The goal of this clinical research study is to learn about the safety of giving a stem cell
transplant from a tissue-mismatched (haploidentical) donor, followed by cyclophosphamide, to
patients with advanced myelofibrosis (MF). Melphalan, fludarabine, and total body irradiation
(TBI) will also be given before the transplant as part of your standard care.
In this study, researchers also want to learn if cyclophosphamide can help to prevent
graft-versus-host disease (GVHD -- when transplanted immune tissue, such as the donor's
tissue, attacks the tissues of the recipient's body).
This is an investigational study. All of the drugs, including TBI, used in this study are FDA
approved and commercially available for the treatment of MF. It is considered part of your
standard care. However, it is investigational to use a haploidentical donor in patients with
The study doctor can explain how the study drugs are designed to work.
Up to 12 participants will be enrolled in this study. All will take part at MD Anderson.
Central Venous Catheter:
The chemotherapy, some of the other drugs in this study, and the stem cell transplant will be
given by vein through a 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. Some 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 Treatment Administration:
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.
On Day -6, you will be admitted to the hospital and given fluids by vein to hydrate you.
On Day -5, you will receive melphalan by vein over 30 minutes and fludarabine by vein over 1
On Days -4 through -2, you will receive fludarabine by vein over 1 hour.
On Day -1, you will receive one dose of TBI. You will receive a separate consent form
describing TBI and its administration in more detail, including its risks.
On Day 0, you will receive the donor's stem cells by vein. This may last anywhere from 15
minutes to several hours.
On Days 3 and 4, you will receive cyclophosphamide by vein over 3 hours. You may also receive
mesna by vein over 30 minutes every 4 hours for a total of 10 mesna doses on Days 3 and 4.
Mesna is given to lower the risk of side effects to the bladder.
Starting on Day 5, you will receive tacrolimus and mycophenolate mofetil (MMF) to help lower
the risk of GVHD. Tacrolimus will be given by vein as a continuous (non-stop) infusion for
about 2 weeks. After the 2 weeks of taking tacrolimus by vein, you will take tacrolimus by
mouth as a pill for at least 3 months. MMF will be given by mouth, 3 times a day, usually
until Day 35.
Starting on Day 7, you will receive filgrastim (G-CSF) 1 time a day as an injection under the
skin, until your blood cell counts reach a high enough level.
As part of your standard care, you will stay in the hospital for about 3-4 weeks after the
transplant. While you are in the hospital, blood (about 2 teaspoons) will be drawn every day
to check for side effects, for routine tests, to check your blood counts, to check your
kidney and liver function, and to check for infections.
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. At each visit,
blood (about 2 teaspoons) will be drawn for routine tests.
At Months 1, 3, 6, 9, and 12, when possible, blood (about 2 teaspoons) will be drawn to check
your immune system function.
At Months 1, 3, 6, 12, and 24, you will also have a bone marrow aspiration and/or blood
(about 2 teaspoons) will be drawn to check the status of the disease. To collect a bone
marrow aspirate, an area of the hip or other site is numbed with anesthetic, and a small
amount of bone marrow is withdrawn through a large needle.
If the study doctor thinks it is needed based on side effects you may be having, additional
follow-up tests will be performed.
Length of Study Participation:
You will be on this study for up to about 2 years. You will be taken off study if the disease
gets worse. The study drugs will be stopped if intolerable side effects occur.
1. Diagnosis of primary or secondary Myelofibrosis with transplant indication by
DIPSS-plus (> intermediate -1);
2. Age 18-70; patients >/= age 50 must have an comorbidity score (HCT-CI) </= 4 (Sorror).
The Principal Investigator is the final arbiter for comorbidity;
3. Patients can be in chronic phase (CP) with BM blast count </= 10% or after progression
to AML and achieved </= 5% BM blasts (morphologic CR prior to transplant);
4. Lack of an HLA matched donor or need to proceed fast to transplantation when a patient
does not have an immediately available matched unrelated donor (typed by
high-resolution in the registry);
5. Performance status >/=70% (Karnofsky); patients > 50 years should have adequate
cognitive function; any concerns regarding cognitive function should be addressed by a
6. Adequate organ function: ALT/AST/bilirubin </= 5X UNL, creatinine clearance >
50mls/min (calculated with Cockcroft-Gault formula); LVEF >/= 50%, DLCOc >/= 50%;
7. Prior treatment with JAK2 inhibitor therapy is not excluded. Patients on a JAK2
inhibitor may continue through conditioning until Day -3 then tapered at the
discretion of the investigator.
1. Evidence of portal hypertension with varices, ascites, or hepatic encephalopathy;
2. >10% bone marrow blasts at transplant if no history of AML and >5% if had previous
progression to AML;
3. HIV positive; active hepatitis B or C;
4. Patients with active infections. The PI is the final arbiter of the eligibility;
5. Liver cirrhosis;
6. Prior CNS involvement by tumor cells;
7. Severe pulmonary hypertension (PHT) (On echo or right side cardiac catheterization);
8. History of another primary malignancy that has not been in remission for at least 3
years (the following are exempt from the 3-year limit: non-melanoma skin cancer, fully
excised melanoma in situ [Stage 0], curatively treated localized prostate cancer, and
cervical or breast carcinoma in situ on biopsy or a squamous intraepithelial lesion on
9. Positive Beta HCG test in a woman with child bearing potential defined as not
post-menopausal for 12 months or no previous surgical sterilization;
10. Noncompliance - Inability or unwillingness to comply with medical recommendations
regarding therapy or follow-up, including smoking tobacco. Smoking cessation is a
standard teaching practice prior to admission for all patients undergoing stem cell
transplant. Any patient who refuses to stop smoking prior to transplant will not be
eligible for this study.