Lymphoma, Disorder Related to Bone Marrow Transplantation
Conditions
Keywords
Cutaneous T-Cell Lymphoma, CTCL, Allogeneic Transplantation, Lymphoma, Allogeneic peripheral blood progenitor cell, PBPC, Bone Marrow transplantation, Stem Cell Transplant, SCT, Fludarabine, Fludarabine Phosphate, Fludara, Melphalan
Brief summary
The goal of this clinical research study is to see if receiving a transplant of blood stem cells (cells that can produce blood) or bone marrow from either a related donor (brother, sister or other relative) or an unrelated voluntary donor will help patients with advanced cutaneous T-cell lymphoma. The length of time that patients who receive the treatment remain free of disease will also be studied.
Detailed description
You will receive the chemotherapy drug fludarabine for 5 days (Days 1 to 5). The drug melphalan will be given on Days 4 and 5. You may also receive the drug anti-thymocyte globulin (ATG) on Days 4, 5, 6. This will be followed by infusion of blood stem cells or bone marrow from a donor on Day 7. A separate consent will be provided to the donor. The donor can be a brother, sister or another family member or a compatible unrelated donor. The drugs and the stem cells will be given through a catheter (a small tube) placed under the collarbone. You may receive your treatment on an inpatient or outpatient basis. If treated on an inpatient basis, you will stay in the hospital during treatment and recovery, which can take 4 to 5 weeks even if there are no complications. The chemotherapy and the ATG are given to help the body accept the transplanted stem cells or bone marrow. You will receive antibiotics to fight infection and a medicine called G-CSF (Neupogen®) to help blood counts rise back to healthier levels. G-CSF is given as an injection under the skin. You will also need blood and platelet transfusions. You will be given standard drugs to help decrease the risk of side effects. You may ask the study staff for information about how the drugs are given and their risks. If the cancer grows and graft-versus-host disease is not present, you may be eligible to receive donor blood cells (lymphocytes) infused through the catheter. This may cause graft-versus-host disease and may help shrink the cancer. If the cancer grows and graft-versus-host disease is already present, then donor lymphocytes are not given. Sometimes, the body rejects the donor cells; this reaction is called graft rejection. Sometimes the donor cells attack the body, a reaction called graft-versus-host disease (GvHD). The drugs tacrolimus and methotrexate will be given to help prevent these reactions from occurring. These drugs are given through a vein or by mouth before and/or after the transplant. You must stay in the Houston area for at least 100 days after the transplant. After 100 days, you must return to Houston every 3 months for 2 years for tests and checkups, then once a year for at least 3 years. If there is no sign of lymphoma growth at the follow up visit(s), you will receive no further treatment. This is an investigational study. The drugs used in this study are approved by the FDA and are commercially available. As many as 35 patients will take part in the study. All will be enrolled at MD Anderson.
Interventions
DRUGFludarabine
25 mg/m\^2 Given By Vein Daily for 5 Days Prior to Allogeneic Transplant.
DRUGMelphalan
70 mg/m\^2 Given By Vein Daily for 2 Days Prior to Allogeneic Transplant.
PROCEDUREAllogeneic Transplant
Allogeneic transplant given by vein after completion of Fludarabine and Melphalan.
DRUGThymoglobulin
2 mg/kg/day by vein on days -3, -2 and -1 for patients receiving matched unrelated marrow/stem cells or mismatched related marrow.
Sponsors
M.D. Anderson Cancer Center
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. Patients with pathologically proven cutaneous T-cell lymphoma (CTCL), disease stage IIB to IVB, patients must be in at least a partial response-PR (skin and lymph nodes) after receiving other non-allogeneic transplant therapy, age \</= 70 years, Zubrod performance status 0 or 1, left ventricular ejection fraction \>/= 50% or approved for transplant by a cardiologist, DLCO \>/= 50% predicted or approved for transplant by a pulmonologist, serum creatinine \</= 1.5 mg/dL, serum bilirubin \< 2mg/dL. SGPT \< 3 x upper limit of normal, and no previous history of allogeneic transplantation. 2. Donor: HLA-compatible related (HLA-A, -B, -DRB1 matched or with one-antigen mismatch) or HLA-compatible unrelated (HLA-A, -B, -C and -DRB1 matched or with one-antigen mismatch).
Exclusion criteria
1\) Patients cannot have active central nervous system (CNS) disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participant's Response According to Physician's Global Assessment of Clinical Condition (PGA) | Response assessed pre-transplant and 100 days post transplant with follow up at 1 year. | Response defined by Physician's Global Assessment of Clinical Condition (PGA) where Complete Response (CR) is No evidence of disease; 100% improvement; Partial Response (PR), one of following: 1) Very significant clearance ( \> 90% to \< 100%); only traces of disease remains; 2) Significant improvement ( \> 75% to \< 90%); some evidence of disease remain; 3) Intermediate between slight and marked improvement; ( \> 50% to \< 75%); 4) Some improvement ( \> 25% to \< 50%); however, significant evidence of disease remains; Stable Disease (SD): Disease has not changed from baseline condition (+\<25%); Progressive Disease (PD): Disease is worse than at baseline evaluation by \> 25% or more. Response confirmed by a second assessment at least 4 weeks following it. Assessments at baseline, pre and post transplant (100 days) then till disease progression or year one. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Overall Survival (OS) Length | Baseline to disease progression, followed up to 5 years post transplant | OS was defined as the time from transplantation to the date of death from any cause or last follow up, measured in days. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: September 26, 2003 to November 05, 2012. All recruitment done at The University of Texas MD Anderson Cancer Center.
Participants by arm
| Arm | Count |
|---|---|
| Fludarabine + Melphalan With PBPC Fludarabine 25 mg/m\^2 intravenous (IV) daily for 5 days prior to allogeneic peripheral blood progenitor cell (PBPC) , Melphalan 70 mg/m\^2 IV daily for 2 days prior to IV Allogeneic Transplant following Fludarabine & Melphalan. Thymoglobulin 2 mg/kg/day IV on days -3, -2 & -1 for patients receiving matched unrelated marrow/stem cells or mismatched related marrow. | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 7 |
| Overall Study | Disease Progression/Relapse | 15 |
Baseline characteristics
| Characteristic | Fludarabine + Melphalan With PBPC |
|---|---|
| Age, Continuous | 55 years |
| Region of Enrollment United States | 33 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 33 / 33 |
| serious Total, serious adverse events | 0 / 33 |
Outcome results
Primary
Participant's Response According to Physician's Global Assessment of Clinical Condition (PGA)
Response defined by Physician's Global Assessment of Clinical Condition (PGA) where Complete Response (CR) is No evidence of disease; 100% improvement; Partial Response (PR), one of following: 1) Very significant clearance ( \> 90% to \< 100%); only traces of disease remains; 2) Significant improvement ( \> 75% to \< 90%); some evidence of disease remain; 3) Intermediate between slight and marked improvement; ( \> 50% to \< 75%); 4) Some improvement ( \> 25% to \< 50%); however, significant evidence of disease remains; Stable Disease (SD): Disease has not changed from baseline condition (+\<25%); Progressive Disease (PD): Disease is worse than at baseline evaluation by \> 25% or more. Response confirmed by a second assessment at least 4 weeks following it. Assessments at baseline, pre and post transplant (100 days) then till disease progression or year one.
Time frame: Response assessed pre-transplant and 100 days post transplant with follow up at 1 year.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fludarabine + Melphalan With PBPC | Participant's Response According to Physician's Global Assessment of Clinical Condition (PGA) | Complete Response (CR) Converted Post Transplant | 19 participants |
| Fludarabine + Melphalan With PBPC | Participant's Response According to Physician's Global Assessment of Clinical Condition (PGA) | CR Prior to Transplant | 6 participants |
| Fludarabine + Melphalan With PBPC | Participant's Response According to Physician's Global Assessment of Clinical Condition (PGA) | Partial Response (PR) | 0 participants |
| Fludarabine + Melphalan With PBPC | Participant's Response According to Physician's Global Assessment of Clinical Condition (PGA) | Stable Disease (SD) | 0 participants |
| Fludarabine + Melphalan With PBPC | Participant's Response According to Physician's Global Assessment of Clinical Condition (PGA) | Progressive Disease (PD) | 16 participants |
Secondary
Average Overall Survival (OS) Length
OS was defined as the time from transplantation to the date of death from any cause or last follow up, measured in days.
Time frame: Baseline to disease progression, followed up to 5 years post transplant
Population: Baseline to disease progression, followed up to 5 years post transplant (assess at 100 days, every 3 months for 2 years, then once a year for at least 3 years)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Fludarabine + Melphalan With PBPC | Average Overall Survival (OS) Length | 1207 Days |