A Phase 2 interventional study of Fludarabine monophosphate and Busulfan in Leukemia, Acute Myeloid Leukemia and Acute Lymphocytic Leukemia, sponsored by M.D. Anderson Cancer Center. Completed at 1 site in United States. Open to participants aged 5 Years to 75 Years. Per ClinicalTrials.gov, last updated 2023-06-29.
Sponsored by M.D. Anderson Cancer Center · Phase 2, Interventional, and Treatment
The goal of this clinical research study is to learn if giving busulfan and fludarabine before a stem cell transplant can help control the disease better than the standard method in patients with leukemia, lymphoma, multiple myeloma, MDS, or MPD. In this study, 2 doses of busulfan will be given 2 weeks before a stem cell transplant followed by 4 doses of busulfan and fludarabine during the week before the stem cell transplant, rather than the standard method of giving 4 doses of busulfan and fludarabine only during the week before the stem cell transplant.
The safety of this combination therapy will also be studied.
Busulfan is designed to kill cancer cells by binding to DNA (the genetic material of cells), which may cause cancer cells to die. Busulfan is commonly used in stem cell transplants.
Fludarabine is designed to interfere with the DNA of cancer cells, which may cause the cancer cells to die.
Central Venous Catheter:
If you choose to take part in this study, the chemotherapy, some of the other drugs in this study, and the stem cell transplant will be given by vein through your central venous catheter (CVC). A CVC is a sterile flexible tube and needle that will be placed into a large vein while you are under local anesthesia. Blood samples will also be drawn through your CVC. The CVC will remain in your body during treatment. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form.
Study Drug Administration and Procedures:
For a stem cell transplant, the days before you receive your stem cells are called minus days. The day you receive the stem cells is called Day 0. The days after you receive the stem cells are called plus days.
You will receive a dose of busulfan by vein over about 3 hours on Day -13 and Day -12. With the Day -13 busulfan infusion, about 11 samples of blood (about 1-2 teaspoons each time) will be drawn for pharmacokinetic (PK) testing at various time points before and after you receive your first dose of busulfan. The study staff will tell you the blood testing schedule. PK testing measures the amount of study drug in the body at different time points. The PK testing will help the doctor decide your dose of busulfan for Days -6 through -3. If needed, PK blood testing may also be done on Day -6 during your dose of Busulfan. You may receive the Day -13 and Day -12 busulfan dose either as an outpatient in the clinic or as an inpatient in the hospital.
A heparin lock line will be placed in your vein to lower the number of needle sticks needed for these draws. If it is not possible for the PK tests to be performed for technical reasons, you will be taken off study and receive the standard fixed dose of busulfan.
On Days -13 and -12, you will receive busulfan by vein over 3 hours.
On Days -11 through -7, you will rest.
On Days -6 through -3, you will receive fludarabine by vein over 1 hour, then busulfan by vein over 3 hours.
On Days -2 and -1, you will rest.
On Day 0, you will receive the stem cell transplant by vein.
After the transplant, you will receive tacrolimus, methotrexate, or other drugs to weaken the immune system in the standard manner to lower the risk of graft-vs-host disease (GVHD), a reaction of the donor's immune cells against the recipient's body.
You will receive tacrolimus by vein as a nonstop infusion until you are able to take it by mouth to help lower the risk of GVHD. You will then take tacrolimus by mouth 2 times a day for about 3 months. After that, your tacrolimus dose may be lowered if you do not have GVHD. Your doctor will discuss this with you. On Days 1, 3, and 6, if your stem cells are from a related or matched unrelated donor, you will receive methotrexate over 30 minutes each day by vein to help lower the risk of GVHD. Participants receiving a matched unrelated donor will also receive methotrexate on Day 11 after the transplant.
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.
Study Testing:
While you are in the hospital, you will be checked for any side effects as part of your standard of care. Blood (about 2 teaspoons) will be drawn every day to check for side effects, for routine tests, to check your blood counts, kidney and liver function, and to check for infections.
As part of standard care, you will remain in the hospital for about 3-4 weeks after the transplant. After you are sent home from the hospital, you must remain in the Houston area to be checked for infections and other transplant side effects until about 3 months after transplant. During this time, you will return to the clinic at least 1 time each week. The following tests and procedures will be performed:
About 1, 3, 6, and 12 months after the transplant:
Length of Study:
You will be taken off study 3 years after the end of treatment. You may be taken off study early if the disease gets worse, if you have any intolerable side effects, of if you are unable to follow study directions.
You should talk to the study doctor if you want to leave the study early. If you are taken off study early, you still may need to return for routine follow-up visits after the transplant, if your transplant doctor decides it is needed.
It may be life-threatening to leave the study after you have begun to receive the study drugs but before you receive the stem cells.
This is an investigational study. Busulfan and fludarabine are both FDA approved and commercially available. The investigational part of this study is the addition of 2 more doses of busulfan.
Up to 200 patients will take part in this study. All will be enrolled at MD Anderson.
5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.
This study's enrollment of 201 is above the median of 40 across 4,508 interventional studies indexed under Lymphoma.
Browse Lymphoma 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 administered by vein at dose of 40 mg/m2 in 100 ml of normal saline (NS) on Days -6 through -3. First two doses of Busulfan, 80 mg/m2 administered as an outpatient or as an inpatient to facilitate for this pharmacokinetically directed therapy. Busulfan is administered at the dose calculated to achieve a total (including first two doses delivered on day -13 and -12) systemic exposure of 20,000 ± 12% µMol-min based on the pharmacokinetic studies.
Drug: Fludarabine monophosphate · Drug: Busulfan · Procedure: Stem Cell Infusion · Drug: Tacrolimus · Drug: Methotrexate · Drug: G-CSF
40 mg/m2 by vein on Days -6 through -3.
Also known as: Fludarabine Phosphate, Fludara
First two doses of Busulfan, 80 mg/m2 administered as an outpatient or as an inpatient to facilitate for this pharmacokinetically directed therapy. Busulfan is administered at the dose calculated to achieve a total (including first two doses delivered on day -13 and -12) systemic exposure of 20,000 ± 12% µMol-min based on the pharmacokinetic studies.
Also known as: Busulfex, Myleran
Fresh or cryopreserved bone marrow or peripheral blood progenitor cells infused on Day 0.
Starting dose of 0.015 mg/kg (ideal body weight) as 24 hour continuous infusion daily adjusted to achieve therapeutic level of 5-15 ng/ml. Tacrolimus changed to oral dosing when tolerated and can be tapered off after day +90 if no graft versus host disease (GVHD) present.
Also known as: Prograf
5 mg/m2 by vein on Days 1, 3, 6 and 11 post transplant.
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, Neupogen
Non-Relapse Mortality Rate (NRM)
Number of participants expired within the first 100 days after transplant not due to relapsed disease.
Time frame: 100 days
Overall Survival
Number of participants that are disease free and alive one year post transplant.
Time frame: Up to 1 year post-transplant
Overall Survival
Number of participants that were diseased free and alive 3 years post-transplant.
Time frame: Up to 3 years post-transplant
Participants were recruited from April 2012 to December 2015 at MD Anderson Cancer Center.
| Milestone | Arm 1: Participants w/Hematologic Malignancies Treated w/Fludarabine/TS Busulfan AUC 16,000 Umol/l | Arm 2: Participants w/Hematologic Malignancies Treated w/Fludarabine/TS Busulfan AUC 20,000umol/l. |
|---|---|---|
| Started | 50 | 151 |
| Completed | 49 | 150 |
| Not completed | 1 | 1 |
| Withdrew: Withdrawal by subject | 1 | 0 |
| Withdrew: Physician decision | 0 | 1 |
Number of participants expired within the first 100 days after transplant not due to relapsed disease.
| Participants | Arm 1: Participants w/Hematologic Malignancies Treated w/Fludarabine/TS Busulfan AUC 16,000 Umol/l | Arm 2: Participants w/Hematologic Malignancies Treated w/Fludarabine/TS Busulfan AUC 20,000umol/l. |
|---|---|---|
| Non-Relapse Mortality Rate (NRM) | 2 | 8 |
Number of participants that are disease free and alive one year post transplant.
| Participants | Arm 1: Participants w/Hematologic Malignancies Treated w/Fludarabine/TS Busulfan AUC 16,000 Umol/l | Arm 2: Participants w/Hematologic Malignancies Treated w/Fludarabine/TS Busulfan AUC 20,000umol/l. |
|---|---|---|
| Overall Survival | 29 | 93 |
Number of participants that were diseased free and alive 3 years post-transplant.
| Participants | Arm 1: Participants w/Hematologic Malignancies Treated w/Fludarabine/TS Busulfan AUC 16,000 Umol/l | Arm 2: Participants w/Hematologic Malignancies Treated w/Fludarabine/TS Busulfan AUC 20,000umol/l. |
|---|---|---|
| Overall Survival | 16 | 47 |
Collected over Adverse events were collected up to 3 years post transplant.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm 1: Participants w/Hematologic Malignancies Treated w/Fludarabine/TS Busulfan AUC 16,000 Umol/l | 31/49 (63.3%) | 6/49 (12.2%) | 43/49 (87.8%) |
| Arm 2: Participants w/Hematologic Malignancies Treated w/Fludarabine/TS Busulfan AUC 20,000umol/l. | 93/150 (62%) | 8/150 (5.3%) | 141/150 (94%) |
| Event | Arm 1: Participants w/Hematologic Malignancies Treated w/Fludarabine/TS Busulfan AUC 16,000 Umol/l | Arm 2: Participants w/Hematologic Malignancies Treated w/Fludarabine/TS Busulfan AUC 20,000umol/l. |
|---|---|---|
| Bacterial InfectionsInfections and infestations | 6/49 | 8/150 |
| GI GvHDGastrointestinal disorders | 6/49 | 5/150 |
| Liver GvHDHepatobiliary disorders | 3/49 | 5/150 |
| Skin GvHDSkin and subcutaneous tissue disorders | 2/49 | 6/150 |
| Viral InfectionsInfections and infestations | 2/49 | 4/150 |
| ABO incompatibilityBlood and lymphatic system disorders | 2/49 | 2/150 |
| PneumonitisRespiratory, thoracic and mediastinal disorders | 1/49 | 6/150 |
| Pulmonary edemaRespiratory, thoracic and mediastinal disorders | 1/49 | 0/150 |
| Transcient Secondary graft failureBlood and lymphatic system disorders | 1/49 | 3/150 |
| Delayed engraftmentBlood and lymphatic system disorders | 1/49 | 0/150 |
| Event | Arm 1: Participants w/Hematologic Malignancies Treated w/Fludarabine/TS Busulfan AUC 16,000 Umol/l | Arm 2: Participants w/Hematologic Malignancies Treated w/Fludarabine/TS Busulfan AUC 20,000umol/l. |
|---|---|---|
| MucositisGastrointestinal disorders | 37/49 | 141/150 |
| NauseaGastrointestinal disorders | 43/49 | 119/150 |
| Skin GvHDSkin and subcutaneous tissue disorders | 29/49 | 0/150 |
| Bacterial InfectionsInfections and infestations | 22/49 | 82/150 |
| Fluid overloadGeneral disorders | 25/49 | 81/150 |
| Renal insufficiencyRenal and urinary disorders | 25/49 | 25/150 |
| Viral InfectionsInfections and infestations | 23/49 | 75/150 |
| Elevated transminitisInvestigations | 22/49 | 42/150 |
| Elevated bilirubinInvestigations | 16/49 | 57/150 |
| HypertensionVascular disorders | 11/49 | 51/150 |
| Age, Categorical(Participants) | Arm 1: Participants w/Hematologic Malignancies Treated w/Fludarabine/TS Busulfan AUC 16,000 Umol/l | Arm 2: Participants w/Hematologic Malignancies Treated w/Fludarabine/TS Busulfan AUC 20,000umol/l. | Total |
|---|---|---|---|
| <=18 years | 1 | 0 | 1 |
| Between 18 and 65 years | 37 | 94 | 131 |
| >=65 years | 11 | 56 | 67 |
| Sex: Female, Male(Participants) | Arm 1: Participants w/Hematologic Malignancies Treated w/Fludarabine/TS Busulfan AUC 16,000 Umol/l | Arm 2: Participants w/Hematologic Malignancies Treated w/Fludarabine/TS Busulfan AUC 20,000umol/l. | Total |
|---|---|---|---|
| Female | 13 | 59 | 72 |
| Male | 36 | 91 | 127 |
| Race (NIH/OMB)(Participants) | Arm 1: Participants w/Hematologic Malignancies Treated w/Fludarabine/TS Busulfan AUC 16,000 Umol/l | Arm 2: Participants w/Hematologic Malignancies Treated w/Fludarabine/TS Busulfan AUC 20,000umol/l. | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 3 | 4 | 7 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 2 | 8 | 10 |
| White | 44 | 138 | 182 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Arm 1: Participants w/Hematologic Malignancies Treated w/Fludarabine/TS Busulfan AUC 16,000 Umol/l | Arm 2: Participants w/Hematologic Malignancies Treated w/Fludarabine/TS Busulfan AUC 20,000umol/l. | Total |
|---|---|---|---|
| United States | 49 | 149 | 198 |
| Saudi Arabia | 0 | 1 | 1 |
Documents are hosted by the registry — open the source record to download them.
This study is completed, as verified in Jun 2023. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
M.D. Anderson Cancer Center