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

NCT00995059 | Withdrawn Phase 1 DMC

• 3 other identifiers: MC078FNCI-2009-0124908-003029
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Multiple Myeloma; Refractory Multiple Myeloma

Keywords

stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma

Outcome Measures

Primary Outcomes (5)

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

• Assessment of toxicity (Phase I)

• Proportion of successes

• Transplant-related mortality (TRM) (Phase II)

  100 days

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

Secondary Outcomes (5)

• 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

Study Arms (1)

Arm 1

EXPERIMENTAL

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; Procedure: allogeneic bone marrow transplantation; Drug: bortezomib; Drug: melphalan; Drug: anti-thymocyte globulin; Drug: sirolimus; Drug: tacrolimus; Radiation: total-body irradiation

Interventions

nonmyeloablative allogeneic hematopoietic stem cell transplantation PROCEDURE

Undergo transplantation

Arm 1

allogeneic bone marrow transplantation PROCEDURE

Undergo transplantation

Also known as: bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow

Arm 1

bortezomib DRUG

Given IV

Also known as: LDP 341, MLN341, PS-341, VELCADE

Arm 1

melphalan DRUG

Given IV

Also known as: Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin, Melfalan

Arm 1

anti-thymocyte globulin DRUG

Given IV

Also known as: ATG, ATGAM, lymphocyte immune globulin, Thymoglobulin

Arm 1

sirolimus DRUG

Given orally

Also known as: AY 22989, RAPA, Rapamune, rapamycin, SILA 9268A, SLM

Arm 1

tacrolimus DRUG

Given oral or IV

Also known as: Advagraf, FK 506, Prograf, Protopic

Arm 1

total-body irradiation RADIATION

Undergo total-body irradiation

Also known as: TBI

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Transplantation; Bortezomib; Melphalan; Antilymphocyte Serum; thymoglobulin; Sirolimus; Tacrolimus; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Macrolides; Lactones; Radiotherapy; Therapeutics; Investigative Techniques

Study Officials

• Martha Q. Lacy, M.D.

  Mayo Clinic

  STUDY CHAIR

• James L. Slack, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2009
• First Posted: October 14, 2009
• Last Updated: January 5, 2023

Record last verified: 2011-02