Clinical trial NCT00903968: Combination Plerixafor (AMD3100)and Bortezomib in Relapsed or Relapsed/Refractory Multiple Myeloma
Official title: Phase I/II Trial of Combination Plerixafor (AMD3100) and Bortezomib in Relapsed or Relapsed/Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: refractory
relapsed
bortezomib
AMD3100
plerixafor
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
name: Genzyme, a Sanofi Company
name: Millennium Pharmaceuticals, Inc.
First posted: 2009-05-19
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Plerixafor Maximum Tolerated Dose (MTD) [Phase I]
timeFrame: Participants were assessed every 3 weeks while on study; The observation period for MTD evaluation was the first 21 days of treatment.
measure: Bortezomib Maximum Tolerated Dose (MTD) [Phase I]
timeFrame: Participants were assessed every 3 weeks while on study; The observation period for MTD evaluation was the first 21 days of treatment.
measure: Number of Participants With Dose Limiting Toxicity (DLT) [Phase I]
timeFrame: Participants were assessed every 3 weeks while on study; The observation period for MTD evaluation was the first 21 days of treatment.
measure: Response Rate of Plerixafor, Bortezomib, and Dexamethasone in Relapsed or Relapsed/ Refractory Multiple Myeloma (ORR) [Phase I and Phase II]
timeFrame: Disease was assessed for response every cycle on treatment. The maximum number of cycles received was 25.
Secondary outcomes:
measure: Time to Progression (TTP) [Phase II]
timeFrame: DIsease was assessed to document progression every cycle on treatment and post-treatment every 12 weeks until progression.
measure: Duration of Response (DOR) [Phase II]
timeFrame: DIsease was assessed to document response every cycle on treatment and post-treatment every 12 weeks until progression.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Hyannis
country: United States
facility: Cape Cod Hospital
state: Massachusetts
city: Milford
country: United States
facility: Milford Hospital
state: Massachusetts
city: Newton
country: United States
facility: Newton-Wellesley Hospital
state: Massachusetts
city: Philadelphia
country: United States
facility: Cancer Treatment Centers of America (Eastern Regional Medical Center)
state: Pennsylvania
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Irene Ghobrial, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.