RO4929097 After Autologous Stem Cell Transplant in Treating Patients With Multiple Myeloma

Refractory Plasma Cell Myeloma Clinical Trial

Official title: Phase II Study of RO4929097 to Eradicate Residual Disease in Patients With Multiple Myeloma Post Single Autologous Stem Cell Transplant

Status Withdrawn

Clinical Trial Summary

This phase II clinical trial is studying how well gamma-secretase/Notch signalling pathway inhibitor RO4929097 (RO4929097) after autologous stem cell transplant works in treating patients with multiple myeloma. Giving chemotherapy, such as melphalan, before autologous stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Before treatment, stem cells are collected from the patient's blood and stored. After chemotherapy, the stem cells are returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. RO4929097 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving RO4929097 after autologous stem cell transplant may kill more cancer cells.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the efficacy of RO4929097 in eradicating residual/persistent disease (conversion of VGPR to CR or sCR status) in multiple myeloma patients status post single high-dose melphalan/autologous stem cell rescue with residual/persistent disease post-transplant.

SECONDARY OBJECTIVES:

I. To determine the safety of single agent RO4929097 post-autologous stem cell transplant in multiple myeloma patients.

II. To analyze Notch receptor and ligand protein expression in pre-transplant, pre-treatment with RO4929097, and post-treatment bone marrow biopsy samples.

III. To isolate and identify clonogenic multiple myeloma progenitor cells from bone marrow aspirate and/or peripheral blood at the following time points: pre-transplant, day 100 post-transplant, and post-treatment staging bone marrow biopsy.

IV. To analyze Notch receptor and ligand protein expression on isolated clonogenic progenitor myeloma cells.

V. To characterize the tumor xenograft-initiating potential of clonogenic myeloma cells in adult Casper zebrafish and SCID-hu model and evaluate the drug toxicity and therapeutic potential of RO4929097 with this model.

VI. To analyze anti-angiogenic effects of RO4929097 as measured by reduction in microvessel density and VEGFR-1 expression in pre-treatment and post-treatment bone marrow biopsy samples.

VII. To determine whether measurement of soluble surrogate markers of angiogenesis prior to and following treatment with RO4929097 provide an early marker of disease response to Notch inhibition.

OUTLINE: This is a multicenter study.

STEM CELL TRANSPLANTATION AND CHEMOTHERAPY: Patients undergo standard mobilization and collection of autologous peripheral stem cells (>= 4.0 x 10^6 CD34+ cells/kg). Patients then receive high-dose melphalan IV on days -3 and -2 and undergo autologous stem cell transfusion on day 0. Patients with progressive disease, stable disease, partial response, stringent complete response, or complete response are taken off study; patients with residual/persistent disease (very good partial response [VGPR]*) continue to therapeutic treatment.

NOTE: *Patients who meet the criteria for VGPR but have findings of abnormal bone marrow cytogenetic study demonstrating >= 10% metaphase cells positive for either high-risk chromosomal abnormalities or persistent disease-related chromosomal abnormalities (e.g., chromosome del 13; del17p, t(4;14), t(14;16), t(6;14) or complex cytogenetics) will have a repeat bone marrow biopsy assessment with cytogenetics within 2-3 weeks. If the repeat biopsy findings suggest persistent high-risk cytogenetic findings, then the patient is considered eligible to receive RO4929097 to eradicate residual disease.

THERAPEUTIC TREATMENT: Beginning 100-110 days after transplantation, patients receive oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for at least 4 weeks. ;

Related Conditions & MeSH terms

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

• NCT number: NCT01251172
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Withdrawn
• Phase: Phase 2
• Start date: December 2010