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

January 4, 2023 updated by: Mayo Clinic

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

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 2
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: melphalan
Given IV
Other Names:
  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin
  • Melfalan
Drug: sirolimus
Given orally
Other Names:
  • Rapamune
  • AY 22989
  • rapamycin
  • SLM
  • RAPA
  • SILA 9268A
Drug: bortezomib
Given IV
Other Names:
  • MLN341
  • PS-341
  • LDP 341
  • VELCADE
Radiation: total-body irradiation
Undergo total-body irradiation
Other Names:
  • TBI
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
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Undergo transplantation
Drug: anti-thymocyte globulin
Given IV
Other Names:
  • ATGAM
  • ATG
  • Thymoglobulin
  • lymphocyte immune globulin
Drug: tacrolimus
Given oral or IV
Other Names:
  • Prograf
  • FK 506
  • Protopic
  • Advagraf

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Tolerability as assessed by CTCAE v3.0 (Phase I)
Assessment of toxicity (Phase I)
Proportion of successes
Transplant-related mortality (TRM) (Phase II)
Time Frame: 100 days
100 days
Rate acute graft-vs-host disease (GVHD) (Phase I)

Secondary Outcome Measures

Outcome Measure
Progression-free survival
Overall survival
Overall response
Rate of grades II-IV and grades III-IV acute graft-vs-host disease (GVHD)
Cumulative rate of chronic GVHD

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Investigators

  • Study Chair: Martha Q. Lacy, M.D., Mayo Clinic
  • Principal Investigator: James L. Slack, M.D., Mayo Clinic

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

First Submitted

October 12, 2009

First Submitted That Met QC Criteria

October 13, 2009

First Posted (Estimate)

October 14, 2009

Study Record Updates

Last Update Posted (Actual)

January 5, 2023

Last Update Submitted That Met QC Criteria

January 4, 2023

Last Verified

February 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MC078F (Other Identifier: Mayo Clinic Cancer Center)
  • NCI-2009-01249 (Registry Identifier: NCI-CTRP)
  • 08-003029 (Other Identifier: Mayo Clinic IRB)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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