Peripheral Stem Cell Transplant in Treating Patients With Multiple Myeloma

July 1, 2016 updated by: Alliance for Clinical Trials in Oncology

Autologous Followed By Non-Myeloablative Allogeneic Transplant For Multiple Myeloma

RATIONALE: Peripheral blood stem cell transplant using stem cells from the patient or a donor may be able to replace immune cells that were destroyed by chemotherapy used to kill tumor cells. The donated stem cells may also help destroy any remaining cancer cells (graft-versus-tumor effect).

PURPOSE: This phase II trial is studying how well autologous peripheral stem cell transplant followed by donor peripheral stem cell transplant works in treating patients with multiple myeloma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine whether autologous peripheral blood stem cell transplantation (PBSCT) followed by non-myeloablative allogeneic PBSCT is associated with no more than 20% treatment-related mortality rates at 6 months in patients with multiple myeloma.
  • Determine the response rate of patients treated with this regimen.
  • Determine the percent donor chimerism in patients treated with this regimen.
  • Determine the rate of graft-vs-host disease in patients treated with this regimen.
  • Determine the toxic effects of this regimen in these patients.
  • Determine the disease-free and overall survival of patients treated with this regimen.
  • Determine whether abnormal cytogenetics at presentation correlate with poor response in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive cyclophosphamide IV over 1-2 hours on day 1 and filgrastim (G-CSF) subcutaneously (SC) beginning on day 5 and continuing until peripheral blood stem cell (PBSC) collection is complete.

Approximately 2-4 weeks after PBSC collection, patients receive melphalan IV over 15-30 minutes on day -2. Patients then undergo autologous PBSC transplantation (PBSCT) on day 0. Patients receive G-CSF SC beginning on day 5 and continuing until blood counts recover.

Approximately 2-4 months after autologous PBSCT, patients receive fludarabine IV over 30 minutes on days -7 to -3 and cyclophosphamide IV over 1 hour on days -4 to -3. Patients undergo allogeneic PBSCT on day 0. Patients receive G-CSF SC beginning on day 7 and continuing until blood counts recover.

Patients receive graft-vs-host disease (GVHD) prophylaxis comprising oral tacrolimus twice daily on days -1 to 90 followed by a taper on days 91-150 and methotrexate IV on days 1, 3, and 6.

After day 120, patients with stable or progressive disease and no evidence of active GVHD may receive donor lymphocyte infusion (DLI) over 2 hours. Patients may receive up to 3 DLIs every 8 weeks.

Patients are followed every 3 months for 3 years, every 6 months for 5 years, and then annually for 15 years.

PROJECTED ACCRUAL: A maximum of 63 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94115
        • UCSF Helen Diller Family Comprehensive Cancer Center
    • Delaware
      • Lewes, Delaware, United States, 19958
        • Tunnell Cancer Center at Beebe Medical Center
      • Newark, Delaware, United States, 19713
        • CCOP - Christiana Care Health Services
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60637-1470
        • University of Chicago Cancer Research Center
    • Iowa
      • Iowa City, Iowa, United States, 52242-1002
        • Holden Comprehensive Cancer Center at University of Iowa
    • Maryland
      • Elkton MD, Maryland, United States, 21921
        • Union Hospital Cancer Program at Union Hospital
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - Saint Louis
    • New Jersey
      • Voorhees, New Jersey, United States, 08043
        • Cancer Institute of New Jersey at Cooper - Voorhees
    • New York
      • Buffalo, New York, United States, 14263-0001
        • Roswell Park Cancer Institute
      • New York, New York, United States, 10029
        • Mount Sinai Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7295
        • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
      • Winston-Salem, North Carolina, United States, 27157-1096
        • Wake Forest University Comprehensive Cancer Center
    • Ohio
      • Columbus, Ohio, United States, 43210-1240
        • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224-1791
        • Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 64 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of active multiple myeloma that requires treatment

    • Durie-Salmon stage I, II, and III
  • No more than 1 progression after initial therapy

  • Must have HLA-identical sibling donor (6/6) by serologic typing (A, B, DR)

    • No syngeneic donors
  • Must also be enrolled on protocol CLB-8461 (Cytogenetic Studies in Acute Leukemia)

PATIENT CHARACTERISTICS:

Age:

  • Under 65

Performance status:

  • NCI CTC 0-1

Life expectancy:

  • Not specified

Hematopoietic:

  • Absolute neutrophil count greater than 500/mm^3
  • Platelet count greater than 50,000/mm^3

Hepatic:

  • Bilirubin less than 2 mg/dL
  • AST less than 3 times upper limit of normal (ULN)
  • Alkaline phosphatase less than 3 times ULN

Renal:

  • Creatinine less than 2 mg/dL
  • Creatinine clearance greater than 40 mL/min

Cardiovascular:

  • LVEF at least 30% by MUGA scan

Pulmonary:

  • DLCO greater than 40% of predicted
  • No symptomatic pulmonary disease

Other:

  • HIV negative
  • No uncontrolled diabetes mellitus
  • No active serious infection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • At least 4 weeks since prior chemotherapy
  • Prior alkylating-agent therapy allowed if no more than 12 months duration

Endocrine therapy:

  • Not specified

Radiotherapy:

  • At least 4 weeks since prior radiotherapy

Surgery:

  • At least 4 weeks since prior surgery

Other:

  • All prior therapy no more than 18 months duration

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Autologous + Allogeneic Transplant
autologous PB stem cell transplant followed by non-myeloablative allogeneic transplant fr multiple myeloma
Biological: filgrastim
PBSC collection: 10 ug/kg/d subQ inj D 5 until completion of collection Auto transpl: 5 ug/kg/d subQ inj D 5 until ANC >= 1500/uL for 2d or 5000/uL for 1 d Allo transpl: 5ug/kg/d subQ inj D 7 until ANC > 1000/uL for 3 days Donor pheresis: 10ug/kg/d subQ inj d -5 thru -2
Other Names:
  • G-CSF
Biological: CD34+ cells
2-8,000,000/kg IV infusion allogeneic transplant 2,000,000/kg IV infusion autologous transplant
Drug: cyclophosphamide
4g/sq m IV infusion over 1-2 hrs D 1 for auto, and 1g/sq m/d IV infusion over 1 hr on D -4 thru -3 for allo, transplant prep
Drug: fludarabine phosphate
30mg/sq m/d IVPB over 30 min d -7 thru -3 allo transpl
Drug: melphalan
200mg/sq m IV infusion over 15-30 min D 2 auto transpl
Drug: methotrexate
5mg/sq m/d IV infusion D 1,3,& 6: allo transpl
Drug: tacrolimus
0.03mg/kg PO bid starting dose, D -1 thru +90, then taper thru D +150

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Treatment-related mortality
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment Completion Rate
Time Frame: post treatment
post treatment
Respone Rate
Time Frame: 2-4 wks prior, and 3,6 mon then q 3 mon for 3 yrs, post allo transpl, then q 6 mon for max 15 yrs from study entry
2-4 wks prior, and 3,6 mon then q 3 mon for 3 yrs, post allo transpl, then q 6 mon for max 15 yrs from study entry
Chimerism Rate
Time Frame: 1,2,3,4, & 6 mon post allo transpl, & 100 d post DLI
1,2,3,4, & 6 mon post allo transpl, & 100 d post DLI
GVHD Incidence
Time Frame: post allo transpl, & pre & post DLI
post allo transpl, & pre & post DLI
Survival
Time Frame: 2 years
Overall and disease free survival will be assessed
2 years
Correlation of cytogenetics and response
Time Frame: 6, 12 mon then q 1 yr for 3 yrs post allo transpl
6, 12 mon then q 1 yr for 3 yrs post allo transpl

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alliance for Clinical Trials in Oncology

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Kenneth C. Anderson, MD, Dana-Farber Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2001

Primary Completion (Actual)

June 1, 2006

Study Completion (Actual)

February 1, 2010

Study Registration Dates

First Submitted

January 4, 2002

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

July 4, 2016

Last Update Submitted That Met QC Criteria

July 1, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CALGB-100001
  • U10CA031946 (U.S. NIH Grant/Contract)
  • CDR0000069109 (Registry Identifier: NCI Physician Data Query)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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