Combination Plerixafor (AMD3100)and Bortezomib in Relapsed or Relapsed/Refractory Multiple Myeloma

NCT ID: NCT00903968

Last Updated: 2020-06-02

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

58 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-06-01

Study Completion Date

2016-10-31

Brief Summary

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The purpose of this research study is to determine the safety of plerixafor and bortezomib, and the highest dose that can be given to people safely. Plerixafor appears to stop myeloma cells from attaching to bone marrow and has been used in other phase I studies for mobilization of stem cells for patients with myeloma and lymphoma. We have shown that the combination of plerixafor and bortezomib is very effective in killing myeloma cells in the laboratory more than the effect of each drug alone.

Detailed Description

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Conditions

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Multiple Myeloma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase I Dose Level 1

Phase I Dose Level 1 patients received plerixafor 160ug/kg by injection on days 1-6 and bortezomib 1.0 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Plerixafor

Intervention Type DRUG

bortezomib

Intervention Type DRUG

Phase I Dose Level 2

Phase I Dose Level 2 patients received plerixafor 160ug/kg by injection on days 1-6 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Plerixafor

Intervention Type DRUG

bortezomib

Intervention Type DRUG

Phase I Dose Level 3

Phase I Dose Level 3 patients received plerixafor 240ug/kg by injection on days 1-6 and bortezomib 1.0 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Plerixafor

Intervention Type DRUG

bortezomib

Intervention Type DRUG

Phase I Dose Level 4

Phase I Dose Level 4 patients received plerixafor 240ug/kg by injection on days 1-6 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Plerixafor

Intervention Type DRUG

bortezomib

Intervention Type DRUG

Phase I Dose Level 5

Phase I Dose Level 5 patients received plerixafor 320ug/kg by injection on days 1-6 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Plerixafor

Intervention Type DRUG

bortezomib

Intervention Type DRUG

Phase I Dose Level 5B

Phase I Dose Level 5B patients received plerixafor 320ug/kg by injection on days 1, 2, 3, 6, 10, and 13 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Plerixafor

Intervention Type DRUG

bortezomib

Intervention Type DRUG

Phase I Dose Level 6

Phase I Dose Level 6 patients received plerixafor 400ug/kg by injection on days 1, 2, 3, 6, 10, and 13 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Plerixafor

Intervention Type DRUG

bortezomib

Intervention Type DRUG

All Phase I Participants

All Phase I participants received plerixafor by injection and bortezomib intravenously according to the established dose escalation schedule. Participants were treated until disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Plerixafor

Intervention Type DRUG

bortezomib

Intervention Type DRUG

All Phase II Participants

All Phase I participants received plerixafor 320ug/kg by injection on days 1, 2, 3, 6, 10, and 13, bortezomib 1.3 mg/m2 intravenously or subcutaneously days 3, 6, 10, and 13, and dexamethasone 40mg orally days 3, 6, 10, and 13 of each 21 day cycle during induction. In maintenance, participants received plerixafor, bortezomib, and dexamethasone days 1, 8, 15, and 22 of each 35 day cycle. Participants were treated until disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Plerixafor

Intervention Type DRUG

bortezomib

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

Interventions

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Plerixafor

Intervention Type DRUG

bortezomib

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

Other Intervention Names

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AMD3100 velcade Decadron

Eligibility Criteria

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Inclusion Criteria

* 18 years of age or older
* Must have received prior 1-5 therapies for their myeloma and have relapsed or refractory multiple myeloma. Prior therapy with bortezomib is allowed as long as they were not refractory to bortezomib
* Monoclonal protein serum of 1gm/dL or greater or monoclonal light chain in the urine protein electrophoresis of 200 mg/24 hours or greater, or measurable light chains by free light chain assay of 10 mg/dL or greater, or measurable plasmacytoma
* ECOG Performance Status 0, 1, or 2
* Laboratory values as outlined in the protocol

Exclusion Criteria

* Uncontrolled infection
* Cytotoxic chemotherapy \< 3 weeks, or biologic or targeted novel therapy \< 2 weeks, or corticosteroids \< 2 weeks prior to registration. Patients may be receiving chronic corticosteroids if they are being given for disorders other than myeloma
* Pregnant women
* Nursing women
* Men or women of child-bearing potential who are unwilling to employ adequate contraception
* Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational
* Known to be HIV positive
* Radiation therapy \< 2 weeks prior to registration
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Brigham and Women's Hospital

OTHER

Sponsor Role collaborator

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role collaborator

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role lead

Responsible Party

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Irene Ghobrial, MD

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Irene Ghobrial, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

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Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Cape Cod Hospital

Hyannis, Massachusetts, United States

Site Status

Milford Hospital

Milford, Massachusetts, United States

Site Status

Newton-Wellesley Hospital

Newton, Massachusetts, United States

Site Status

Cancer Treatment Centers of America (Eastern Regional Medical Center)

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

References

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Ghobrial IM, Liu CJ, Zavidij O, Azab AK, Baz R, Laubach JP, Mishima Y, Armand P, Munshi NC, Basile F, Constantine M, Vredenburgh J, Boruchov A, Crilley P, Henrick PM, Hornburg KTV, Leblebjian H, Chuma S, Reyes K, Noonan K, Warren D, Schlossman R, Paba-Prada C, Anderson KC, Weller E, Trippa L, Shain K, Richardson PG. Phase I/II trial of the CXCR4 inhibitor plerixafor in combination with bortezomib as a chemosensitization strategy in relapsed/refractory multiple myeloma. Am J Hematol. 2019 Nov;94(11):1244-1253. doi: 10.1002/ajh.25627. Epub 2019 Oct 4.

Reference Type DERIVED
PMID: 31456261 (View on PubMed)

Other Identifiers

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08-273

Identifier Type: -

Identifier Source: org_study_id

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