NCT01251172

Brief 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.

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Geographic Reach
1 country

1 active site

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 30, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 1, 2010

Completed
Same day until next milestone

Study Start

First participant enrolled

December 1, 2010

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2012

Completed
Last Updated

September 28, 2017

Status Verified

September 1, 2017

Enrollment Period

1.6 years

First QC Date

November 30, 2010

Last Update Submit

September 27, 2017

Conditions

Outcome Measures

Primary Outcomes (1)

  • Overall response rate of gamma-secretase/Notch signalling pathway inhibitor RO4929097 in eradicating residual/persistent disease, defined as conversion from VGPR to CR or sCR

    A Simon's 2-stage optimal Phase II design will be used to monitor the study.

    Up to 42 days

Secondary Outcomes (2)

  • Clonogenic myeloma progenitor cells

    At baseline, at 100 days post-transplant, and at 6 weeks

  • Incidence of adverse events and abnormal laboratory variables as assessed according to the NCI-CTCAE version 4.0

    Up to 30 days

Study Arms (1)

Treatment (RO4929097 after autologous stem cell transplant)

EXPERIMENTAL

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 (VGPR) continue to therapeutic treatment. THERAPEUTIC TREATMENT: Beginning 100-110 days after transplantation, patients receive oral gamma-secretase inhibitor 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.

Procedure: Autologous Hematopoietic Stem Cell TransplantationDrug: Gamma-Secretase Inhibitor RO4929097Procedure: Hematopoietic Stem Cell MobilizationProcedure: In Vitro-Treated Peripheral Blood Stem Cell TransplantationOther: Laboratory Biomarker AnalysisDrug: Melphalan

Interventions

Undergo in vitro treated autologous peripheral blood stem cell transplant

Also known as: Autologous Stem Cell Transplantation
Treatment (RO4929097 after autologous stem cell transplant)

Given orally

Also known as: RO4929097
Treatment (RO4929097 after autologous stem cell transplant)

Undergo standard mobilization

Treatment (RO4929097 after autologous stem cell transplant)

Undergo in vitro treated autologous peripheral blood stem cell transplant

Also known as: in vitro-treated PBPC transplantation, in vitro-treated peripheral blood progenitor cell transplantation
Treatment (RO4929097 after autologous stem cell transplant)

Correlative studies

Treatment (RO4929097 after autologous stem cell transplant)

Given IV

Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-Sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalanum, Phenylalanine Mustard, Phenylalanine Nitrogen Mustard, Sarcoclorin, Sarkolysin, WR-19813
Treatment (RO4929097 after autologous stem cell transplant)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients must have a diagnosis of multiple myeloma as defined below with staging based on the International Staging System:
  • Multiple myeloma - all three required (Note: these criteria identify stage 1B and stages II and IIIA/B myeloma by Durie/Salmon stage; stage 1A becomes smoldering or indolent myeloma):
  • Monoclonal plasma cells in the bone marrow ≥ 10% and/or presence of a biopsy-proven plasmacytoma
  • Monoclonal protein present in the serum and/or urine (if no monoclonal protein is detected \[non-secretory disease\], then \>= 30% monoclonal bone marrow plasma cells and/or biopsy-proven plasmacytoma is required)
  • Myeloma-related organ dysfunction (1 or more) (a variety of other types of end organ dysfunctions can occasionally occur and lead to a need for therapy; such dysfunction is sufficient to support classification as myeloma if proven to be myeloma related):
  • Calcium elevation in the blood (serum calcium \> 10.5 mg/L or upper limit of normal)
  • Renal insufficiency (serum creatinine \> 2mg/dL)
  • Anemia (hemoglobin \< 10 g/dL or 2 g \< normal)
  • Lytic bone lesions or osteoporosis (if a solitary \[biopsy-proven\] plasmacytoma or osteoporosis alone \[without fractures\] are the sole defining criteria, then \> 30% plasma cells are required in the bone marrow)
  • Patients must have measurable disease
  • Patients with non-secretory multiple myeloma will be eligible only if the baseline serum free light chain level is elevated (\>= 10 mg/dL)
  • For therapeutic treatment with RO4929097, patients must have peripheral blood stem cell collection of \>= 4.0 x 10\^6 cells/kg (patient's ideal body weight)
  • ECOG performance status =\< 2, Karnofsky \>= 60%
  • Estimated life expectancy of at least 12 weeks
  • Absolute neutrophil count (ANC) \>= 1,500/mcL
  • +39 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

2,2-dimethyl-N-(6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-N'-(2,2,3,3,3-pentafluoropropyl)malonamideHematopoietic Stem Cell MobilizationMelphalan

Condition Hierarchy (Ancestors)

Neoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Biological TherapyTherapeuticsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhenylalanineAmino Acids, AromaticAmino Acids, CyclicAmino AcidsAmino Acids, Peptides, and Proteins

Study Officials

  • Mecide Gharibo

    Rutgers Cancer Institute of New Jersey

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 30, 2010

First Posted

December 1, 2010

Study Start

December 1, 2010

Primary Completion

July 1, 2012

Last Updated

September 28, 2017

Record last verified: 2017-09

Locations