Bortezomib Before Donor Stem Cell Transplant in Treating Patients With Multiple Myeloma

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00995059
First received: October 12, 2009
Last updated: February 4, 2011
Last verified: February 2011
  Purpose

Rationale: Giving bortezomib and low doses of chemotherapy and total-body irradiation before a donor stem cell transplant or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving sirolimus and tacrolimus before and after transplant may stop this from happening.

Purpose: This phase I/II trial is studying the side effects and best dose of bortezomib before donor stem cell transplant in treating patients with multiple myeloma.


Condition Intervention Phase
Multiple Myeloma
Refractory Multiple Myeloma
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Procedure: allogeneic bone marrow transplantation
Drug: bortezomib
Drug: melphalan
Drug: anti-thymocyte globulin
Drug: sirolimus
Drug: tacrolimus
Radiation: total-body irradiation
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of a Novel Reduced Intensity Conditioning Regimen for Allogeneic Stem Cell Transplantation in Patients With Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Tolerability as assessed by CTCAE v3.0 (Phase I) [ Designated as safety issue: Yes ]
  • Assessment of toxicity (Phase I) [ Designated as safety issue: Yes ]
  • Proportion of successes [ Designated as safety issue: No ]
  • Transplant-related mortality (TRM) (Phase II) [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
  • Rate acute graft-vs-host disease (GVHD) (Phase I) [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Rate of grades II-IV and grades III-IV acute graft-vs-host disease (GVHD) [ Designated as safety issue: Yes ]
  • Cumulative rate of chronic GVHD [ Designated as safety issue: Yes ]
  • Overall response [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]

Estimated Enrollment: 34
Arms Assigned Interventions
Experimental: Arm 1
CONDITIONING: Patients receive bortezomib IV and then undergo fractionated total-body irradiation on days -5 and -2. Patients receive thymoglobulin IV over 6 hours on days -5 to -2 and melphalan IV over 30 minutes on days -4 to -3. ALLOGENEIC STEM CELL TRANSPLANTATION: Patients undergo bone marrow or peripheral blood stem cell transplant on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Beginning on day -3, patients receive oral sirolimus and taper beginning on day 61. Beginning on day -2, patients receive oral or IV tacrolimus and taper beginning on day 101.
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Undergo transplantation
Procedure: allogeneic bone marrow transplantation
Undergo transplantation
Other Names:
  • bone marrow therapy, allogeneic
  • bone marrow therapy, allogenic
  • transplantation, allogeneic bone marrow
  • transplantation, allogenic bone marrow
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • PS-341
  • VELCADE
Drug: melphalan
Given IV
Other Names:
  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin
  • Melfalan
Drug: anti-thymocyte globulin
Given IV
Other Names:
  • ATG
  • ATGAM
  • lymphocyte immune globulin
  • Thymoglobulin
Drug: sirolimus
Given orally
Other Names:
  • AY 22989
  • RAPA
  • Rapamune
  • rapamycin
  • SILA 9268A
  • SLM
Drug: tacrolimus
Given oral or IV
Other Names:
  • Advagraf
  • FK 506
  • Prograf
  • Protopic
Radiation: total-body irradiation
Undergo total-body irradiation
Other Name: TBI

Detailed Description:

Objectives:

I. To determine the maximum tolerated dose (MTD) of bortezomib when used in a novel conditioning regimen for patients undergoing allogeneic stem cell transplantation for multiple myeloma.

II. To evaluate the tolerability and feasibility of this novel conditioning regimen and GVHD prophylaxis strategy incorporating several anti-myeloma agents, including bortezomib, in patients undergoing allogeneic stem cell transplantation for multiple myeloma.

III. To obtain an initial assessment of the efficacy of this novel conditioning regimen.

Outline: This is a phase I dose-escalation study of bortezomib followed by a phase II study.

Reduced-Intensity Conditioning: Patients receive bortezomib IV and then undergo fractionated total-body irradiation on days -5 and -2. Patients receive thymoglobulin IV over 6 hours on days -5 to -2 and melphalan IV over 30 minutes on days -4 to -3.

Allogenic Stem Cell Transplantation: Patients undergo bone marrow or peripheral blood stem cell transplant on day 0.

Graft versus Host Disease Prophylaxis: Beginning on day -3, patients receive oral sirolimus and taper beginning on day 61. Beginning on day -2, patients receive oral or IV tacrolimus and taper beginning on day 101. After completion of the study treatment, patients are followed every 3 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ECOG performance status (PS) 0, 1, or 2
  • Diagnosis of symptomatic multiple myeloma
  • High risk myeloma as defined by progressive disease =< 12 months after high dose chemotherapy and autologous HSC transplant or presences of poor prognostic features such as deletion of chromosome 13 or hypodiploidy by standard cytogenetics, or t(4; 14) by fluorescence in situ hybridization (FISH), or t(14;16) by FISH, or 17p- by FISH, or plasma cell labeling index >= 3%
  • Availability of a HLA fully-matched or 1 mismatch related donor by low-resolution HLA typing for the loci A, B, C, DRB1 and DQB1 or HLA fully-matched unrelated donor by high-resolution typing for loci A, B, C and DRB1 and at least low-resolution for loci DQB1
  • Recovery from toxicity of previous chemotherapy (excludes grade 1 neurotoxicity and hematological toxicity)
  • Physically and psychologically capable of undergoing bone marrow or PBSC transplant
  • Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
  • Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control for the during of the study
  • Male subject agrees to use an acceptable method for contraception for the duration of the study

Exclusion Criteria:

  • Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV hear failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • NOTE: Prior to study entry, and ECG abnormality at screening has to be documented by the investigator as not medically relevant
  • Significant cardiac dysfunction defined as left ventricle ejection fraction < 40% or presence of symptomatic coronary artery disease
  • Significant pulmonary disease defined as FEV < 50% or CLCO < 50% of the predicted values
  • Pre existing peripheral neuropathy grade > 1
  • Significant renal dysfunction defined as estimated creatinine clearance < 50 ml/min
  • Significant liver dysfunction defined as total bilirubin >= 2 x upper limit of normal (ULN) or AST, ALT >= 3 x ULN
  • Seroreactive for HIV, HTLV I or II, HBV, HCV
  • Presence of uncontrolled bacterial, viral, or fungal infection
  • Known allergy to any of the component of the investigational treatment regimen or required ancillary treatments
  • Considered unable to tolerate the included doses of total body irradiation due to previous treatment with radiation
  • Female subject is pregnant or breast-feeding
  • Other active concurrent malignancy
  • Prior allogeneic bone marrow/peripheral blood stem cell transplant
  • Received other investigational drugs =< 14 days prior to enrollment
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00995059

Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Martha Q. Lacy, M.D. Mayo Clinic
Principal Investigator: James L. Slack, M.D. Mayo Clinic in Arizona
  More Information

No publications provided

Responsible Party: Martha Q. Lacy, M.D., Mayo Clinic Cancer Center
ClinicalTrials.gov Identifier: NCT00995059     History of Changes
Other Study ID Numbers: MC078F, NCI-2009-01249, 08-003029, MC078F
Study First Received: October 12, 2009
Last Updated: February 4, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

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
Antilymphocyte Serum
Melphalan
Sirolimus
Everolimus
Tacrolimus
Immunoglobulins
Bortezomib
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Myeloablative Agonists
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on April 17, 2014