Peripheral Stem Cell Transplant in Treating Patients With Multiple Myeloma - Full Text View

Sponsor:	Cancer and Leukemia Group B
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Cancer and Leukemia Group B
ClinicalTrials.gov Identifier:	NCT00028600

Purpose

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.

Condition	Intervention	Phase
Multiple Myeloma Plasma Cell Neoplasm	Biological: filgrastim Biological: CD34+ cells Drug: cyclophosphamide Drug: fludarabine phosphate Drug: melphalan Drug: methotrexate Drug: tacrolimus	Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Autologous Followed By Non-Myeloablative Allogeneic Transplant For Multiple Myeloma

Resource links provided by NLM:

Further study details as provided by Cancer and Leukemia Group B:

Primary Outcome Measures:

Treatment-related mortality [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Treatment Completion Rate [ Time Frame: post treatment ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Chimerism Rate [ Time Frame: 1,2,3,4, & 6 mon post allo transpl, & 100 d post DLI ] [ Designated as safety issue: No ]
GVHD Incidence [ Time Frame: post allo transpl, & pre & post DLI ] [ Designated as safety issue: No ]
Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Overall and disease free survival will be assessed
Correlation of cytogenetics and response [ Time Frame: 6, 12 mon then q 1 yr for 3 yrs post allo transpl ] [ Designated as safety issue: No ]

Enrollment:	60
Study Start Date:	November 2001
Estimated Study Completion Date:	March 2023
Primary Completion Date:	February 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Name: 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

Arms

Assigned Interventions

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 Name: 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

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.

Eligibility

Ages Eligible for Study:	up to 64 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00028600

Locations

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

Sponsors and Collaborators

Cancer and Leukemia Group B

National Cancer Institute (NCI)

Investigators

Study Chair:

Kenneth C. Anderson, MD

Dana-Farber Cancer Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Monica M Bertagnolli, Cancer and Leukemia Group B
ClinicalTrials.gov Identifier:	NCT00028600 History of Changes
Other Study ID Numbers:	CDR0000069109, U10CA031946, CALGB-100001
Study First Received:	January 4, 2002
Last Updated:	June 21, 2011
Health Authority:	United States: Federal Government

Keywords provided by Cancer and Leukemia Group B:

refractory multiple myeloma
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:

Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

Cyclophosphamide
Melphalan
Methotrexate
Fludarabine monophosphate
Tacrolimus
Fludarabine
Lenograstim
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on February 12, 2012