Melphalan and Stem Cell Transplant Before Total-Body Irradiation and Donor Stem Cell Transplant in Treating Patients With Stage I-III Multiple Myeloma

Refractory Multiple Myeloma Clinical Trial

Official title:

Allogeneic Stem Cell Transplantation For Multiple Myeloma: A Two Step Approach To Reduce Toxicity Involving High Dose Melphalan and Autologous Stem Cell Transplant Followed By PBSC Allografting After Low Dose TBI

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003954
• Other study ID #: 1383.00
• Secondary ID: NCI-2012-00670P0
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 1999

Study information

• Verified date: May 2019
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this study donor bone marrow transplantation is divided into a two step process to try to significantly reduce the side effects of the procedure yet still provide patients with multiple myeloma the benefits of this procedure

Description:

PRIMARY OBJECTIVES:

I. To evaluate engraftment of human leukocyte antigen (HLA) identical peripheral blood stem cell (PBSC) allografts given after conditioning with total-body irradiation (TBI) (200 cGy) and post-grafting immunosuppression with cyclosporine (CSP)/mycophenolate mofetil (MMF) in myeloma patients initially cytoreduced with high-dose melphalan.

II. To evaluate non-relapse mortality at day 100 post allografting. III. To evaluate the efficacy of this allografting strategy in terms of long-term progression free survival (PFS).

OUTLINE:

CONDITIONING REGIMEN: Patients receive high-dose melphalan intravenously (IV) over 15-20 minutes on day -2.

TRANSPLANTATION: Patients undergo autologous bone marrow or PBSC transplantation (PBSCT) on day 0.

NON-MYELOABLATIVE CONDITIONING REGIMEN: Beginning 40-120 days after autologous transplant, patients undergo TBI on day 0.

TRANSPLANTATION: Patients undergo donor PBSCT on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine IV twice daily (BID) on days -1 and 0 and orally (PO) BID on days 1-80 with taper based on evaluation of disease response and graft-versus-host disease (GVHD). Patients also receive mycophenolate mofetil PO BID on days 0-27.

POST-TRANSPLANTATION DONOR LYMPHOCYTE INFUSION (DLI): Beginning 4 weeks after immunosuppression, patients achieving persistent or progressive disease may undergo DLI over 30 minutes every 4 weeks for up to 3 treatments.

After completion of study treatment, patients are followed up for 3 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. primary completion date: December 2002
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 65 Years

Eligibility

Inclusion Criteria:

• Meet Salmon and Durie criteria for initial diagnosis of multiple myeloma; transplant will be offered to patients with stage II or III multiple myeloma (MM) at diagnosis or have received chemotherapy and/or radiation therapy for progressive MM after initial diagnosis of stage I disease

• The patient must have the capacity to give informed consent

• Have received at least 4 cycles of conventional dose chemotherapy for MM

• DONOR: HLA genotypically identical sibling

• DONOR: Donor must consent to filgrastim (G-CSF) administration and leukapheresis for both peripheral blood stem cell (PBSC) allograft and subsequent DLI

• DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian)

• DONOR: Age < 75, older donors may be considered after consultation by Psychological Consultation Center (PCC)

Exclusion Criteria:

• Karnofsky score less than 60, unless due solely to myeloma

• Left ventricular ejection fraction less than 40%

• Bilirubin greater than 2 X the upper limit of normal

• Serum glutamic pyruvic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) > 2 X the upper limit of normal

• Diffusion lung capacity of carbon monoxide (DLCO) < 50% (corrected) or receiving continuous supplemental oxygen

• Patients with poorly controlled hypertension

• Pregnancy

• Seropositive for the human immunodeficiency virus

• Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment

• Creatinine clearance < 40 cc/min at the time of initial autografting evaluation

• Prior autograft (can be treated on alternative protocol)

• DONOR: Identical twin

• DONOR: Age less than 12 years

• DONOR: Pregnancy

• DONOR: Infection with human immunodeficiency virus (HIV)

• DONOR: Inability to achieve adequate venous access

• DONOR: Known allergy to G-CSF

• DONOR: Current serious systemic illness

• DONOR: Failure to meet Fred Hutchinson Cancer Research Center (FHCRC) criteria for stem cell donation as described in the standard practice guidelines of the institution

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Refractory Multiple Myeloma
• Stage I Multiple Myeloma
• Stage II Multiple Myeloma
• Stage III Multiple Myeloma

Intervention

Drug:
• melphalan
Given IV

Procedure:
• autologous hematopoietic stem cell transplantation
Undergo autologous bone marrow or PBSCT
• autologous bone marrow transplantation
Undergo autologous bone marrow or PBSCT
• peripheral blood stem cell transplantation
Undergo autologous bone marrow or PBSCT

Radiation:
• total-body irradiation
Undergo TBI

Procedure:
• peripheral blood stem cell transplantation
Undergo donor PBSCT

Drug:
• cyclosporine
Given IV and PO
• mycophenolate mofetil
Given PO

Biological:
• therapeutic allogeneic lymphocytes
Undergo DLI

Locations

Country	Name	City	State
Italy	University of Torino	Torino
United States	University of Colorado	Denver	Colorado
United States	City of Hope	Duarte	California
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PFS	The current study will be regarded as potentially efficacious if the observed 3-year PFS rate among all patients treated exceeds 30%. The Kaplan-Meier (KM) estimate of PFS will be used.	From the date of transplant until the time of progression, relapse, death, or the date the patient was last known to be in remission, up to 3 years
Primary	Decrease in the short-term transplant-related mortality		Day 100 after allograft
Primary	Establish stable allogeneic engraftment (mixed or full donor chimerism)		At day 56 after allografting
Secondary	Overall survival	Estimated by the method of Kaplan and Meier. Confidence intervals will be estimated.	Up to 3 years
Secondary	Relapse rate	Summarized using cumulative incidence estimates. Confidence intervals will be estimated.	Up to 3 years
Secondary	Response rate	Confidence intervals will be estimated.	Up to 3 years
Secondary	Ability to convert mixed to full donor chimerism with DLI	Confidence intervals will be estimated.	Up to 3 years