Trial of Three Stem Cell Mobilization Regimens for Multiple Myeloma

NCT01146834 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 1005011049X05324
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 5

Brief Summary

This phase III randomized trial compares three different peripheral stem cell mobilization regimens for patients with multiple myeloma who have received primary induction therapy or other therapies. Up to 180 patients will be enrolled. Patients eligible for treatment will be randomized to one of the three following mobilization regimens: Arm A = VELCADE, CYCLOPHOSPHAMIDE, \& G-CSF Arm B = VELCADE \& G-CSF Arm C = CYCLOPHOSPHAMIDE \& G-CSF Arm D = PLERIXAFOR \& G-CSF Arm E = PLERIXAFOR, VELCADE, \& G-CSF

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Number of Patients Able to Collect >=6 x 106 CD34+ Cells/kg in <= 2 Collections.

  The primary endpoint in all five treatment arms is the percentage of patients who are able to achieve greater than 6 x 106 CD34+ stems cells/kg harvested (defined as effectiveness). Note that no patients were enrolled Arm D and Arm E.

  36 months

Secondary Outcomes (2)

• Number of Patients Who Achieved Neutrophil Recovery After Melphalan 200 Based Transplant

  20 days post-transplant

• Number of Patients Who Achieved Platelet Recovery After Melphalan 200 Based Transplant

  20 days post-transplant

Study Arms (5)

Arm A: VELCADE, CYCLOPHOSPHAMIDE, & G-CSF

EXPERIMENTAL

VELCADE at 1.3 mg/m2 IVP on days 1, 4, 8 and 11 in combination with high-dose cyclophosphamide at 2.0 g/m2 on day 4. G-CSF is given for ten (+/- two) consecutive days starting on day 9 at a dose of 10 micrograms/kg/day. Pheresis will commence once ANC of 1.5 is reached.

Drug: bortezomib (Velcade); Drug: cyclophosphamide; Drug: G-CSF

Arm B: VELCADE & G-CSF

EXPERIMENTAL

VELCADE at 1.3 mg/m2 IVP on days 1, 4, 8 and 11. G-CSF is given for ten (+/- two) consecutive days starting on day 9 at a dose of 10 micrograms/kg/day. Day 12 start pheresis collection

Drug: bortezomib (Velcade); Drug: G-CSF

Arm C: CYCLOPHOSPHAMIDE & G-CSF

EXPERIMENTAL

High-dose cyclophosphamide at 2.0 g/m2 on day 1. G-CSF is given for ten (+/- two) consecutive days starting on day 2 at a dose of 10 micrograms/kg/day. Pheresis will commence once ANC of 1.5 is reached.

Drug: cyclophosphamide; Drug: G-CSF

Arm D: PLERIXAFOR & G-CSF

EXPERIMENTAL

G-CSF is given for ten (+/- two) consecutive days starting on day 1 at a dose of 10 micrograms/kg/day. Plerixafor is given on day 4, approximately 11 hours prior to stem cell collection attempt on Day 5. Both G-CSF and plerixafor are continued daily until collection is complete. Pheresis will commence for everyone on Day 5 regardless of ANC status.

Drug: G-CSF; Drug: Plerixafor

Arm E: PLERIXAFOR, VELCADE, & G-CSF

EXPERIMENTAL

Bortezomib at 1.3 mg/m2 IVP on days 1, 4, 8 and 11. G-CSF is given for ten (+/- wo) consecutive days starting on day 9 at a dose of 10 micrograms/kg/day. Plerixafor is given on day 12, approximately 11 hours prior to stem cell collection attempt and is continued daily until collection is complete. Pheresis will commence for everyone on Day 13 regardless of ANC status.

Drug: bortezomib (Velcade); Drug: G-CSF; Drug: Plerixafor

Interventions

bortezomib (Velcade) DRUG

1.3 mg/m2 IVP on days 1, 4, 8 and 11

Also known as: Velcade

Arm A: VELCADE, CYCLOPHOSPHAMIDE, & G-CSF; Arm B: VELCADE & G-CSF; Arm E: PLERIXAFOR, VELCADE, & G-CSF

cyclophosphamide DRUG

2.0 g/m2 (day 4 for Arm A and day 1 for Arm C)

Also known as: Cytoxan

Arm A: VELCADE, CYCLOPHOSPHAMIDE, & G-CSF; Arm C: CYCLOPHOSPHAMIDE & G-CSF

G-CSF DRUG

given for ten (+/- two) consecutive days starting on day 9 at a dose of 10 micrograms/kg/day (start on day 2 for Arm C and start on Day 1 for Arm D)

Also known as: Filgrastim, Neupogen

Arm A: VELCADE, CYCLOPHOSPHAMIDE, & G-CSF; Arm B: VELCADE & G-CSF; Arm C: CYCLOPHOSPHAMIDE & G-CSF; Arm D: PLERIXAFOR & G-CSF; Arm E: PLERIXAFOR, VELCADE, & G-CSF

Plerixafor DRUG

plerixafor is given on day 4, approximately 11 hours prior to stem cell collection attempt on Day 5, plerixafor daily until stem cell collection is complete (Arm D), start on Day 12, approximately 11 hours prior to stem cell collection attempt and plerixafor daily until collection if complete (Arm E)

Also known as: Mozobil

Arm D: PLERIXAFOR & G-CSF; Arm E: PLERIXAFOR, VELCADE, & G-CSF

Eligibility Criteria

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

You may qualify if:

• Voluntary written informed consent
• Confirmed diagnosis of multiple myeloma
• Age \> than 18 years at the time of signing the informed consent form.
• Karnofsky performance status above 60%
• Patients must be within 30 days of completing induction therapy.
• Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control .
• Male subject agrees to use an acceptable method for contraception for the duration of the study.
• Life expectancy \> 12 weeks.
• Subjects must have a MUGA scan or echo with LVEF \>50%
• Subjects must meet the following laboratory parameters:
• Absolute neutrophil count (ANC) ≥1500 cells/mm3
• Platelets count ≥ 50,000/mm3
• Hemoglobin \> 9.0 g/dL
• Serum SGOT/AST \<3.0 x upper limits of normal (ULN)
• Serum SGPT/ALT \<3.0 x upper limits of normal (ULN)

You may not qualify if:

• Patients with (no measurable monoclonal protein, free light chains, and/or M-spike in blood or urine) unless measurable disease is available with imaging techniques such as MRI and PET scan.
• History of allergic reactions to compounds containing boron, mannitol, VELCADE
• Prior history of other malignancies (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless disease free for \> = 5 years.
• NYHA Class III or IV heart disease. History of active unstable angina, congestive heart disease, severe uncontrolled cardiac arrhythmia, electrocardiographic evidence of acute ischemia, active conduction system abnormalities or myocardial infarction within 6 months prior to enrollment. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
• Female patients who are pregnant or breastfeeding. Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.
• Known HIV or hepatitis A, B, or C positivity---ONLY IF ACTIVE
• Active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program.
• Any concurrent, uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place him/her at unacceptable risk
• Patient has \> = Grade 2 peripheral neuropathy within 14 days before enrollment.
• Patient has received other investigational drugs with 14 days before enrollment
• Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (5)

Emory University

Atlanta, Georgia, 30322, United States

Location

New York University Cancer Institute

New York, New York, 10016, United States

Location

Columbia Presbyterian Medical Center):

New York, New York, 10032, United States

Location

Memorial Sloan-Kettering Cancer Center):

New York, New York, 10065, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Cyclophosphamide; Granulocyte Colony-Stimulating Factor; Filgrastim; plerixafor

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)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Limitations and Caveats

Arm B: VELCADE \& G-CSF was closed to further enrollment due to futility in 2013. Arm C: CYCLOPHOSPHAMIDE \& G-CSF was closed in 2015 due to futility. Early termination of Arm B and Arm C will limit the sample size for those treatment arms.

Results Point of Contact

• Title: Ruben Niesvizky, MD
• Organization: Weill Cornell Medicine

run9001@med.cornell.edu

646-962-9376

Study Officials

• Ruben Niesvizky, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2010
• First Posted: June 22, 2010
• Study Start: March 1, 2011
• Primary Completion: February 4, 2019
• Study Completion: February 4, 2019
• Last Updated: December 27, 2019
• Results First Posted: December 17, 2019

Record last verified: 2019-12

Locations

US (5)