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

NCT00903968 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 08-273
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Multiple Myeloma

Keywords

refractory; relapsed; bortezomib; AMD3100; plerixafor

Outcome Measures

Primary Outcomes (4)

• Plerixafor Maximum Tolerated Dose (MTD) [Phase I]

  The MTD plerixafor in combination with bortezomib is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as highest dose level at which fewer than one-third of patients experience a DLT. The MTD was reached at dose level 5B. The maximum tolerated dose of plerixafor was given on days 1, 2, 3, 6, 10, 13 of 21 each cycle.

  Participants were assessed every 3 weeks while on study; The observation period for MTD evaluation was the first 21 days of treatment.

• Bortezomib Maximum Tolerated Dose (MTD) [Phase I]

  The MTD plerixafor in combination with bortezomib is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as highest dose level at which fewer than one-third of patients experience a DLT. The MTD was reached at dose level 5B. The maximum tolerated dose of bortezomib was given on days 3, 6, 10, 13 of 21 each cycle.

  Participants were assessed every 3 weeks while on study; The observation period for MTD evaluation was the first 21 days of treatment.

• Number of Participants With Dose Limiting Toxicity (DLT) [Phase I]

  A DLT was defined as (a) grade 3 or greater non-hematologic toxicity, considered by the investigator to be related to plerixafor or bortezomib, with the exception of nausea, vomiting or diarrhea unless receiving maximal medical therapy, (b) grade 4 hematologic toxicity defined as: thrombocytopenia with platelets \<10,000 on more than one occasion within first cycle despite transfusion. Grade 4 neutropenia must occur for more than 5 days and/or result in neutropenic fever with elevated temperature (defined as \> 101 degrees F). (c) inability to receive Day 1 dose for Cycle 2 due to toxicity. All adverse events were graded according to the CTEP Common Toxicity Criteria (CTCAE v.3.0).

  Participants were assessed every 3 weeks while on study; The observation period for MTD evaluation was the first 21 days of treatment.

• Response Rate of Plerixafor, Bortezomib, and Dexamethasone in Relapsed or Relapsed/ Refractory Multiple Myeloma (ORR) [Phase I and Phase II]

  Overall response was established based on International Myeloma Working Group (IMWG) criteria with 6 potential categories: Complete Response (CR) which is a complete disappearance of monoclonal paraprotein based on negative immunofixation on the serum M-component and urine M-component and no evidence of myeloma in bone marrow, Very Good Partial Response (VGPR) defined as serum and urine M-component detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-component plus urine M-component \<100 mg per 24 hours, Partial Response (PR) ≥50% reduction in serum M-component or ≥90% reduction urine M-component or urine M-component \<200 mg per 24 hours, Minimal Response (MR) ≥25% reduction in serum or urine M-component, Stable Disease (SD) defined as failure to meet any response criteria, and Progressive Disease (PD) ≥ 25% increase from lowest value reported in serum M-component (absolute ≥0.5 g/dL) and/or urine M-component (absolute ≥200 mg/24 hours).

  Disease was assessed for response every cycle on treatment. The maximum number of cycles received was 25.

Secondary Outcomes (2)

• Time to Progression (TTP) [Phase II]

  DIsease was assessed to document progression every cycle on treatment and post-treatment every 12 weeks until progression.

• Duration of Response (DOR) [Phase II]

  DIsease was assessed to document response every cycle on treatment and post-treatment every 12 weeks until progression.

Study Arms (9)

Phase I Dose Level 1

EXPERIMENTAL

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.

Drug: Plerixafor; Drug: bortezomib

Phase I Dose Level 2

EXPERIMENTAL

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.

Drug: Plerixafor; Drug: bortezomib

Phase I Dose Level 3

EXPERIMENTAL

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.

Drug: Plerixafor; Drug: bortezomib

Phase I Dose Level 4

EXPERIMENTAL

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.

Drug: Plerixafor; Drug: bortezomib

Phase I Dose Level 5

EXPERIMENTAL

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.

Drug: Plerixafor; Drug: bortezomib

Phase I Dose Level 5B

EXPERIMENTAL

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.

Drug: Plerixafor; Drug: bortezomib

Phase I Dose Level 6

EXPERIMENTAL

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.

Drug: Plerixafor; Drug: bortezomib

All Phase I Participants

EXPERIMENTAL

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.

Drug: Plerixafor; Drug: bortezomib

All Phase II Participants

EXPERIMENTAL

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.

Drug: Plerixafor; Drug: bortezomib; Drug: Dexamethasone

Interventions

Plerixafor DRUG

Also known as: AMD3100

All Phase I Participants; All Phase II Participants; Phase I Dose Level 1; Phase I Dose Level 2; Phase I Dose Level 3; Phase I Dose Level 4; Phase I Dose Level 5; Phase I Dose Level 5B; Phase I Dose Level 6

bortezomib DRUG

Also known as: velcade

All Phase I Participants; All Phase II Participants; Phase I Dose Level 1; Phase I Dose Level 2; Phase I Dose Level 3; Phase I Dose Level 4; Phase I Dose Level 5; Phase I Dose Level 5B; Phase I Dose Level 6

Dexamethasone DRUG

Also known as: Decadron

All Phase II Participants

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Brigham and Women's Hospital: collaborator
• Genzyme, a Sanofi Company: collaborator
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (5)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Cape Cod Hospital

Hyannis, Massachusetts, 02601, United States

Location

Milford Hospital

Milford, Massachusetts, 01757, United States

Location

Newton-Wellesley Hospital

Newton, Massachusetts, 02462, United States

Location

Cancer Treatment Centers of America (Eastern Regional Medical Center)

Philadelphia, Pennsylvania, 19124, United States

Location

Related Publications (1)

• 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.

  PMID: 31456261 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

plerixafor; Bortezomib; Dexamethasone; Calcium Dobesilate

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Irene M. Ghobrial, MD
• Organization: Dana-Farber Cancer Institute

Irene_Ghobrial@dfci.harvard.edu

617-632-4198

Study Officials

• Irene Ghobrial, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 18, 2009
• First Posted: May 19, 2009
• Study Start: June 1, 2009
• Primary Completion: June 1, 2016
• Study Completion: October 1, 2016
• Last Updated: June 2, 2020
• Results First Posted: September 29, 2017

Record last verified: 2020-05

Locations

US (5)