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

Information source: Mayo Clinic
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Multiple Myeloma; Refractory Multiple Myeloma

Intervention: nonmyeloablative allogeneic hematopoietic stem cell transplantation (Procedure); allogeneic bone marrow transplantation (Procedure); bortezomib (Drug); melphalan (Drug); anti-thymocyte globulin (Drug); sirolimus (Drug); tacrolimus (Drug); total-body irradiation (Radiation)

Phase: Phase 1/Phase 2

Status: Withdrawn

Sponsored by: Mayo Clinic

Official(s) and/or principal investigator(s):
Martha Q. Lacy, M.D., Study Chair, Affiliation: Mayo Clinic
James L. Slack, M.D., Principal Investigator, Affiliation: Mayo Clinic in Arizona


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.

Clinical Details

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

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

Primary outcome:

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

Assessment of toxicity (Phase I)

Proportion of successes

Transplant-related mortality (TRM) (Phase II)

Rate acute graft-vs-host disease (GVHD) (Phase I)

Secondary outcome:

Rate of grades II-IV and grades III-IV acute graft-vs-host disease (GVHD)

Cumulative rate of chronic GVHD

Overall response

Overall survival

Progression-free survival

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.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.


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


- 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

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Last updated: February 4, 2011

Page last updated: August 23, 2015

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