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

Dana-Farber Cancer Institute

Status and phase: Completed; Phase 2; Phase 1

Conditions: Multiple Myeloma

Treatments: Drug: bortezomib; Drug: Plerixafor; Drug: Dexamethasone

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00903968

08-273

Details and patient eligibility

About

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.

Enrollment: 58 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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58 participants in 9 patient groups

Phase I Dose Level 1

Experimental group

Description:

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.

Treatment:

Drug: Plerixafor

Drug: bortezomib

Phase I Dose Level 2

Experimental group

Description:

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.

Treatment:

Drug: Plerixafor

Drug: bortezomib

Phase I Dose Level 3

Experimental group

Description:

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.

Treatment:

Drug: Plerixafor

Drug: bortezomib

Phase I Dose Level 4

Experimental group

Description:

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.

Treatment:

Drug: Plerixafor

Drug: bortezomib

Phase I Dose Level 5

Experimental group

Description:

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.

Treatment:

Drug: Plerixafor

Drug: bortezomib

Phase I Dose Level 5B

Experimental group

Description:

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.

Treatment:

Drug: Plerixafor

Drug: bortezomib

Phase I Dose Level 6

Experimental group

Description:

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.

Treatment:

Drug: Plerixafor

Drug: bortezomib

All Phase I Participants

Experimental group

Description:

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.

Treatment:

Drug: Plerixafor

Drug: bortezomib

All Phase II Participants

Experimental group

Description:

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.

Treatment:

Drug: Dexamethasone

Drug: Plerixafor

Drug: bortezomib