Stem Cell Transplant for Hematologic Diseases

NCT ID: NCT00058825

Last Updated: 2016-11-07

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

27 participants

Study Classification

INTERVENTIONAL

Study Start Date

2000-08-31

Study Completion Date

2014-09-30

Brief Summary

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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

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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.

Conditions

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Hematologic Malignancies

Keywords

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Campath stem cell transplant

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Stem Cell Transplant

Total body irradiation (TBI); Fludarabine and Campath 1H; FK506 or Cyclosporine; Stem Cell Transplant; G-CSF.

Group Type EXPERIMENTAL

Campath 1H

Intervention Type BIOLOGICAL

Day -5 to Day -2: Campath 1H dose schedule as per institutional SOP.

Fludarabine

Intervention Type DRUG

Day -5 to Day -2: Fludarabine 30 mg/m2.

Stem Cell Transplant

Intervention Type PROCEDURE

Day 0: Donor stem cells infused.

Total Body Irradiation (TBI)

Intervention Type RADIATION

Day -6: Total body irradiation of 600 cGy as two doses without blocks at a rate of less than or equal to 10 cGy/minute.

FK506 (Tacrolimus) or Cyclosporine

Intervention Type DRUG

Day -2: FK506 or Cyclosporine as medically indicated to prevent GvHD.

Interventions

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Campath 1H

Day -5 to Day -2: Campath 1H dose schedule as per institutional SOP.

Intervention Type BIOLOGICAL

Fludarabine

Day -5 to Day -2: Fludarabine 30 mg/m2.

Intervention Type DRUG

Stem Cell Transplant

Day 0: Donor stem cells infused.

Intervention Type PROCEDURE

Total Body Irradiation (TBI)

Day -6: Total body irradiation of 600 cGy as two doses without blocks at a rate of less than or equal to 10 cGy/minute.

Intervention Type RADIATION

FK506 (Tacrolimus) or Cyclosporine

Day -2: FK506 or Cyclosporine as medically indicated to prevent GvHD.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Diagnosis of myelodysplastic disorders; Fanconi's Anemia; Acute Myelogenous Leukemia (including secondary); Acute Lymphoblastic Leukemia; Multiple Myeloma; Plasma Cell Dyscrasia; lymphoproliferative disorders (Non-Hodgkin Lymphoma, Hairy Cell Leukemia, Chronic Lymphocytic Leukemia, and Hodgkin's Disease). Diagnosis of myelodysplastic disorders which is not good risk by IPSS: Fanconi's Anemia; Acute Myelogenous Leukemia (1st or subsequent relapse, or 2nd or subsequent CR, or refractory disease); Acute Lymphoblastic Leukemia in 2nd or subsequent remission or relapse or refractory disease; Philadelphia Chromosome-positive Chronic Myelogenous Leukemia (failed STI and interferon); Multiple Myeloma (Stage II or III); Lymphoma; Chronic Lymphocytic Leukemia (primary refractory or recurrent disease); Hodgkin's Disease (after relapse); Hemophagocytic Lymphohistiocytosis (failed chemotherapy and/or anti-viral therapy); bone marrow failure such as Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria; PNH (failed prior therapies).
2. Conditions that increase treatment related mortality: (need one or more to be eligible): Age \> / = 50 years; EF of less than 45%; DLCO less than 50% or FEVI 50-75% of predicted value; Diabetes Mellitus; Renal Insufficiency (but creatinine clearance not less than 25 mL/min); Prior recent history of systemic fungal infection; 3rd or greater remission of AML or ALL; Significant Grade III or IV neurologic or hepatic toxicity from previous treatment; More than 1 year from diagnosis (CML or Myeloma patients ONLY); Multiple types of treatment regimens (equal to or more than 3); Significant Grade III or IV neurologic or hepatic toxicity from previous treatment; Prior autologous or allogeneic stem cell transplantation.
3. Haploidentical family member donor. This protocol is open to patients who lack a 5/6 or 6/6 HLA antigen-matched donor. Due to the increased risk of GvHD, patients with Fanconi Anemia and a 5/6 HLA match will also be eligible.

For this protocol, the "best" donor will be defined as a first-degree haploidentical family member who matches at the greatest number of MHC loci. Matching will be determined by Class I and Class II DNA typing. The donor should be sufficiently healthy as to not be at increased risk from the stem cell mobilization procedure. Should more than one "equally" MHC-incompatible donor be identified, other selection criteria will include: age and size of donor, CMV status, and sex. The Principal Investigator will make final decisions.
4. Available healthy donor without any contraindications for donation.
5. Patient and/or legal representative and/or legal guardian able to understand and sign consent.
6. Age between birth and 70 years.
7. Women of child-bearing potential must have a negative pregnancy test.

Exclusion Criteria

1. Pregnant, lactating or unwilling to use contraception.
2. HIV-positive patient.
3. Uncontrolled intercurrent infection.
4. Untreated blast crisis for CML.
5. Uncontrolled high-grade lymphoproliferative disease / lymphoma.
6. Unstable angina and uncompensated congestive heart failure (Zubrod of 3 or greater).
7. Severe chronic pulmonary disease requiring oxygen (Zubrod of 3 or greater).
8. Hemodialysis dependent.
9. Active hepatitis or cirrhosis with total bilirubin, SGOT, and SGPT greater than 3X upper limit of normal.
10. Unstable cerebral vascular disease and recent hemorrhagic stroke (less than 6 months).
11. Active CNS disease from hematological disorder.
Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Methodist Hospital Research Institute

OTHER

Sponsor Role collaborator

Baylor College of Medicine

OTHER

Sponsor Role lead

Responsible Party

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George Carrum

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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George Carrum, MD

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine; The Methodist Hospital

Locations

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Texas Children's Hospital

Houston, Texas, United States

Site Status

The Methodist Hospital

Houston, Texas, United States

Site Status

Countries

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United States

Other Identifiers

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8713-HIMSUM

Identifier Type: -

Identifier Source: org_study_id