Peripheral Stem Cell Transplant in Treating Patients With Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

Autologous Followed By Non-Myeloablative Allogeneic Transplant For Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00028600
• Other study ID #: CALGB-100001
• Secondary ID: U10CA031946CALGB
• Status: Completed
• Phase: Phase 2
• First received: January 4, 2002
• Last updated: July 1, 2016
• Start date: November 2001
• Est. completion date: February 2010

Study information

• Verified date: July 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: February 2010
• Est. primary completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 64 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Plasma Cell Neoplasm
• Plasmacytoma

Intervention

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
• 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
• fludarabine phosphate
30mg/sq m/d IVPB over 30 min d -7 thru -3 allo transpl
• melphalan
200mg/sq m IV infusion over 15-30 min D 2 auto transpl
• methotrexate
5mg/sq m/d IV infusion D 1,3,& 6: allo transpl
• tacrolimus
0.03mg/kg PO bid starting dose, D -1 thru +90, then taper thru D +150

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Columbus	Ohio
United States	Union Hospital Cancer Program at Union Hospital	Elkton MD	Maryland
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware
United States	Mount Sinai Medical Center	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - Saint Louis	St Louis	Missouri
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment-related mortality		6 months	Yes
Secondary	Treatment Completion Rate		post treatment	No
Secondary	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	No
Secondary	Chimerism Rate		1,2,3,4, & 6 mon post allo transpl, & 100 d post DLI	No
Secondary	GVHD Incidence		post allo transpl, & pre & post DLI	No
Secondary	Survival	Overall and disease free survival will be assessed	2 years	No
Secondary	Correlation of cytogenetics and response		6, 12 mon then q 1 yr for 3 yrs post allo transpl	No