHSCT [ Time Frame: End of study (June 2013 - anticipated) ] [ Designated as safety issue: No ]
    Compare using standard outcome parameters (ie; response rate, relapse rate, disease-free survival or progression-free survival and overall survival) to high dose chemotherapy/AHSCT1


Estimated Enrollment: 30
Study Start Date: June 2010
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Total Skeletal Irradiation Radiation: Total Skeletal Irradiation
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01182233

Locations
United States, New York
University of Rochester Medical Center Recruiting
Rochester, New York, United States, 14642
Contact: Robin Boerman    585-273-1507    Robin_Boerman@urmc.rochester.edu   
Contact: Sarah Duffy, MS, CCRP    585-275-3817    sarah_duffy@urmc.rochester.edu   
Principal Investigator: Becker Michael, MD         
Sponsors and Collaborators
University of Rochester
Investigators
Principal Investigator: Gordon Phillips, MD University of Rochester
  More Information

No publications provided

Responsible Party: University of Rochester
ClinicalTrials.gov Identifier: NCT01182233     History of Changes
Other Study ID Numbers: 30850
Study First Received: August 3, 2010
Last Updated: October 14, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Rochester:
Multiple Myeloma
Autologous Hematopoietic Stem Cell Transplant
Total Skeletal Irradiation
High dose chemotherapy

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

ClinicalTrials.gov processed this record on July 26, 2014