Overview

This trial is active, not recruiting.

Conditions blood stem cell transplant failure, leukemia, hematologic malignancies
Treatments cyclophosphamide, fludarabine, melphalan, mesna, rituximab, stem cell transplantation, thiotepa, tacrolimus, mycofenolate mofetil, g-csf
Phase phase 2
Target CD20
Sponsor M.D. Anderson Cancer Center
Start date November 2009
End date November 2016
Trial size 337 participants
Trial identifier NCT01010217, 2009-0266, NCI-2011-03144

Summary

The goal of this clinical research study is to learn about the safety of giving a stem cell transplant from a tissue-mismatched donor, followed by cyclophosphamide, to patients with certain types of blood disorders or blood cancers. Melphalan, thiotepa, and fludarabine will also be given before the transplant.

Researchers will study the health status of these patients at 3 months after the transplant.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Arm 1 - Stem Cell Transplantation (SCT), Melphalan 140 mg/m^2 , Thiotepa 5 mg/kg, Fludarabine 40 mg/m^2 + high-dose post-transplant cyclophosphamide 50 mg/kg/day
cyclophosphamide Cytoxan
50 mg/kg/day intravenous (IV) over 3 hours on Days 3 and 4.
fludarabine Fludara
40 mg/m^2 IV over 1 hour on Days -6, -5, -4, and -3.
melphalan Alkeran
140 mg/m^2 IV (or 100 mg/m^2 with reduced intensity Regimen 2) over 30 minutes on Day -8.
mesna Mesnex
10 mg/kg IV every 4 hours for a total of 10 doses starting just prior to first dose of Cyclophosphamide on Days 3 and 4.
rituximab Rituxan
CD20+ lymphoid malignancies: 375 mg/m2 on Day -13 followed by 1000 mg/m2 on Day -6, +1, and +8.
stem cell transplantation SCT
Infusion of donor's stem cells by vein on Day 0, may last anywhere from 15 minutes to several hours.
thiotepa
5 mg/kg Regimen 1 (or 5 mg/kg with reduced intensity Regimen 2) IV over 4 hours on Day -7.
tacrolimus Prograf
0.015 mg/kg by vein or orally daily starting on Day +5 for 3 months
mycofenolate mofetil MMF
15 mg/kg/dose orally three times a day starting on Day +5 to Day +100 or otherwise indicated
g-csf Filgrastim
5 mcg/kg/day subcutaneously starting Day 7 once a day daily until neutrophil recovery > 1000/mcl.
(Experimental)
Arm 2 - SCT, Melphalan, Thiotepa, Fludarabine + high-dose post-transplant cyclophosphamide.
cyclophosphamide Cytoxan
50 mg/kg/day intravenous (IV) over 3 hours on Days 3 and 4.
fludarabine Fludara
40 mg/m^2 IV over 1 hour on Days -6, -5, -4, and -3.
melphalan Alkeran
140 mg/m^2 IV (or 100 mg/m^2 with reduced intensity Regimen 2) over 30 minutes on Day -8.
mesna Mesnex
10 mg/kg IV every 4 hours for a total of 10 doses starting just prior to first dose of Cyclophosphamide on Days 3 and 4.
rituximab Rituxan
CD20+ lymphoid malignancies: 375 mg/m2 on Day -13 followed by 1000 mg/m2 on Day -6, +1, and +8.
stem cell transplantation SCT
Infusion of donor's stem cells by vein on Day 0, may last anywhere from 15 minutes to several hours.
thiotepa
5 mg/kg Regimen 1 (or 5 mg/kg with reduced intensity Regimen 2) IV over 4 hours on Day -7.
tacrolimus Prograf
0.015 mg/kg by vein or orally daily starting on Day +5 for 3 months
mycofenolate mofetil MMF
15 mg/kg/dose orally three times a day starting on Day +5 to Day +100 or otherwise indicated
g-csf Filgrastim
5 mcg/kg/day subcutaneously starting Day 7 once a day daily until neutrophil recovery > 1000/mcl.
(Experimental)
Arm 3 - SCT, Melphalan, Thiotepa, Fludarabine + high-dose post-transplant cyclophosphamide
cyclophosphamide Cytoxan
50 mg/kg/day intravenous (IV) over 3 hours on Days 3 and 4.
fludarabine Fludara
40 mg/m^2 IV over 1 hour on Days -6, -5, -4, and -3.
melphalan Alkeran
140 mg/m^2 IV (or 100 mg/m^2 with reduced intensity Regimen 2) over 30 minutes on Day -8.
mesna Mesnex
10 mg/kg IV every 4 hours for a total of 10 doses starting just prior to first dose of Cyclophosphamide on Days 3 and 4.
tacrolimus Prograf
0.015 mg/kg by vein or orally daily starting on Day +5 for 3 months
mycofenolate mofetil MMF
15 mg/kg/dose orally three times a day starting on Day +5 to Day +100 or otherwise indicated
g-csf Filgrastim
5 mcg/kg/day subcutaneously starting Day 7 once a day daily until neutrophil recovery > 1000/mcl.

Primary Outcomes

Measure
100-Day Non-relapse Mortality (NRM)
time frame: At 100 days

Eligibility Criteria

Male or female participants up to 75 years old.

Inclusion Criteria: 1. Patients < 55 years (Myeloablative regimen #1) or > 55 and 3 abnormalities], peripheral blood blasts <1000/microliter, AML patients must show response to most recent received chemotherapy; 4. AML in second or greater remission, primary induction failure and patients with relapsed disease, peripheral blood blasts <1000/microliter; patients > 55 years and /=1st chronic phase, after failed >/=2 lines of tyrosine kinase inhibitors; in accelerated or blast phase with > 30% bone marrow blasts; 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 #2 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. Patients above >/=65 years old should have an age-adjusted co-morbidity index of /=50 ml/min (calculated with Cockcroft-Gault formula); Creatinine for children /= 45% predicted corrected for hemoglobin. For pediatric patients, if unable to perform pulmonary function, >/= 92% oxygen saturation with pulse oximetry. 19. LVEF >/= 40%. 20. 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. Patients with AML must have less than 30% bone marrow blasts and no peripheral blood blasts. 6. 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-invasive 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.) 7. Positive Beta HCG test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization. 8. Inability to comply with medical therapy or follow-up.

Additional Information

Official title 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
Description 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 transplant. 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 transplant). - 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 will receive total body irradiation (TBI) on Day -1. 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 35. 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 performed: - You will have a physical exam. - Blood (about 4 tablespoons) will be drawn for routine tests. - You will have a bone marrow biopsy/aspirate to check the status of the disease. If you have lymphoma or aplastic anemia, you may have a bone marrow biopsy/aspirate at 3, 6, and 12 months, if your doctor thinks it is needed. - 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 337 patients will take part in this study. All will be enrolled at MD Anderson.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by M.D. Anderson Cancer Center.