2nd Autologous Stem Cell Transplant in Patients With Persistent/Recurrent (AL) Amyloidosis

Phase II Trial of Second Autologous Transplantation in AL Amyloidosis

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of plasma cells, either by killing the cells or by stopping them from dividing. Having a stem cell transplant to replace the blood-forming cells destroyed by chemotherapy, allows higher doses of chemotherapy to be given so that more plasma cells are killed. By reducing the number of plasma cells, the disease may progress more slowly.

PURPOSE: This phase II trial is studying how well autologous stem cell transplant works in treating patients with persistent or recurrent primary systemic (AL) amyloidosis.

Study Overview

• Status: Terminated
• Conditions: Multiple Myeloma; Plasma Cell Neoplasm
• Intervention / Treatment: Biological: filgrastim; Drug: melphalan; Procedure: autologous stem cell transplantation; Procedure: stem cell infusion

Detailed Description

OBJECTIVES:

• Determine the feasibility and tolerability of second autologous stem cell transplantation in patients with persistent or recurrent AL amyloidosis.
• Determine the response rate and durability of response in patients treated with this regimen.
• Determine immune reconstitution in patients treated with this regimen.

OUTLINE:

• Mobilization: Patients receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning before the initiation of stem cell collection and continuing until the day before the completion of stem cell collection.
• Preparative regimen: Patients receive high-dose melphalan IV over 20 minutes on days -3 and -2.
• Autologous stem cell transplantation: Autologous stem cells are reinfused on day 0.

Patients are followed at 6 months, 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 19 patients will be accrued for this study within 5-6 years.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

DISEASE CHARACTERISTICS:

• Histologically confirmed AL amyloidosis

  • Persistent or recurrent disease after 1 course of prior high-dose chemotherapy
• Previously treated with autologous stem cell transplantation

• Significant initial improvement in organ function after prior high-dose melphalan, defined by at least 1 of the following:

  • Complete hematologic remission (e.g., absence of monoclonal spike by immunofixation in serum and urine AND less then 5% plasma cells in bone marrow with no clonal predominance) OR partial hematologic response (e.g., any decrease in serum or urine monoclonal protein OR decrease in bone marrow plasmacytosis)
  • Greater than 50% reduction in proteinuria with preservation of creatinine clearance
  • Greater than 50% reduction in alkaline phosphatase OR at least 2 cm decrease in liver size by physical exam
  • Subjective neurologic improvement, as confirmed by neurologist
  • Cardiac stabilization of disease confirmed by echocardiography defined as less than 2 mm increase in mean wall thickness and/or less than 20 g increase in left ventricular mass
  • Improvement in performance status* NOTE: *This criteria alone does not constitute significant improvement in organ function
• Prior stem cell yield must have been ≥ 2 x 10^6 CD34+ cells/kg

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• See Disease Characteristics
• No chemotherapy after first transplantation

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

PATIENT CHARACTERISTICS:

Age

• 18 to 65

Performance status

• Southwest Oncology Group- 0-2

Life expectancy

• More than 6 months

Hematopoietic

• See Disease Characteristics

Hepatic

• See Disease Characteristics

Renal

• See Disease Characteristics

Cardiovascular

• See Disease Characteristics
• Left ventricular ejection fraction ≥ 45% by multiple gated acquisition scan or echocardiogram

Pulmonary

• diffusing capacity of lung for carbon monoxide ≥ 50%

Exclusion Criteria:

• No myelodysplastic syndromes
• No abnormal bone marrow cytogenetics

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• Acceptable toxicity from first transplantation, confirmed by the transplant team
• HIV negative
• No other concurrent malignancy except treated skin cancer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 2nd Stem Cell Transplant; Mobilization with filgrastim autologous stem cell transplantation with melphalan conditioning stem cell infusion

Biological: filgrastim; 16mcg/kg IV daily beginning three days prior to stem cell collection through last day of stem cell collection; Other Names: G-CSF; Drug: melphalan; 140-200 mcg/kg IV over two days; Other Names: alkeran; Procedure: autologous stem cell transplantation; infusion of previously collected stem cells on Day 0; Procedure: stem cell infusion; infusion of previously collected stem cells on Day 0

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility and Tolerability	Feasibility and tolerability will be evaluated based on participants completing second transplant with tolerable adverse events	3 months after treatment and annually
Response and Durability of Response	Response and durability of response will be based on hematologic Complete Response or Partial Response and date of relapse or death	3 months after treatment and annually
Evaluate Immune Reconstitution	Evaluate immune reconstitution based on time to engraftment	3 months after treatment and annually

Collaborators and Investigators

• Sponsor: Boston Medical Center
• Investigators: Principal Investigator: Karen Quillen, MD, Boston Medical Center

Study record dates

Study Major Dates

• Study Start: August 1, 2001
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: January 9, 2004
• First Submitted That Met QC Criteria: January 11, 2004
• First Posted (Estimate): January 12, 2004

Study Record Updates

• Last Update Posted (Estimate): January 27, 2017
• Last Update Submitted That Met QC Criteria: December 2, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: primary systemic amyloidosis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Proteostasis Deficiencies; Multiple Myeloma; Neoplasms, Plasma Cell; Amyloidosis; Plasmacytoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Melphalan
• Other Study ID Numbers: CDR0000347379; H-22603 (Other Identifier: Boston University Medical Center IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No