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A Phase I/II Study of a Novel Reduced Intensity Conditioning Regimen for Allogeneic Stem Cell Transplantation in Patients With Multiple Myeloma

Phase 1/Phase 2
18 Years
Not Enrolling
Multiple Myeloma, Refractory Multiple Myeloma

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Trial Information

A Phase I/II Study of a Novel Reduced Intensity Conditioning Regimen for Allogeneic Stem Cell Transplantation in Patients With Multiple Myeloma


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.

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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Tolerability as assessed by CTCAE v3.0 (Phase I)

Safety Issue:


Principal Investigator

Martha Q. Lacy, M.D.

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

Completion Date:

Related Keywords:

  • Multiple Myeloma
  • Refractory Multiple Myeloma
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell