Tacrolimus and Thymoglobulin, as GvHD Prophylaxis in Patients Undergoing Related Donor HCT

NCT01246206 | Completed Phase 2 Results DMC

• 1 other identifier: WSU 2009-095
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

The primary goal of the study is to determine the incidence and severity of acute Graft versus Host Disease (GVHD) following human leukocyte antigen (HLA) matched related donor Hematopoetic Stem Cell(HSC) transplant in patients with blood related cancers who receive the combination of tacrolimus and Thymoglobulin as GVHD prophylaxis. The investigators also will determine the safety of this combination in the first six months post transplant. Secondary goals include determining the time to recovery of white blood cells and platelets (engraftment), determining the occurrence of opportunistic infections, defined as infection that occurs in people with weakened immune systems and caused by organisms that do not normally cause disease (fungal infections, pneumocystis carinii pneumonia (PCP), and viral infections), estimating the incidence of chronic GVHD at two years and the overall and disease free survival at two years. Immune response will be assessed by means of immuno-correlative studies both prior to and at various points after transplant.

Conditions

Hematological Malignancies

Keywords

● Non-Hodgkin lymphoma,; ● Hodgkin disease,; ● Acute Myelogenous or Acute Lymphocytic Leukemia; ● Myelodysplastic Syndromes,; ● Chronic Myelogenous Leukemia; ● Multiple Myeloma; ● Chronic Lymphocytic Leukemia; ● Myelofibrosis and other myeloproliferative disorders;

Outcome Measures

Primary Outcomes (3)

• Incidence of Acute GVHD

  Cumulative Incidence of grade II-V acute GVHD with relapse or NRM as competing risks

  Assessed first 6 months post transplant

• Safety Defined by Serious Adverse Events

  Counted the number of participants that experienced any type of grade 3 or higher toxicity.

  Assessed first 6 months post transplant

• Severity of Acute GVHD

  Cumulative Incidence of grade III-V acute GVHD with relapse or NRM as competing risks

  Assessed first 6 months post transplant

Secondary Outcomes (5)

• Determine Incidence of Opportunistic Infections

  Followed for up to two years post transplant

• Estimate Incidence of Chronic GVHD at Two Years

  Followed for up to two years post transplant

• Overall Survival at Two Year,

  Followed for up to two years post transplant

• Determine Time to Engraftment ("G500")

  Followed for up to two years post transplant

• Determine Time to Engraftment ("PLT20")

  Followed for up to two years post transplant

Study Arms (1)

Tacrolimus and Thymoglobulin

EXPERIMENTAL

Tacrolimus and Thymoglobulin, as Graft-versus-Host-Disease Prophylaxis

Drug: Tacrolimus and Thymoglobulin

Interventions

Tacrolimus and Thymoglobulin DRUG

Intravenous Tacrolimus 0.03 mg/kg/d, beginning day -3, where day 0 is the day of stem cell infusion or "transplant." Intravenous tacrolimus will be discontinued once the participant starts eating, and the drug will then be given orally at a dose of approximately 4 times the intravenous dose. Tacrolimus will be discontinued starting 100 days after transplant unless signs of acute and chronic GVHD develop or if severe toxicity occurs. Thymoglobulin will be given 0.5 mg/kg day-3, Thymoglobulin 1.5 mg/kg day -2, Thymoglobulin 2.5 mg/kg day -1. Thymoglobulin will be given intravenously over 6 hours.

Also known as: PROGRAF®

Tacrolimus and Thymoglobulin

Eligibility Criteria

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

You may qualify if:

• Suitable related donor as determined by the treating physician
• High resolution molecular HLA typing is mandatory for HLA Class I and II
• Diagnosis of hematological malignancy
• Patients with one of the following hematologic malignancies, and felt to be transplant candidates by their treating physician are eligible to enroll on this protocol:
• Non-Hodgkin lymphoma, any complete remission (CR)/partial remission (PR)
• Hodgkin disease, any CR/PR/stable disease (SD)
• Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) any CR; for non-CR AML or ALL, bone marrow blast \< 20% within 4 weeks of transplant and peripheral blood (PB) absolute blast count \< 500/μl on the day of initiation of conditioning
• Myelodysplastic syndrome (MDS), treated or untreated
• Chronic myelogenous leukemia (CML) in chronic phase or accelerated phase
• Chronic myelomonocytic leukemia (CMML)
• Multiple myeloma, any CR/PR/SD
• Chronic lymphocytic leukemia (CLL) any CR/PR
• Myelofibrosis and other myeloproliferative disorders; bone marrow blasts less than 20 percent within four weeks of transplant and peripheral blood absolute blast counts less than 500 per microliter on the day of initiation of conditioning
• Age \>= 18 and able to cooperate with oral medication intake
• Filgrastim (G-CSF) mobilized Peripheral blood stem cells

You may not qualify if:

• Bone marrow or Ex vivo engineered or processed graft (cluster of differentiation \[CD\]34+ enrichment, T-cell depletion, etc)
• Patients with documented uncontrolled central nervous system (CNS) disease
• Active donor or recipient serology positive for human immunodeficiency virus (HIV)
• Known contraindication to administration of Tacrolimus or Thymoglobulin
• Active Hepatitis B or C
• Patients with coronary heart disease (recent myocardial infarctions, angina, cardiac stent, or bypass surgery in the last 6 months) need to be cleared with a stress echocardiogram or nuclear myocardial perfusion stress test, and cardiology consult; all other cardiac history will be at the discretion of the Principal Investigator
• Oxygen usage at the time of enrollment
• Patients with clinical ascites
• Women who are pregnant or nursing

Sponsors & Collaborators

• Barbara Ann Karmanos Cancer Institute: lead

Study Sites (1)

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms; Lymphoma, Non-Hodgkin; Hodgkin Disease; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Multiple Myeloma; Leukemia, Lymphocytic, Chronic, B-Cell; Primary Myelofibrosis

Interventions

Tacrolimus; thymoglobulin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Bone Marrow Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; 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; Leukemia, B-Cell

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

The small number of patients makes the data hard to interpret.

Results Point of Contact

• Title: Dr. Zaid Al-Kadhimi
• Organization: Barbara Ann Karmanos Cancer Institute

zalkadh@emory.edu

800-527-6266

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 2
• Allocation: NA
• 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 21, 2010
• First Posted: November 23, 2010
• Study Start: November 1, 2010
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: June 18, 2018
• Results First Posted: June 1, 2017

Record last verified: 2018-05

Locations

US (1)