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Three-arm Clinical Trial for Patients With Hematologic Malignancies and Mismatched Donors - Haploidentical, 1 Antigen Mismatch Related or Unrelated, and Matched Unrelated Donor (MUD)- Using a T-cell Replete Allograft and High-dose Post-transplant Cyclophosphamide

Phase 2
65 Years
Open (Enrolling)
Blood Stem Cell Transplant Failure, Leukemia, Hematologic Malignancies

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Trial Information

Three-arm Clinical Trial for Patients With Hematologic Malignancies and Mismatched Donors - Haploidentical, 1 Antigen Mismatch Related or Unrelated, and Matched Unrelated Donor (MUD)- Using a T-cell Replete Allograft and High-dose Post-transplant Cyclophosphamide

The Study Treatment:

Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may
slow or stop their growth and spread throughout the body. This may cause the cancer cells
to die.

In this study, researchers want to learn if cyclophosphamide can help to prevent
graft-versus-host disease (GVHD -- when transplanted immune tissue, such as white blood
cells, attacks the tissues of the recipient's body).

Melphalan, thiotepa, and fludarabine are commonly used in combination with a stem cell

Study Treatment Administration:

If you are found to be eligible to take part in this study, you will receive chemotherapy
for 6 days:

- You will receive melphalan by vein over 30 minutes on Day -8 (8 days before the

- You will receive thiotepa by vein over 4 hours on Day -7.

- You will receive fludarabine by vein over 1 hour on Days -6, -5, -4, and -3.

If thiotepa is not available, you will receive melphalan by vein over 30 minutes on Day -6
and fludarabine by vein over 1 hour on Days -5, -4, -3, and -2. You may receive total body
irradiation (TBI) on Day -1, if your doctor thinks it is needed.

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 will 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 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

Starting on Day 7, you will receive filgrastim (G-CSF) once a day as an injection under the
skin, until your blood cell counts reach a high enough level.

Depending on the type of disease that you have, your doctor may decide to give you rituximab
by vein over several hours on Days -13, -6, 1, and 8. Rituximab is given to help the body
get rid of abnormal white blood cells.

Length of Study Participation:

You will be in the hospital for about 4 weeks after the transplant. You will be taken off
study if the disease gets worse. The study drugs will be stopped if intolerable side
effects occur.

Follow-Up Visits:

You will be asked to stay close enough to Houston to be able to come back for any visits for
at least 100 days after the transplant.

At 1, 3, 6, and 12 months after the transplant, the following tests and procedures will be

- You will have a physical exam.

- Blood (about 4 tablespoons) will be drawn for routine tests.

- You will have a bone marrow biopsy to check the status of the disease.

- Blood (about 4 tablespoons) will be drawn to measure tumor cells and to predict graft
failure and/or relapse.

- You may have urine collected and/or scans performed such as x-rays, CT scans, and/or a
positron emission tomography (PET) scan. These scans and urine tests would only be
done if the study doctor thinks they are needed to check the status of the disease.

- Blood (about 4 tablespoons) will be drawn to check your immune system.

If you have AML, at 2 months after the transplant, blood (about 4 tablespoons) will be drawn
to check your immune system.

If you have MM, you will have a bone survey once a year.

If the study doctor thinks it is needed based on side effects you may be having, additional
follow-up tests will be performed.

You may be contacted by phone 1-2 times a year to ask about the status of the disease. These
calls will take about 10 minutes to complete.

This is an investigational study. All of the drugs used in this study are commercially
available and FDA approved. However, it is investigational to give high-dose
cyclophosphamide for preventing GVHD that may occur after a stem cell transplant from a
tissue-mismatched donor.

Up to 213 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Patients < 55 years (Myeloablative regimen 1) or >/ = 55 and intensity regimen 2) old lacking a matched related volunteer donor identified in time
for transplant for which a related haploidentical donor ( A, B, C, DR loci), a 7/8 allele matched related or unrelated donor is identified, or
a matched unrelated donor (MUD) .

2. Acute lymphocytic leukemia (ALL) in CR1 with high-risk features including adverse
cytogenetics such as t(9;22), t(1;19), t(4;11), or MLL gene rearrangements; ALL in
second or greater remission or ALL with relapsed disease, peripheral blood blasts <
1000/microliter, ALL patients must show response to most recent received

3. Acute myeloid leukemia (AML) in CR1 with intermediate-risk disease or high-risk
features defined as: Greater than 1 cycle of induction therapy required to achieve
remission; Preceding myelodysplastic syndrome (MDS) or myeloproliferative disease;
Presence of FLT3 mutations or internal tandem duplications; FAB M6 or M7
classification; Adverse cytogenetics, -5, del 5q, -7, del7q, abnormalities involving
3q, 9q, 11q, 20q, 21q, 17, +8 [> 3 abnormalities], peripheral blood blasts
<1000/microliter, AML patients must show response to most recent received

4. AML in second or greater remission, primary induction failure and patients with
relapsed disease, peripheral blood blasts <1000/microliter;

5. Myelodysplastic syndrome (MDS) with International Prognostic Scoring System (IPSS)
intermediate-2 or higher; or therapy-related MDS

6. Aplastic anemia with Absolute neutrophil count (ANC)<1000 and transfusion dependent
after they failed immunosuppression therapy

7. Chronic myeloid leukemia (CML) >/=1st chronic phase, after failed >/=2 lines of
tyrosine kinase inhibitors; in accelerated or blast phase with > 30% bone marrow

8. Prior allogeneic stem cell transplant more than 6 months from the first transplant,
in remission.

9. Chemotherapy-sensitive relapsed lymphoma (Complete or partial response), Hodgkin's or
non-Hodgkin's lymphoma, no evidence of "bulky" disease (> 10 cm in diameter);

10. Patients with chemo-sensitive CLL with persistent or recurrent disease after
fludarabine-based regimens, no evidence of "bulky" disease (> 10 cm in diameter)

11. Patients with poor prognosis multiple myeloma by cytogenetics (del13, del 17p,
t(1;14) or t(14;16) or hypodiploidy, with advanced disease (stage>/=2) and /or
relapsed after autologous stem cell transplant.

12. Patients with myelofibrosis (Lille >0, transfusion dependency, progression to blast
phase; however, in remission from AML) or CMML. These patients will be treated with
the reduced-intensity conditioning regimen (with melphalan 100mg/m2 and thiotepa 5
mg/kg regimen) and will be subject to the same stopping rule as the group >/= 55
years or with comorbidities.

13. Zubrod performance status 0-1 or Lansky PS greater or equal to 70%.

14. Available donor able to undergo a bone marrow harvest. For matched unrelated donor
transplants only: Peripheral blood stem cells may be collected if donor is
unavailable for bone marrow harvest or if adequate bone marrow cannot be collected.

15. Bilirubin
16. Serum creatinine clearance >/=50 ml/min (calculated with Cockroft-Gault formula);
Creatinine for children (whichever is less);

17. Diffusing capacity for carbon monoxide (DLCO) >/= 45% predicted corrected for
hemoglobin. For pediatric patients, if unable to perform pulmonary function, >/= 92%
oxygen saturation with pulse oximetry.

18. LVEF >/= 40%.

19. Patient or patient's legal representative, parent(s) or guardian should provide
written informed consent. Assent of a minor if participant's age is at least seven
and less than eighteen years.

Exclusion Criteria:

1. HIV positive; active hepatitis B or C

2. Patients with active infections. The PI is the final arbiter of the eligibility.

3. Liver cirrhosis with greater than grade 1 stage 1 inflammation/fibrosis

4. Uncontrolled CNS involvement by tumor cells

5. 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: nonmelanoma skin cancer,
fully excised melanoma in situ [Stage 0], curatively treated localized prostate
cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion
on PAP smear.)

6. Positive Beta HCG test in a woman with child bearing potential defined as not
post-menopausal for 12 months or no previous surgical sterilization.

7. Inability to comply with medical therapy or follow-up

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Non-relapse Mortality (NRM)

Outcome Time Frame:

At 100 days

Safety Issue:


Principal Investigator

Stefan Ciurea, MD

Investigator Role:

Study Chair

Investigator Affiliation:

UT MD Anderson Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

November 2009

Completion Date:

Related Keywords:

  • Blood Stem Cell Transplant Failure
  • Leukemia
  • Hematologic Malignancies
  • Hematologic Neoplasms
  • Blood Disorders
  • Blood Cancer
  • Transplantation, Blood And Marrow
  • Acute myelogenous leukemia
  • Myelodysplastic syndrome
  • Acute lymphocytic leukemia
  • Aplastic anemia
  • Chronic myelogenous leukemia
  • Chronic lymphocytic leukemia
  • Myeloproliferative disease
  • Hodgkin's disease
  • Non-Hodgkin's lymphoma
  • Multiple myeloma
  • Cyclophosphamide
  • Fludarabine
  • Melphalan
  • Mesna
  • Rituximab
  • Tacrolimus
  • Prograf
  • Mycofenolate mofetil
  • MMF
  • CellCept
  • Neoplasms
  • Leukemia
  • Hematologic Neoplasms



UT MD Anderson Cancer Center Houston, Texas  77030