A Phase 2 interventional study of Fludarabine and Melphalan in Leukemia, Lymphoma and Myeloma, sponsored by M.D. Anderson Cancer Center. Terminated at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2016-03-17.
Sponsored by M.D. Anderson Cancer Center · Phase 2, Interventional, and Treatment
The goal of this clinical research study is to learn what dose of a kind of immune cell called T-lymphocytes (T-cells) given as a donor infusion about 8-9 weeks after a stem cell transplant has the best results. The safety of this treatment will also be studied. This will be tested in patients with leukemia, MDS, lymphoma, Hodgkin disease, and multiple myeloma. These results are measured as helping to control the disease without severe graft-versus-host disease (GvHD). GvHD is when transplanted donor tissue attacks the tissues of the recipient's body.
Fludarabine, melphalan, and alemtuzumab are commonly given before stem cell transplants:
The donor infusion of T-cells is designed to help restore the immune system after the transplant, cause an immune reaction against the cancer, and reduce the risk of the cancer coming back.
Study Groups:
If you agree to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups involving the dose of T-cells in the donor lymphocyte infusion.
Both you and your study doctor will know which group you are in. Both groups will have a stem cell transplant. The stem cells will be given by vein. The cells will travel to your bone marrow where they are designed to make healthy, new blood cells after several weeks.
Study Drug Administration:
Patients receive fludarabine, melphalan and alemtuzumab to kill malignant cells and suppress immunity to prevent rejection of the stem cell transplant. The day you receive the stem cells is called Day 0. The days before you receive your stem cells are called minus days. The days after you receive the stem cells are called plus days.
On Day -7, you will be admitted to the hospital and given fluids by vein to hydrate you.
On Days -6 through -3, you will receive fludarabine by vein over 1 hour each day.
On Day -2, you will receive melphalan by vein over 30 minutes.
On Day -1, you will receive alemtuzumab by vein over 2 hours.
On Day 0, you will receive the stem cell transplant as a cell infusion by vein.
After the transplant, you will receive tacrolimus and methotrexate. At first, you will receive tacrolimus as a continuous (nonstop) infusion until you are able to take it by mouth. You will then take tacrolimus by mouth 2 times a day for about 5 weeks and then your doctor will tell you how to taper it off (gradually stop taking it). On Days 1, 3, and 6 after the transplant, you will receive methotrexate by vein over 30 minutes.
You will receive filgrastim as an injection under the skin 1 time a day, starting 1 week after the transplant, until your blood cell levels return to normal. Filgrastim is designed to help with the growth of white blood cells.
Between Day +56 and +64, if you are in stable medical condition and have not developed GvHD, you will receive a donor lymphocyte infusion containing T-cells by vein over 10-30 minutes. You will receive Benadryl (diphenhydramine) by vein over 15 minutes before the infusion to lower the risk of an allergic reaction.
Study Visits:
Before the T-cell infusion:
After the T-cell infusion, you will have a physical exam every week for at least 6 weeks.
About 3, 6, and 12 months after the transplant:
During the study, you will have blood draws (about 2 teaspoons) and urine will be collected for routine tests, to check your blood counts, kidney and liver function, and/or to check for infections as often as the doctor thinks is needed during this time.
Length of Treatment:
You will be off study after your 12-month follow-up visit. You will be taken off study early if you have graft failure (the donor cells did not "take") or if the cancer comes back and needs another treatment.
This is an investigational study. Melphalan, fludarabine, and alemtuzumab are FDA approved and commercially available for the treatment of blood cancers. Donor T-cell infusions are commonly used to treat blood cancers that come back after a stem cell transplant. The investigational part of this study is to find the best dose of T-cells that are given with the goal of helping to prevent the cancer from coming back.
Up to 56 patients will take part in this study. All will be enrolled at MD Anderson.
626 studies on the registry are indexed under Myeloproliferative Disorders; 109 are open to participants now.
This study's enrollment of 16 is below the median of 45 across 439 interventional studies indexed under Myeloproliferative Disorders.
Browse Myeloproliferative Disorders studies →M.D. Anderson Cancer Center is the lead sponsor of 2,999 studies on the registry; 581 are open to participants now.
Of its 599 completed or terminated interventional studies of FDA-regulated products, 402 (67%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Fludarabine 40 mg/m\^2 by vein on Day -6 to -3. Melphalan 140 mg/m\^2 by vein on Day -2. Alemtuzumab 50 mg by vein on Day -1. Reduced intensity stem cell transplant on Day 0. Planned Donor Lymphocyte Infusion CD3+ cells: 3 \* 106 CD3+ cells/kg between Day +56 and +64. Tacrolimus 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35. Methotrexate 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is \> 500 \* 10/L for 3 consecutive days.
Drug: Fludarabine · Drug: Melphalan · Drug: Alemtuzumab · Procedure: Stem Cell Infusion · Drug: Tacrolimus · Drug: Methotrexate · Drug: G-CSF · Procedure: Low Dose Donor T-Cells
Fludarabine 40 mg/m\^2 by vein on Day -6 to -3. Melphalan 140 mg/m\^2 by vein on Day -2. Alemtuzumab 50 mg by vein on Day -1. Reduced intensity stem cell transplant on Day 0. High Dose Donor T-Cells Planned Donor Lymphocyte Infusion CD3+ cells: 1 \* 107 CD3+ cells/kg between Day +56 and +64. Tacrolimus 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35. Methotrexate 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is \> 500 \* 10/L for 3 consecutive days.
Drug: Fludarabine · Drug: Melphalan · Drug: Alemtuzumab · Procedure: Stem Cell Infusion · Drug: Tacrolimus · Drug: Methotrexate · Drug: G-CSF · Procedure: High Dose Donor T-Cells
40 mg/m\^2 by vein on Day -6 to -3.
Also known as: Fludarabine Phosphate, Fludara
140 mg/m\^2 by vein on Day -2.
Also known as: Alkeran
50 mg by vein on Day -1.
Also known as: CAMPATH-1H, Campath
Reduced intensity stem cell transplant on Day 0.
0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35.
Also known as: Prograf
5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6.
5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is \> 500 \* 10/L for 3 consecutive days.
Also known as: Filgrastim, NeupogenTM
Planned Donor Lymphocyte Infusion CD3+ cells: 3 \* 106 CD3+ cells/kg between Day +56 and +64.
Planned Donor Lymphocyte Infusion CD3+ cells: 1 \* 107 CD3+ cells/kg between Day +56 and +64.
Success Rate
Success rate defined as alive, engrafted without grade 3 or 4 GvHD or relapse at day 100 post allogeneic stem cell transplantation followed by donor lymphocyte infusion (DLI).
Time frame: 100 days
Overall Survival (OS)
Overall Survival is defined as the interval between day of transplant and day of death.
Time frame: Every 3 months until day of death
Recruitment Period: February 6, 2012 to February 27, 2014. All recruitment done at The University of Texas (UT) MD Anderson Cancer Center.
| Milestone | Stem Cell Infusion | Low Dose Donor T-Cells | High Dose Donor T-Cells |
|---|---|---|---|
| Started | 16 | 0 | 0 |
| Completed | 7 | 0 | 0 |
| Not completed | 9 | 0 | 0 |
| Withdrew: Active graft-vs-host disease (gvhd) | 5 | 0 | 0 |
| Withdrew: Death | 2 | 0 | 0 |
| Withdrew: Secondary graft failure | 1 | 0 | 0 |
| Withdrew: Adverse event | 1 | 0 | 0 |
| Milestone | Stem Cell Infusion | Low Dose Donor T-Cells | High Dose Donor T-Cells |
|---|---|---|---|
| Started | 0 | 3 | 4 |
| Completed | 0 | 1 | 3 |
| Not completed | 0 | 2 | 1 |
| Withdrew: Death | 0 | 2 | 1 |
Success rate defined as alive, engrafted without grade 3 or 4 GvHD or relapse at day 100 post allogeneic stem cell transplantation followed by donor lymphocyte infusion (DLI).
| participants | Low Dose Donor T-Cells | High Dose Donor T-Cells |
|---|---|---|
| Success Rate | 1 | 3 |
Overall Survival is defined as the interval between day of transplant and day of death.
| days | Stem Cell Transplant + Donor Lymphocyte Infusion |
|---|---|
| Overall Survival (OS) | 246 (26 to 504) |
Collected over Adverse events (AEs) were collected from the start of preparative regimen up to discontinuation of study treatment. Overall collection period: March 30, 2012 to April 15, 2014.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Stem Cell Infusion | — | 9/9 (100%) | 9/9 (100%) |
| Low Dose Donor T-Cells | — | 2/3 (66.7%) | 3/3 (100%) |
| High Dose Donor T-Cells | — | 4/4 (100%) | 4/4 (100%) |
| Event | Stem Cell Infusion | Low Dose Donor T-Cells | High Dose Donor T-Cells |
|---|---|---|---|
| Liver GvHDHepatobiliary disorders | 0/9 | 1/3 | 3/4 |
| DeathGeneral disorders | 5/9 | 2/3 | 1/4 |
| PneumoniaRespiratory, thoracic and mediastinal disorders | 3/9 | 0/3 | 0/4 |
| Respiratory Syncytial Virus Upper Respiratory IllnessRespiratory, thoracic and mediastinal disorders | 1/9 | 1/3 | 0/4 |
| Secondary Graft FailureImmune system disorders | 1/9 | 0/3 | 1/4 |
| Deep Vein ThrombosisBlood and lymphatic system disorders | 0/9 | 0/3 | 1/4 |
| Pneumocystis Jiroveci (PCP) PneumoniaRespiratory, thoracic and mediastinal disorders | 0/9 | 0/3 | 1/4 |
| Fusarium PneumoniaRespiratory, thoracic and mediastinal disorders | 0/9 | 0/3 | 1/4 |
| Pulmonary NocardiosisRespiratory, thoracic and mediastinal disorders | 0/9 | 0/3 | 1/4 |
| Pseudomonas PneumoniaRespiratory, thoracic and mediastinal disorders | 0/9 | 0/3 | 1/4 |
| Event | Stem Cell Infusion | Low Dose Donor T-Cells | High Dose Donor T-Cells |
|---|---|---|---|
| NauseaGastrointestinal disorders | 9/9 | 3/3 | 4/4 |
| Cytomegalovirus ReactivationInfections and infestations | 3/9 | 3/3 | 3/4 |
| Skin GvHDSkin and subcutaneous tissue disorders | 5/9 | 2/3 | 3/4 |
| Upper Gastrointestinal GvHDGastrointestinal disorders | 1/9 | 0/3 | 3/4 |
| Fluid OverloadMetabolism and nutrition disorders | 6/9 | 0/3 | 0/4 |
| Elevated Alanine AminotransferaseMetabolism and nutrition disorders | 2/9 | 2/3 | 2/4 |
| DiarrheaGastrointestinal disorders | 4/9 | 1/3 | 2/4 |
| Gastrointestinal GvHDGastrointestinal disorders | 2/9 | 0/3 | 2/4 |
| Liver GvHDHepatobiliary disorders | 0/9 | 0/3 | 2/4 |
| MucositisGastrointestinal disorders | 4/9 | 1/3 | 1/4 |
| Age, Continuous(years) | Stem Cell Transplant + Donor Lymphocyte Infusion |
|---|---|
| Median | 58 (35 to 65) |
| Sex: Female, Male(Participants) | Stem Cell Transplant + Donor Lymphocyte Infusion |
|---|---|
| Female | 5 |
| Male | 11 |
| Region of Enrollment(participants) | Stem Cell Transplant + Donor Lymphocyte Infusion |
|---|---|
| United States | 16 |
This study is terminated, as verified in Feb 2016. You cannot join it, but the record below documents what was studied.
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M.D. Anderson Cancer Center