Dose Escalation Trial of Denileukin Diftitox (Ontak) Post Autologous Transplantation

NCT01251952 | Terminated Phase 1 Results DMC

• 1 other identifier: WSU 2010-039
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

The primary goal of this study is to determine the feasibility and safety of giving two doses of denileukin diftitox (DD) at days 0 and 21 post autologous stem cell transplantation in a dose escalation fashion. Secondary goals include evaluating the the effect of DD on the number and percentage of T-regs in the peripheral blood post transplant at each dose level, the effect of DD on T cell (CD4/CD8) reconstitution post transplant at each dose level and determining the time to engraftment: absolute neutrophil count (\>0.5 x 10\^9/L for 3 consecutive days), and platelet (\>20X 10\^9/L for 3 consecutive days). The hypothesis for the study is based on the ability of DD to deplete T-regs and subsequently enhance the immune reconstitution and reverse post transplant lymphopenia. This may indirectly enhance the efficacy of autologous transplantation and reduce disease relapse.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Assess Toxicities of Giving Two Doses of Ontak at Days 0 and 21 Post Autologous Stem Cell Transplantation in a Dose Escalation Fashion.

  After drug infusion, participants will be closely monitored for at least 4 hours for side effects

  Up to 21 days post transplant

Secondary Outcomes (3)

• To Evaluate the Effect of Ontak on the Number and Percentage of Regulatory T Cells in the Peripheral Blood Post Transplant at Each Dose Level.

  days 0 and 21 post autologous stem cell transplantation

• To Evaluate the Effect of Ontak on T Cell CD4/CD8 Reconstitution Post Transplant at Each Dose.

  days 0 and 21 post autologous stem cell transplantation

• To Evaluate the Effect of Ontak on Engraftment of Neutrophils and Platelets Post Transplant at Each Dose.

  days 0 and 21 post autologous stem cell transplantation

Study Arms (1)

Denileukin Diftitox (Ontak)

EXPERIMENTAL

Denileukin Diftitox (Ontak) administered Post Autologous Transplantation.

Drug: Denileukin Diftitox (Ontak)

Interventions

Denileukin Diftitox (Ontak) DRUG

After receiving their stem cell transplant on Day 0, participants will receive study agent via a 30 minute infusion. Participants will also receive a 30 minute infusion of study agent on Day 21. Follow-up visits for clinical assessment, blood draws for routine clinical laboratory studies and for immuno-correlative studies will also take place on days 42, 90, 180 and 360.

Also known as: Ontak®

Denileukin Diftitox (Ontak)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients age \> =18 who have been diagnosed with Multiple Myeloma and are scheduled for autologous peripheral blood hematopoietic stem cell transplant (AHSCT) will be screened for eligibility.
• Diagnosis of Multiple Myeloma
• Age \>=18 and no more than 70 years.
• Able to understand and sign a consent form.
• Can collect peripheral blood stem cells with a CD34+ cell dose of at least 5.0 x 106/kg. The CD34 molecule is a Cluster of Differentiation molecule present on hematopoietic stem cells.
• Conditioning regimen to be high dose Melphalan at a dose of 200mg/m2.
• Karnofsky Performance Score (KPS) \>60 or ECOG (Eastern Cooperative Oncology Group) performance status \<=2
• Kidney function:Creatinine \<2.0 mg/dl or creatinine clearance \>50 ml/min
• Heart function: Ejection fraction \>45%
• Liver function tests :Serum bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) less than 3 X upper limit of normal
• Lung function tests: Forced Vital Capacity (FVC), Forced Expiratory Volume in One Second (FEV1) or Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) \>45% predicted

You may not qualify if:

• Age \<18 years or \> 70 years
• Previous exposure to denileukin diftitox.
• Patients with documented uncontrolled central nervous system (CNS) disease.
• Previous AHSCT.
• Significant organ dysfunction deemed to be inappropriate for autologous transplantation.

Sponsors & Collaborators

• Barbara Ann Karmanos Cancer Institute: lead
• Eisai Inc.: collaborator

Study Sites (1)

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

denileukin diftitox

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

Limitations and Caveats

Analysis was not completed due to the small number of patients accrued and drugs were unavailable.

Results Point of Contact

• Title: Zaid Al-Kadhimi, M.D.
• Organization: Barbara Ann Karmanos Cancer Institute

alkadhiz@karmanos.org

(313) 576-8022

Study Officials

• Zaid Al-Kadhimi, M.D.

  Barbara Ann Karmanos Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: November 30, 2010
• First Posted: December 2, 2010
• Study Start: November 1, 2010
• Primary Completion: July 1, 2011
• Study Completion: May 1, 2013
• Last Updated: June 20, 2017
• Results First Posted: December 16, 2013

Record last verified: 2017-05

Locations

US (1)