Stem Cell Transplant for Hematologic Diseases

Phase 1

Terminated

Conditions: Hematologic Malignancies

Interventions: Biological: Campath 1H
Drug: Fludarabine
Procedure: Stem Cell Transplant
Radiation: Total Body Irradiation (TBI)
Drug: FK506 (Tacrolimus) or Cyclosporine

Registration Number: NCT00058825

Lead Sponsor: Baylor College of Medicine

Brief Summary: Patients are being asked to participate in this study because they have a cancer in their blood, Fanconi's Anemia, or have been unsuccessfully treated for bone marrow failure such as Aplastic Anemia or Paroxysmal Nocturnal Hemoglobinuria. Any of these conditions could benefit from an allogeneic stem cell transplant using a donor that is related to the patient.

Stem cells are created in the bone marrow. They grow into different types of blood cells that the patient needs, including red blood cells, white blood cells, and platelets. In a transplant, the patient's own stem cells are killed and then replaced by stem cells from the donor.

Usually, patients are given very strong doses of chemotherapy prior to receiving a stem cell transplant. However, because of the patient's condition, they have a high risk of experiencing life-threatening treatment-related side-effects. Recently, some doctors have begun to use chemotherapy that does not cause as many side-effects before patients receive a transplant.

This research study adds CAMPATH 1H to a low-dose chemotherapy regimen, followed by an allogeneic stem cell transplantation. We want to see whether adding CAMPATH 1H to the transplant medications helps in treating the disease. We also want to see whether there are fewer life-threatening side-effects from the treatment. CAMPATH 1H is a drug that is still being studied. CAMPATH 1H stays active in the body for a long time after patients receive it, which means it may work longer at preventing graft-versus-host-disease (GvHD) symptoms.

Detailed Description: Before treatment begins, stem cells will be collected from the donor's blood or bone marrow. The stem cells will be collected and frozen before we start to give the patient chemotherapy.

After admission to the hospital, patients will receive total body irradiation (very strong x-rays that kill cells in the bone marrow), Fludarabine and Campath 1H prior to the stem cell transplant (infusion of the donor's stem cells).

Starting 7 days after the transplant, the patient will be given G-CSF by subcutaneous injection, until a blood test shows that numbers of granulocytes (a type of white blood cell) in the blood are more than 1,000/uL. This is to help increase blood cell counts.

After transplantation, the patient will undergo several evaluations at different times. These are standard evaluations and tests performed for any patient who has received a stem cell transplant, as part of routine clinical monitoring.

We will also be looking at the patient's immune function (how the body protects itself to prevent and fight infections and diseases). To do this, blood tests will be performed at regular intervals (every 3 to 6 months) for 2 years.

Depending on how well the donor stem cells work in the body after the transplant, the patient may receive one or more Donor Leukocyte Infusions (DLI). This is when leukocytes (a type of white blood cell) collected from the same donor that provided the stem cells are given to the patient through a central line into a vein.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 27

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Stem Cell Transplant	FK506 (Tacrolimus) or Cyclosporine	Total body irradiation (TBI); Fludarabine and Campath 1H; FK506 or Cyclosporine; Stem Cell Transplant; G-CSF.
Stem Cell Transplant	Campath 1H	Total body irradiation (TBI); Fludarabine and Campath 1H; FK506 or Cyclosporine; Stem Cell Transplant; G-CSF.
Stem Cell Transplant	Stem Cell Transplant	Total body irradiation (TBI); Fludarabine and Campath 1H; FK506 or Cyclosporine; Stem Cell Transplant; G-CSF.
Stem Cell Transplant	Fludarabine	Total body irradiation (TBI); Fludarabine and Campath 1H; FK506 or Cyclosporine; Stem Cell Transplant; G-CSF.
Stem Cell Transplant	Total Body Irradiation (TBI)	Total body irradiation (TBI); Fludarabine and Campath 1H; FK506 or Cyclosporine; Stem Cell Transplant; G-CSF.

Primary Outcome Measures

Name	Time	Method
Transplant Related Mortality (TRM)	100 days	Percentage of patients with transplant related mortality

Secondary Outcome Measures

Name	Time	Method
Time in Days to ANC Engraftment	30 days	Engraftment was defined as the day of absolute neutrophil counts (ANC) exceeded 0.5 X 10\^9/L on the first of 3 days.
Donor Chimerism Engraftment of Greater Than 50%	30 days	Number of patients that engrafted who showed a chimerism (donor cells) of greater than 50% in the first 30 days
Acute Graft Versus Host Disease	100 days	Number of patients with Acute Graft Versus Host Disease within 100 days post-transplant
Chronic Graft Versus Host Disease	1 year	Number of patients with Chronic Graft Versus Host Disease within 1 year post-transplant
2-year Relapse-free Survival	2 years	Relapse-free survival (RFS) was calculated from the time of transplant to the date of relapse, death, or last follow-up, whichever occurred first. Survival data were analyzed by Kaplan-Meier method.
2-year Overall Survival	2 years	Overall survival (OS) was calculated from the time of transplant to death from any cause or censored at last follow-up. Survival data were analyzed by Kaplan-Meier method.
Number of Patients Who Engrafted With the Isolex/CLINIMACs System	30 days	Engraftment was defined as the day of absolute neutrophil counts (ANC) exceeded 0.5 X 10\^9/L on the first of 3 days.
Median Time to Engraftment With the Isolex/CLINIMACs System	30 days	Engraftment was defined as the day of absolute neutrophil counts (ANC) exceeded 0.5 X 10\^9/L on the first of 3 days.