Hematologic Malignancies
Conditions
Keywords
Campath, stem cell transplant
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.
Interventions
BIOLOGICALCampath 1H
Day -5 to Day -2: Campath 1H dose schedule as per institutional SOP.
DRUGFludarabine
Day -5 to Day -2: Fludarabine 30 mg/m2.
PROCEDUREStem Cell Transplant
Day 0: Donor stem cells infused.
RADIATIONTotal 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.
DRUGFK506 (Tacrolimus) or Cyclosporine
Day -2: FK506 or Cyclosporine as medically indicated to prevent GvHD.
Sponsors
The Methodist Hospital Research Institute
Baylor College of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Transplant Related Mortality (TRM) | 100 days | Percentage of patients with transplant related mortality |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
| 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. |
| 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. |
| Chronic Graft Versus Host Disease | 1 year | Number of patients with Chronic Graft Versus Host Disease within 1 year post-transplant |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Stem Cell Transplant Total body irradiation (TBI); Fludarabine and Campath 1H; FK506 or Cyclosporine; Stem Cell Transplant; G-CSF.
Campath 1H: Day -5 to Day -2: Campath 1H dose schedule as per institutional SOP.
Fludarabine: Day -5 to Day -2: Fludarabine 30 mg/m2.
Stem Cell Transplant: Day 0: Donor stem cells infused.
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.
FK506 (Tacrolimus) or Cyclosporine: Day -2: FK506 or Cyclosporine as medically indicated to prevent GvHD. | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 3 |
| Overall Study | Graft Failure | 5 |
| Overall Study | Progressive Disease | 5 |
| Overall Study | Relapse | 9 |
Baseline characteristics
| Characteristic | Stem Cell Transplant |
|---|---|
| Age, Continuous | 15 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 19 / 27 |
| serious Total, serious adverse events | 4 / 27 |
Outcome results
Primary
Transplant Related Mortality (TRM)
Percentage of patients with transplant related mortality
Time frame: 100 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stem Cell Transplant | Transplant Related Mortality (TRM) | 0 percentage of participants |
Secondary
2-year Overall Survival
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.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stem Cell Transplant | 2-year Overall Survival | 33.3 percentage of participants |
Secondary
2-year Relapse-free Survival
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.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stem Cell Transplant | 2-year Relapse-free Survival | 25.9 percentage of participants |
Secondary
Acute Graft Versus Host Disease
Number of patients with Acute Graft Versus Host Disease within 100 days post-transplant
Time frame: 100 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stem Cell Transplant | Acute Graft Versus Host Disease | Grade II | 0 participants |
| Stem Cell Transplant | Acute Graft Versus Host Disease | Grade III | 1 participants |
| Stem Cell Transplant | Acute Graft Versus Host Disease | Grade IV | 0 participants |
| Stem Cell Transplant | Acute Graft Versus Host Disease | Grade 0 | 26 participants |
| Stem Cell Transplant | Acute Graft Versus Host Disease | Grade I | 0 participants |
Secondary
Chronic Graft Versus Host Disease
Number of patients with Chronic Graft Versus Host Disease within 1 year post-transplant
Time frame: 1 year
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stem Cell Transplant | Chronic Graft Versus Host Disease | Yes | 1 participants |
| Stem Cell Transplant | Chronic Graft Versus Host Disease | No | 26 participants |
Secondary
Donor Chimerism Engraftment of Greater Than 50%
Number of patients that engrafted who showed a chimerism (donor cells) of greater than 50% in the first 30 days
Time frame: 30 days
Population: Patients engrafted
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stem Cell Transplant | Donor Chimerism Engraftment of Greater Than 50% | Yes | 20 participants |
| Stem Cell Transplant | Donor Chimerism Engraftment of Greater Than 50% | No | 2 participants |
Secondary
Median Time to Engraftment With the Isolex/CLINIMACs System
Engraftment was defined as the day of absolute neutrophil counts (ANC) exceeded 0.5 X 10\^9/L on the first of 3 days.
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stem Cell Transplant | Median Time to Engraftment With the Isolex/CLINIMACs System | 12 days |
| CLINIMACs | Median Time to Engraftment With the Isolex/CLINIMACs System | 12 days |
Secondary
Number of Patients Who Engrafted With the Isolex/CLINIMACs System
Engraftment was defined as the day of absolute neutrophil counts (ANC) exceeded 0.5 X 10\^9/L on the first of 3 days.
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stem Cell Transplant | Number of Patients Who Engrafted With the Isolex/CLINIMACs System | 15 participants |
| CLINIMACs | Number of Patients Who Engrafted With the Isolex/CLINIMACs System | 7 participants |
Secondary
Time in Days to ANC Engraftment
Engraftment was defined as the day of absolute neutrophil counts (ANC) exceeded 0.5 X 10\^9/L on the first of 3 days.
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stem Cell Transplant | Time in Days to ANC Engraftment | 12 days |