Basiliximab #2: In-Vivo Activated T-Cell Depletion to Prevent Graft-Versus_Host Disease (GVHD) After Nonmyeloablative Allotransplantation for the Treatment of Blood Cancer

Multiple Myeloma Clinical Trial

Official title:

Basiliximab #2: In-Vivo Activated T-Cell Depletion to Prevent GVHD After Nonmyeloablative Allotransplantation for the Treatment of Blood Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00975975
• Other study ID #: 0908-04; IUCRO-0256
• Status: Completed
• Phase: Phase 2
• First received: September 11, 2009
• Last updated: January 28, 2016
• Start date: September 2009
• Est. completion date: November 2013

Study information

• Verified date: January 2016
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the effects (good and bad) of the medication basiliximab in combination with cyclosporine (investigational therapy) for the prevention of a complication of bone marrow transplantation known as graft-versus-host disease (GVHD). GVHD is a complication in which the cells of the transplanted bone marrow react against organs and tissues.

Description:

This study is for patients with a blood condition or myelodysplasia (bone marrow disease) which has either not responded to treatment or is not treatable by conventional/routine medical treatments. Bone marrow transplantation is a medical treatment that involves giving high doses of chemotherapy followed by the transplantation of the blood-forming and immune cells from a relative or from a "matched" unrelated person through the National Marrow Donor Program, in an attempt to cure disease in the recipient (the person receiving the donated cells). Nonmyeloablative (bone-marrow preservation) bone marrow transplantation is a relatively new technique in which lower than usual doses of chemotherapy are given before transplantation, in hopes of reducing adverse side effects of the chemotherapy in transplant patients. Nonmyeloablative bone marrow transplantation has several advantages which doctors have determined are beneficial for this condition.

This research is being done because the complication of graft-versus-host disease can be bad for a person and there is no completely safe and effective way to prevent this complication. We know that cyclosporine helps but would like to know if the addition of basiliximab, given with cyclosporine, will decrease the incidence and/or severity of graft-versus-host disease after a transplant known as nonmyeloablative or "mini" transplant.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: November 2013
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Acute myelogenous leukemia:

• Second or subsequent remission; patient over 18 yrs of age.

• Relapsed after autologous HC transplant, over 18 years of age.

• First remission, Philadelphia chromosome + over age 18.

• Secondary AML, in first or subsequent remissions.

• Acute lymphocytic leukemia:

• Philadelphia chromosome + over the age of 50, first or subsequent remission.

• Relapse following Autologous HC transplantation, ages over 50.

• Second or subsequent remission over the age of 50

• Chronic myelogenous leukemia:

• First or second chronic phase over the age of 18.

• Accelerated phase over the age of 18.

• Must have failed or been intolerant to a standard tyrosine kinase inhibitor.

• Chronic lymphocytic leukemia:

• Failed nucleoside-based therapy, ages >18.

• Myelodysplasia:

• All-risk categories, age greater than 18.

• Non-Hodgkin's Lymphoma, less than 76 years of age

• Relapsed diffuse aggressive NHL (intermediate and high grade) that fails to achieve CR or PR to conventional salvage chemotherapy.

• Aggressive NHL includes diffuse large B cell lymphoma, diffuse mixed small and large cell lymphoma, follicular lymphoma for grade 3 (follicular large cell lymphoma), T or B cell lymphoblastic lymphoma, diffuse small noncleaved (Burkett's or Burkett-like ) lymphoma, mantle cell lymphoma, peripheral T cell lymphoma, anaplastic large cell lymphoma, and other diffuse aggressive lymphomas that are not otherwise classifiable

• Aggressive NHL that has relapsed following autologous HCT. Patients that respond to additional treatment for post-transplant relapse are eligible.

• Aggressive NHL that does not achieve CR or PR with primary chemotherapy (i.e., primary induction failure).

• Low-grade lymphoma refractory to standard therapy, including the following:

1. small cell lymphocytic lymphoma,

2. follicular lymphoma of grades 1 and 2 (follicular small cleaved and follicular mixed small and large cell lymphoma)

3. marginal cell lymphoma, splenic lymphoma),

4. lymphoplasmacytic lymphoma and

5. other lymphomas not otherwise classifiable.

• Patients with low-grade lymphoma must have experienced progressive disease after receiving three or more of the following regimens:

• alkylator-based therapy (cyclophosphamide/ vincristine/ prednisone) chlorambucil, monoclonal antibody based therapy (e.g., rituximab, Campath-1H, radiolabelled CD20+ antibodies);

• nucleoside analog-based therapy (e.g., fludarabine, cladribine).)

• Patients with marginal zone lymphoma or gastric MALT type associated with Helicobacter pylori infection must have progressed after receiving appropriate antibiotic therapy as well as three or more regimens as described above

• Mantle cell, ages 18-75.

• Hodgkin's Disease, ages 18-75.

• Relapsed or refractory disease after autologous transplant.

• Multiple Myeloma, ages 18-75

• Recurrent disease after two medical therapies

• Relapse following autologous transplant

• Myelofibrosis, age greater than 18 years

• Severe aplastic anemia (refractory to immunosuppressive therapy); age greater than 18 years

• Patients with aplastic anemia must have marrow cellularity = 10% plus 2 of the following:

1. Absolute granulocyte count <500/mm3

2. Corrected reticulocyte count <1%

3. Untransfused platelet count <20,000/mm3 on at least 2 occasions

4. Hemoglobin <9 g/dL (adults) or < 8 g/dL (children) on at least 2 occasions

• Paroxysmal nocturnal hemoglobinuria; age greater than 18 years.

• Renal function: creatinine greater than 2.5

• Donor Requirement:

• Must have a fully HLA-matched (10 of 10 Antigen matched) related or unrelated donor, eighteen years of age or older, who is capable of undergoing GCSF mobilization and apheresis

Exclusion Criteria:

• Active CNS disease (the presence of leukemic blasts in the CSF)

• Pregnancy or breast-feeding.

• Inability to give informed consent.

• AST, ALT, total bilirubin >3x upper limit of normal.

• Creatinine > 2 or creatinine clearance < 50mL/hr. If patient has a creatinine of > 2 or creatinine clearance < 50mL/hr and it is due to the disease process then the patient will not be excluded based on this.

• Fractional shortening by echocardiogram not within normal limits per institution or LVEF of < 40 %.

• Pulmonary function: DLCO not within institutional normal limits or DLCO less than 45% of normal predicted, corrected for anemia

• Prior allogeneic transplant.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Lymphocytic Leukemia
• Acute Myelogenous Leukemia
• Anemia, Aplastic
• Chronic Lymphocytic Leukemia
• Chronic Myelogenous Leukemia
• Hemoglobinuria
• Hemoglobinuria, Paroxysmal
• Hodgkin Disease
• Hodgkin's Disease
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Myelodysplasia
• Myelodysplastic Syndromes
• Myelofibrosis
• Non-Hodgkin's Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia

Intervention

Drug:
• Basiliximab
Basiliximab given 1 time on Day +7 or Day +9.

Locations

Country	Name	City	State
United States	Indiana University Cancer Center	Indianapolis	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Indiana University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Grade 3-4 Acute GVHD Rate	The percent of patients where a patient experienced a Grade 3 or 4 acute GVHD	Transplant (Day 0) up to 1 year	Yes
Secondary	Time to Neutrophil Engraftment	Time to neutrophil engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of neutrophils is defined as the time from day 0 to the date of the first of three consecutive days after transplantation during which the absolute neutrophils count (ANC) is at least 0.5 x109/l. Patients who did not have neutrophil engraftment before death will be censored at the date of death. The median and 95% confidence intervals will be provided.	Transplant (Day 0) up to 1 year	No
Secondary	Time to Platelet Engraftment	Time to platelet engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of platelets is defined as the time from day 0 to the first of seven consecutive days after transplantation during which the platelet count is at least 20 x109/l without transfusion support. Patients who did not have platelet engraftment before death will be censored at the date of death. The median and 95% confidence intervals will be provided.	Transplant (Day 0) up to 1 year	No