Plerixafor and Sargramostim (GM-CSF) for Mobilization of Allogeneic Sibling Donors

NCT01158118 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 10-1154 / 201108083
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This study will gather information about the combination the drugs plerixafor with sargramostim in donors of blood-forming cells (stem cells). These stem cells will be collected from the donor and transplanted into their sibling. The investigators believe that the two drugs together will provide enough stem cells for transplantation and may also reduce the risk of graft versus host disease.

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Lymphoma, Non-Hodgkin; Hodgkin Disease; Leukemia, Lymphocytic, Chronic, B-Cell; Multiple Myeloma

Keywords

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Outcome Measures

Primary Outcomes (1)

• Number of Donors Requiring a Second Collection to Obtain a Minimum CD34/Kg (2 x 10^6) Necessary for Allogeneic Stem Cell Transplantation

  The primary endpoint is to reduce the number of donors treated with GM-CSF who require a second collection to obtain a minimum CD34/Kg (2 x 106) necessary for allogeneic stem cell transplantation when compared to historic controls mobilized with GM-CSF or plerixafor alone. A reduction in failed first leukapheresis from 40% to less than 10% as seen with G-CSF alone would be considered clinically meaningful.

  Up to 6 days

Secondary Outcomes (11)

• Proportion of Donors Who Experience Grade 3-4 Infusion Toxicity

  30 days after completion of therapy (estimated to be 36 days)

• Number of Donors Who Mobilize ≥ 2x10^6 CD34+ Cells/Kg Recipient Weight Safely Following One or Two Aphereses

  Up to 6 days

• Percentage of Donors Who Reach 5x10^6 CD34+ Cells/Kg Recipient Weight in 1 or 2 Aphereses

  6 days

• Determine if Peripheral Blood Stem Cell Products Collected After Mobilization With IV Plerixafor Can be Used Safely for Hematopoietic Cell Transplantation in HLA-matched Recipients as Measured by Time to Neutrophil Engraftment (Recipient Only)

  Up to Day 21

• Kinetics of Immune Reconstitution as Measured by Time to Neutrophil Engraftment (Recipient Only)

  Up to Day 100

Study Arms (2)

Arm 1 - Donor

EXPERIMENTAL

Days 1-5: Mobilization with 5 mcg/kg/day GM-CSF (first 4 donors were mobilized with 10 mcg/kg GM-CSF then changed to 5 mcg/kg for remaining donors) Day 5: Mobilization with 320 mcg/kg plerixafor IV Day 5: Leukopheresis If PBSC collected are not adequate, then donor will be mobilized with GM-CSF and plerixafor IV on day 6 and have leukopheresis collection on day 6.

Drug: Sargramostim; Drug: Plerixafor

Arm 2 - Recipient

NO INTERVENTION

Conditioning Regimens * fludarabine and busulfan +/- thymoglobulin * fractionated total body irradiation and cyclophosphamide * busulfan and cyclophosphamide * single dose total body irradiation and cyclophosphamide Day -2 = GvHD prophylaxis Day 0 or +1 = PBSC transplant Day +7 until neutrophil engraftment = G-CSF 5 ug/kg/day

Interventions

Sargramostim DRUG

Also known as: GM-CSF, Leukine

Arm 1 - Donor

Plerixafor DRUG

Also known as: AMD3100, Mozobil

Arm 1 - Donor

Eligibility Criteria

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

You may qualify if:

• Donor Eligibility
• Donor is 18 to 65 years of age inclusive.
• If female and of child-bearing age, donor must be non-pregnant, not breastfeeding, and agree to use adequate contraception.
• Donor is a 6/6 HLA-matched sibling willing to donate PBSC for transplant.
• Donor has adequate cardiac function with no history of congestive heart failure and no history of atrial fibrillation or ventricular tachyarrhythmia.
• Donor has adequate renal function as defined by a calculated serum creatinine clearance of ≥56 ml/min for females and ≥64 ml/min for males.
• Donor has adequate hepatic function as defined by a total bilirubin \<2x normal or absence of hepatic fibrosis/cirrhosis.
• Donor has adequate neurologic function as defined by NO evidence of a severe central or peripheral neurologic abnormality. No history of cerebrovascular accident or seizure disorder requiring anticonvulsant medication.
• Donor must be HIV-1\&2 antibody and HTLV-I\&II antibody sero-negative, by FDA licensed test.
• Donor must have an ECOG performance status of 0 or 1.
• Donor must demonstrate ability to be compliant with study regimen.
• Donor must not have an active infection at the time of study entry.
• Donor does not have active alcohol or substance abuse within 6 months of study entry.
• Donor is not currently enrolled on another investigational agent study.
• Donor does not have any medical condition, which, in the opinion of the clinical investigator, would interfere with his/her evaluation.

You may not qualify if:

• Donor may not be receiving any other investigational agents.
• Donor may not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to plerixafor or GM-CSF, or known hypersensitivity to yeast-derived products or any component of the product.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Lymphoma, Non-Hodgkin; Hodgkin Disease; Leukemia, Lymphocytic, Chronic, B-Cell; Multiple Myeloma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor; plerixafor

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Myeloproliferative Disorders

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Mark Schroeder, M.D.
• Organization: Washington University School of Medicine

markschroeder@wustl.edu

314-454-8304

Study Officials

• Mark Schroeder, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2010
• First Posted: July 8, 2010
• Study Start: April 1, 2011
• Primary Completion: January 15, 2014
• Study Completion: December 31, 2016
• Last Updated: June 5, 2017
• Results First Posted: May 3, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)