Clinical trial NCT00028600: Peripheral Stem Cell Transplant in Treating Patients With Multiple Myeloma
Official title: Autologous Followed By Non-Myeloablative Allogeneic Transplant For Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Plasma Cell Neoplasm
Keywords: refractory multiple myeloma
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 60
Sex: ALL
Maximum age (years): 64
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Treatment-related mortality
timeFrame: 6 months
Secondary outcomes:
measure: Treatment Completion Rate
timeFrame: post treatment
measure: Respone Rate
timeFrame: 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
measure: Chimerism Rate
timeFrame: 1,2,3,4, & 6 mon post allo transpl, & 100 d post DLI
measure: GVHD Incidence
timeFrame: post allo transpl, & pre & post DLI
measure: Survival
timeFrame: 2 years
measure: Correlation of cytogenetics and response
timeFrame: 6, 12 mon then q 1 yr for 3 yrs post allo transpl
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Lewes
country: United States
facility: Tunnell Cancer Center at Beebe Medical Center
state: Delaware
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Washington
country: United States
facility: Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
state: District of Columbia
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Elkton MD
country: United States
facility: Union Hospital Cancer Program at Union Hospital
state: Maryland
city: St Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - Saint Louis
state: Missouri
city: Voorhees
country: United States
facility: Cancer Institute of New Jersey at Cooper - Voorhees
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
state: Pennsylvania
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Kenneth C. Anderson, MD
role: STUDY_CHAIR
References:
citation: 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.