Trial record 13 of 524 for:    Open Studies | "Multiple Myeloma"

Bortezomib, Total Marrow Irradiation, Fludarabine Phosphate, and Melphalan in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant For High-Risk Stage I or II Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by City of Hope Medical Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT01163357
First received: July 14, 2010
Last updated: May 6, 2014
Last verified: May 2014
  Purpose

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving chemotherapy drugs, such as fludarabine phosphate and melphalan, and total marrow irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with fludarabine phosphate and melphalan with or without total marrow irradiation in treating patients undergoing donor peripheral blood stem cell transplant for high-risk stage I or II multiple myeloma.


Condition Intervention Phase
Refractory Multiple Myeloma
Stage I Multiple Myeloma
Stage II Multiple Myeloma
Drug: bortezomib
Drug: fludarabine phosphate
Other: melphalan
Radiation: total marrow irradiation
Drug: tacrolimus
Drug: sirolimus
Procedure: peripheral blood stem cell transplantation
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Bortezomib With or Without Total Marrow Irradiation (TMI) Using Intensity Modulated Radiation Therapy (IMRT) in Combination With Fludarabine (FLU) and Melphalan (MEL) as a Preparative Regimen for Allogeneic Hematopoietic Stem Cell (HSC) Transplantation in Patients With High Risk Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Maximum tolerated dose of bortezomib as defined as the highest dose tested in which none or only one patient experiences dose limiting toxicity attributable to the study regimen [ Time Frame: 6 weeks post transplant ] [ Designated as safety issue: Yes ]
    Assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Dose-limiting toxicity will be defined using Bearman Scale for events that occur.

  • Feasibility of escalating doses of bortezomib with or without TMI in combination with FLU and MEL as preparative regimen for allogeneic hematopoietic stem cell transplant in patients with high risk multiple myeloma [ Time Frame: 5 years post transplant ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Frequency of clinical response (i.e., complete, partial, or very good partial response) [ Time Frame: At 6 months and 1 year post transplant ] [ Designated as safety issue: No ]
    Response is evaluated based on a new International myeloma working group uniform response criteria.

  • Frequency of primary and secondary engraftment failure [ Time Frame: 6 weeks post transplant ] [ Designated as safety issue: No ]
  • Time to neutrophil and platelet engraftment [ Time Frame: 100 days post transplant ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: 4 years post transplant ] [ Designated as safety issue: No ]
    Time from day 0 of transplant to the first observation or relapse or death due to any cause, assessed up to 4 years

  • Incidence of acute and chronic graft-versus-host disease [ Time Frame: At 6 months and 1 year post transplant up to 4 years post transplant ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 4 years post transplant ] [ Designated as safety issue: No ]
    Time from first day of treatment to time of death due to any cause, assessed up to 4 years

  • Minimal residue disease [ Time Frame: At 6 months and 1 year post transplant ] [ Designated as safety issue: No ]

Estimated Enrollment: 27
Study Start Date: January 2011
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group I (bortezomib, fludarabine phosphate, TMI, melphalan)
Patients receive bortezomib IV on days -6 and -3 and undergo TMI BID on days -9 to -7. Patients also receive fludarabine phosphate IV on days -9 to -5 and melphalan IV on day -4.
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • PS-341
  • VELCADE
Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Other: melphalan
Given IV
Other Names:
  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin
  • Melfalan
Radiation: total marrow irradiation
Undergo TMI
Drug: tacrolimus
Given IV and orally
Other Names:
  • Advagraf
  • FK 506
  • Prograf
  • Protopic
Drug: sirolimus
Given orally
Other Names:
  • AY 22989
  • RAPA
  • Rapamune
  • rapamycin
  • SILA 9268A
  • SLM
Procedure: peripheral blood stem cell transplantation
Undergo allogeneic PBSC transplant
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Other: laboratory biomarker analysis
Correlative studies
Experimental: Group II (bortezomib, fludarabine phosphate, melphalan
Patients receive bortezomib IV on days -6, -3, 1, and 4. Patients also receive fludarabine phosphate IV and melphalan IV as in Group I.
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • PS-341
  • VELCADE
Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Other: melphalan
Given IV
Other Names:
  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin
  • Melfalan
Drug: tacrolimus
Given IV and orally
Other Names:
  • Advagraf
  • FK 506
  • Prograf
  • Protopic
Drug: sirolimus
Given orally
Other Names:
  • AY 22989
  • RAPA
  • Rapamune
  • rapamycin
  • SILA 9268A
  • SLM
Procedure: peripheral blood stem cell transplantation
Undergo allogeneic PBSC transplant
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the feasibility of escalating doses of bortezomib with or without total marrow irradiation (TMI) at a fixed dose of 900 cGy in combination with fludarabine (FLU) and melphalan (MEL) as preparative regimen for allogeneic hematopoietic stem cell transplant in patients with high risk multiple myeloma who have human leukocyte antigen (HLA) matched donor (sibling or matched unrelated donor).

II. To describe toxicities, maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of this preparative regimen.

SECONDARY OBJECTIVES:

I. To evaluate the frequency of clinical response, i.e., complete response [CR], partial response [PR], very good partial response [VGPR]) at 6 month and 1 year post transplant.

II. To evaluate the frequency of primary and secondary engraftment failure.

III. To evaluate the time to neutrophil and platelet engraftment.

IV. To evaluate the incidence of acute and chronic graft-versus-host disease (GVHD).

V. To evaluate progression-free survival.

VI. To evaluate overall survival.

VII. To evaluate minimal residual disease (MRD) at 6 months and 1 year post transplant by flow cytometry in the bone marrow.

OUTLINE: This is a dose-escalation study of bortezomib. Patients are assigned to 1 of 2 treatment groups. GROUP I (patients eligible for TMI): Patients receive bortezomib intravenously (IV) on days -6 and -3 and undergo TMI twice daily (BID) on days -9 to -7. Patients also receive fludarabine phosphate IV on days -9 to -5 and melphalan IV on day -4. GROUP II (patients ineligible for TMI): Patients receive bortezomib IV on days -6, -3, 1, and 4. Patients also receive fludarabine phosphate IV and melphalan IV as in Group I.

TRANSPLANT: All patients undergo allogeneic peripheral blood stem cell (PBSC) transplant on day 0.

GVHD PROPHYLAXIS: All patients receive tacrolimus IV or orally (PO) and sirolimus PO beginning on day -3.

After completion of study treatment, patients are followed up at day 100, 6 months, and then annually thereafter.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Recipient must have signed a voluntary, informed consent in accordance with institutional and federal guidelines
  • Recipients must have histopathologically confirmed diagnosis of multiple myeloma
  • Age:

    • Stratum I (TMI containing arm): 18-60 years of age
    • Stratum II (non TMI arm): 18-70 years of age
  • Patients with primary progressive disease on induction therapy with new targeted therapies
  • Relapsed/refractory disease on new targeted therapies, i.e. thalidomide, lenalidomide, bortezomib, or other new novel agents such as carfilzomib, pomalidomide
  • Patients with relapsed multiple myeloma following previous autologous stem cell transplant
  • Plasma cell leukemia at diagnosis
  • High-risk patients with presence of chromosome 17p deletion (> 60%) in the bone marrow by fluorescence in situ hybridization (FISH); patients are not required to have prior autologous stem cell transplant
  • Able to lie supine for approximately 60 minutes, the anticipated duration of each treatment session
  • Performance status evaluated by Eastern Cooperative Oncology Group (ECOG) or Karnofsky Performance Scales (KPS) patients must have a score of 0-II (ECOG) or >= 70% (KPS)
  • Cardiac ejection fraction >= 50% by multiple gate acquisition (MUGA) scan and/or by echocardiogram
  • Forced expiratory volume in one second (FEV1) >= 50%
  • Diffusing lung capacity for carbon monoxide (DLCO) >= 50%
  • Creatinine clearance or glomerular filtration rate (GFR) >= 60 ml/min
  • Serum bilirubin =< 2.0 mg/dl
  • Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) =< 2.5 times the institutional upper limits of normal
  • Pre-treatment tests must be performed within 30 days prior to enrollment
  • No other medical and or psychosocial problems, which in the opinion of the primary physician or principal investigator would place the patient at unacceptable risk from this regimen
  • Patients with no previous radiation or up to a maximum 2000 cGy to non thoracic-spine and rib bone lesions or < 20% of bone marrow are eligible for TMI conditioning regimen
  • Patients with previous history of irradiation at any dose to thoracic-spine, ribs or >= 20% of bone marrow cannot undergo TMI and will be eligible for bortezomib, fludarabine, and melphalan regimen

Stratum II); patients can be enrolled on stratum II at their physician's discretion or if patients decline radiation therapy

DONOR: Any matched sibling donor (matched at HLA A, B, C by intermediate resolution typing and HLA-DRB1 by high resolution typing), or unmatched unrelated donor (matched at HLA A, B, C, DRB1 by high resolution typing) will be considered a suitable donor

Exclusion Criteria:

  • Patients with peripheral neuropathy greater than grade II
  • Major medical or psychiatric disorders that would seriously compromise patient tolerance of this regimen
  • Human immunodeficiency virus (HIV) infection, active hepatitis B or C infection, or evidence of liver cirrhosis
  • Active viral, bacterial or fungal infection unless adequately treated. For fungal infection, patient should have completed full course of antifungal therapy with resolution of infection.
  • Patients with radiographic changes including pulmonary disease, including but not limited to: pulmonary nodules, infiltrates, pleural effusion are excluded unless cleared by pulmonary biopsy showing no evidence for pulmonary infection
  • Patients with renal insufficiency or cr clearance < 60 ml/min

DONOR: Donors will be excluded if for medical or psychological reasons they are unable to tolerate the procedure of peripheral stem cell donation

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01163357

Locations
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Firoozeh Sahebi, MD    800-826-4673    fsahebi@coh.org   
Principal Investigator: Firoozeh Sahebi, MD         
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Firoozeh Sahebi, MD Beckman Research Institute
  More Information

No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT01163357     History of Changes
Other Study ID Numbers: 09171, NCI-2010-01610
Study First Received: July 14, 2010
Last Updated: May 6, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Melphalan
Fludarabine
Fludarabine phosphate
Bortezomib
Sirolimus
Tacrolimus
Vidarabine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on August 20, 2014