Peripheral Stem Cell Transplant in Treating Patients With Multiple Myeloma

NCT ID: NCT00028600

Last Updated: 2016-07-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-11-30
• Study Completion Date: 2010-02-28

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.

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.

Conditions

Multiple Myeloma; Plasma Cell Neoplasm

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Autologous + Allogeneic Transplant

autologous PB stem cell transplant followed by non-myeloablative allogeneic transplant fr multiple myeloma

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: BIOLOGICAL

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

Intervention Type: BIOLOGICAL

2-8,000,000/kg IV infusion allogeneic transplant 2,000,000/kg IV infusion autologous transplant

cyclophosphamide

Intervention Type: DRUG

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

Intervention Type: DRUG

30mg/sq m/d IVPB over 30 min d -7 thru -3 allo transpl

melphalan

Intervention Type: DRUG

200mg/sq m IV infusion over 15-30 min D 2 auto transpl

methotrexate

Intervention Type: DRUG

5mg/sq m/d IV infusion D 1,3,\& 6: allo transpl

tacrolimus

Intervention Type: DRUG

0.03mg/kg PO bid starting dose, D -1 thru +90, then taper thru D +150

Interventions

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

Intervention Type: BIOLOGICAL

CD34+ cells

2-8,000,000/kg IV infusion allogeneic transplant 2,000,000/kg IV infusion autologous transplant

Intervention Type: BIOLOGICAL

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

Intervention Type: DRUG

fludarabine phosphate

30mg/sq m/d IVPB over 30 min d -7 thru -3 allo transpl

Intervention Type: DRUG

melphalan

200mg/sq m IV infusion over 15-30 min D 2 auto transpl

Intervention Type: DRUG

methotrexate

5mg/sq m/d IV infusion D 1,3,\& 6: allo transpl

Intervention Type: DRUG

tacrolimus

0.03mg/kg PO bid starting dose, D -1 thru +90, then taper thru D +150

Intervention Type: DRUG

Other Intervention Names

G-CSF

Eligibility Criteria

Inclusion 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

• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kenneth C. Anderson, MD

Role: STUDY_CHAIR

Dana-Farber Cancer Institute

Locations

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Tunnell Cancer Center at Beebe Medical Center

Lewes, Delaware, United States

CCOP - Christiana Care Health Services

Newark, Delaware, United States

Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

Washington D.C., District of Columbia, United States

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, United States

Union Hospital Cancer Program at Union Hospital

Elkton MD, Maryland, 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 Township, New Jersey, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Mount Sinai Medical Center

New York, New York, United States

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Columbus, Ohio, United States

Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, United States

Countries

United States

References

Holstein SA, Suman VJ, Owzar K, Santo K, Benson DM Jr, Shea TC, Martin T, Silverman M, Isola L, Vij R, Cheson BD, Linker C, Anderson KC, Richardson PG, McCarthy PL. Long-Term Follow-up of CALGB (Alliance) 100001: Autologous Followed by Nonmyeloablative Allogeneic Transplant for Multiple Myeloma. Biol Blood Marrow Transplant. 2020 Aug;26(8):1414-1424. doi: 10.1016/j.bbmt.2020.03.028. Epub 2020 Apr 20.

Reference Type: DERIVED

PMID: 32325171 (View on PubMed)

Other Identifiers

U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CALGB-100001

Identifier Type: -

Identifier Source: secondary_id

CDR0000069109

Identifier Type: REGISTRY

Identifier Source: secondary_id

CALGB-100001

Identifier Type: -

Identifier Source: org_study_id