Peripheral Stem Cell Transplant in Treating Patients With Multiple Myeloma

Sponsor

Alliance for Clinical Trials in Oncology (Other)

Overall Status

Completed

CT.gov ID

NCT00028600

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Multiple Myeloma Plasma Cell Neoplasm	Biological: filgrastim Biological: CD34+ cells Drug: cyclophosphamide Drug: fludarabine phosphate Drug: melphalan Drug: methotrexate Drug: tacrolimus	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Autologous Followed By Non-Myeloablative Allogeneic Transplant For Multiple Myeloma

Study Start Date :

Nov 1, 2001

Actual Primary Completion Date :

Jun 1, 2006

Actual Study Completion Date :

Feb 1, 2010

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Treatment-related mortality [6 months]

Secondary Outcome Measures

Treatment Completion Rate [post treatment]
Respone Rate [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 [1,2,3,4, & 6 mon post allo transpl, & 100 d post DLI]
GVHD Incidence [post allo transpl, & pre & post DLI]
Survival [2 years]
Overall and disease free survival will be assessed
Correlation of cytogenetics and response [6, 12 mon then q 1 yr for 3 yrs post allo transpl]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 64 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

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