Clinical trial NCT01534143
Conditions: Refractory Multiple Myeloma Stage I Multiple Myeloma Stage II Multiple Myeloma Stage III Multiple Myeloma
Sponsor: Barbara Ann Karmanos Cancer Institute
Start date: 2012-02-01; Completion date: 2013-05-01
Enrollment: 1 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This pilot phase II trial studies how well giving high dose busulfan together with bortezomib works in treating patients with high risk multiple myeloma undergoing stem cell transplant. Drugs used in chemotherapy, such as busulfan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cells growth. Giving busulfan together with bortezomib before a stem cell transplant may kill more cancer cells

Detailed description:
PRIMARY OBJECTIVES:

I. To determine time to engraftment absolute neutrophil count (\> 0.5 x 10\^9/L for 3 consecutive days), and platelet (\> 20X 109\^/L for 3 consecutive days).

2\. Incidence and severity of acute graft-versus-host disease (GVHD) using fludarabine (fludarabine phosphate) / busulfan / bortezomib preparative regimen and triple immune suppression with tacrolimus, sirolimus and Thymoglobulin (anti-thymocyte globulin).

3\. To determine the safety related to this combination in the first six months post transplant, specifically, treatment related mortality and grade III and IV non hematologic toxicities, based on Common Terminology Criteria for Adverse Events (CTCAE) version 4 (v4).

SECONDARY OBJECTIVES:

I. Incidence of myeloma progression in this high risk group of patients.

II. Incidence of transplant related mortality and morbidity.

III. Incidence of thrombotic thrombocytopenic purpura (TTP) and sinusoidal obstructive syndrome (SOS).

IV. Incidence and severity of chronic GVHD.

V. Incidence of opportunistic infections including cytomegalovirus (CMV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV) reactivation.

I. Overall and progression free survival (PFS) at Day 100, 6 months, 1 \& 2 years post transplant.

VII. To determine recovery of T-cell, B cell, and natural killer (NK) cell phenotypes post transplant.

OUTLINE:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -7 to -3, busulfan IV on days -6 to -3, and bortezomib IV on day -2.

GVHD PROPHYLAXIS: Patients receive anti-thymocyte globulin IV on days -3 to -1, sirolimus orally (PO) on day -3, and tacrolimus IV on day -3. Patients undergo allogeneic hematopoietic stem cell transplantation (HSCT) on day 0.

After completion of study treatment, patients are followed up for up to 2 years.

Arms: arm 1: CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -7 to -3, busulfan IV on days -6 to -3, and bortezomib IV on day -2.

GVHD PROPHYLAXIS: Patients receive thymoglobulin IV on days -3 to -1, sirolimus PO on day -3, and tacrolimus IV on day -3. Patients undergo allogeneic HSCT on day 0.
Interventions: intervention 1: pharmacological study intervention 2: tacrolimus intervention 3: sirolimus intervention 4: anti-thymocyte globulin intervention 5: fludarabine phosphate intervention 6: busulfan intervention 7: bortezomib intervention 8: allogeneic hematopoietic stem cell transplantation intervention 9: laboratory biomarker analysis
Intervention descriptions: intervention 1: Correlative studies intervention 2: Given IV intervention 3: Given PO intervention 4: Given IV intervention 5: Given IV intervention 6: Given IV intervention 7: Given IV intervention 8: Undergo allogeneic HSCT intervention 9: Correlative studies

Protocol documents: