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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01182233
Recruitment Status : Terminated (low enrollment)
First Posted : August 16, 2010
Last Update Posted : May 17, 2016
Information provided by (Responsible Party):
Gordon Phillips, MD, University of Rochester

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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Radiation: Total Skeletal Irradiation Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of a Method Designed to Improve Outcome of HD Chemotherapy and AHSCT for Patients With Myeloma: Total Marrow Irradiation Administered Via Helical Tomotherapy Plus High-Dose Melphalan and Amifostine Before AHSCT2
Study Start Date : June 2010
Actual Primary Completion Date : September 2014
Actual Study Completion Date : September 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
Drug Information available for: Melphalan

Arm Intervention/treatment
Experimental: Total Skeletal Irradiation
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
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

Primary Outcome Measures :
  1. Define the maximum tolerated dose of a derived high dose therapy regimen [ Time Frame: Day 100 post transplant ]
    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 :
  1. Determine the dose-limiting toxicity (DLT) of TSI-HT therapy [ Time Frame: Day 100 post transplant ]
    This objective will also include detailed short and long term assessment of hematopoiesis even if it is not the dose limiting toxicity.

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

  3. Compare antitumor results obtained by TSI-HT before AHSCT [ Time Frame: End of study (June 2013 - anticipated) ]
    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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01182233

United States, New York
University of Rochester Medical Center
Rochester, New York, United States, 14642
Sponsors and Collaborators
University of Rochester
Principal Investigator: Gordon Phillips, MD University of Rochester

Responsible Party: Gordon Phillips, MD, Professor of Medicine, Division of Hematology/Oncology, University of Rochester Identifier: NCT01182233     History of Changes
Other Study ID Numbers: 30850
First Posted: August 16, 2010    Key Record Dates
Last Update Posted: May 17, 2016
Last Verified: April 2015

Keywords provided by Gordon Phillips, MD, 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
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs