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Mismatched Transplantation Using High-dose Post-transplant Cyclophosphamide

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01010217
First received: November 6, 2009
Last updated: May 29, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Blood Stem Cell Transplant Failure
Leukemia
Hematologic Malignancies
Drug: Cyclophosphamide
Drug: Fludarabine
Drug: Melphalan
Drug: Mesna
Drug: Rituximab
Procedure: Stem Cell Transplantation
Drug: Thiotepa
Drug: Tacrolimus
Drug: Mycofenolate mofetil
Drug: G-CSF
Phase 2

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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Non-relapse Mortality (NRM) [ Time Frame: At 100 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 237
Study Start Date: November 2009
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Haploidentical related
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
Drug: Cyclophosphamide
50 mg/kg/day intravenous (IV) over 3 hours on Days 3 and 4.
Other Names:
  • Cytoxan
  • Nesosar
Drug: Fludarabine
40 mg/m^2 IV over 1 hour on Days -6, -5, -4, and -3.
Other Names:
  • Fludara
  • Fludarabine Phosphate
Drug: Melphalan
140 mg/m^2 IV (or 100 mg/m^2 with reduced intensity Regimen 2) over 30 minutes on Day -8.
Other Name: Alkeran
Drug: Mesna
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.
Other Name: Mesnex
Drug: Rituximab
CD20+ lymphoid malignancies: 375 mg/m2 on Day -13 followed by 1000 mg/m2 on Day -6, +1, and +8.
Other Name: Rituxan
Procedure: Stem Cell Transplantation
Infusion of donor's stem cells by vein on Day 0, may last anywhere from 15 minutes to several hours.
Other Names:
  • SCT
  • Blood Marrow Transplantation
  • Allogeneic stem cell transplantation
  • ASCT
Drug: Thiotepa
5 mg/kg Regimen 1 (or 5 mg/kg with reduced intensity Regimen 2) IV over 4 hours on Day -7.
Drug: Tacrolimus
0.015 mg/kg by vein or orally daily starting on Day +5 for 3 months
Other Name: Prograf
Drug: Mycofenolate mofetil
15 mg/kg/dose orally three times a day starting on Day +5 to Day +100 or otherwise indicated
Other Names:
  • MMF
  • CellCept
Drug: G-CSF
5 mcg/kg/day subcutaneously starting Day 7 once a day daily until neutrophil recovery > 1000/mcl.
Other Names:
  • Filgrastim
  • Neupogen
Experimental: 1 Antigen Mismatch Related or Unrelated
Arm 2 - SCT, Melphalan, Thiotepa, Fludarabine + high-dose post-transplant cyclophosphamide.
Drug: Cyclophosphamide
50 mg/kg/day intravenous (IV) over 3 hours on Days 3 and 4.
Other Names:
  • Cytoxan
  • Nesosar
Drug: Fludarabine
40 mg/m^2 IV over 1 hour on Days -6, -5, -4, and -3.
Other Names:
  • Fludara
  • Fludarabine Phosphate
Drug: Melphalan
140 mg/m^2 IV (or 100 mg/m^2 with reduced intensity Regimen 2) over 30 minutes on Day -8.
Other Name: Alkeran
Drug: Mesna
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.
Other Name: Mesnex
Drug: Rituximab
CD20+ lymphoid malignancies: 375 mg/m2 on Day -13 followed by 1000 mg/m2 on Day -6, +1, and +8.
Other Name: Rituxan
Procedure: Stem Cell Transplantation
Infusion of donor's stem cells by vein on Day 0, may last anywhere from 15 minutes to several hours.
Other Names:
  • SCT
  • Blood Marrow Transplantation
  • Allogeneic stem cell transplantation
  • ASCT
Drug: Thiotepa
5 mg/kg Regimen 1 (or 5 mg/kg with reduced intensity Regimen 2) IV over 4 hours on Day -7.
Drug: Tacrolimus
0.015 mg/kg by vein or orally daily starting on Day +5 for 3 months
Other Name: Prograf
Drug: Mycofenolate mofetil
15 mg/kg/dose orally three times a day starting on Day +5 to Day +100 or otherwise indicated
Other Names:
  • MMF
  • CellCept
Drug: G-CSF
5 mcg/kg/day subcutaneously starting Day 7 once a day daily until neutrophil recovery > 1000/mcl.
Other Names:
  • Filgrastim
  • Neupogen
Experimental: Matched Unrelated Donor (MUD)
Arm 3 - SCT, Melphalan, Thiotepa, Fludarabine + high-dose post-transplant cyclophosphamide
Drug: Cyclophosphamide
50 mg/kg/day intravenous (IV) over 3 hours on Days 3 and 4.
Other Names:
  • Cytoxan
  • Nesosar
Drug: Fludarabine
40 mg/m^2 IV over 1 hour on Days -6, -5, -4, and -3.
Other Names:
  • Fludara
  • Fludarabine Phosphate
Drug: Melphalan
140 mg/m^2 IV (or 100 mg/m^2 with reduced intensity Regimen 2) over 30 minutes on Day -8.
Other Name: Alkeran
Drug: Mesna
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.
Other Name: Mesnex
Drug: Tacrolimus
0.015 mg/kg by vein or orally daily starting on Day +5 for 3 months
Other Name: Prograf
Drug: Mycofenolate mofetil
15 mg/kg/dose orally three times a day starting on Day +5 to Day +100 or otherwise indicated
Other Names:
  • MMF
  • CellCept
Drug: G-CSF
5 mcg/kg/day subcutaneously starting Day 7 once a day daily until neutrophil recovery > 1000/mcl.
Other Names:
  • Filgrastim
  • Neupogen

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients < 55 years (Myeloablative regimen #1) or > 55 and </= 75 years or significant comorbidities (Reduced intensity regimen #2) old lacking a matched related volunteer donor identified in time for transplant for which a related haploidentical donor (</= 7/8 allele match at the A, B, C, DR loci), a 7/8 allele matched related or unrelated donor is identified, or a matched unrelated donor (MUD). The patients must be diagnosed with a high-risk disease defined as following:
  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 chemotherapy;
  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 chemotherapy;
  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 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. 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 </= 1.5 mg/dl (unless Gilbert's syndrome), ALT or AST </= 200 IU/ml.
  16. Serum creatinine clearance >/=50 ml/min (calculated with Cockcroft-Gault formula); Creatinine for children </=1.5 mg/dl or </=2 times upper limit of normal for age (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. 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: 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01010217

Contacts
Contact: Stefan Ciurea, MD 713-794-5780

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Stefan Ciurea, MD         
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Study Chair: Stefan Ciurea, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01010217     History of Changes
Other Study ID Numbers: 2009-0266, NCI-2011-03144
Study First Received: November 6, 2009
Last Updated: May 29, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
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
G-CSF
Filgrastim
Neupogen

Additional relevant MeSH terms:
Leukemia
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Melphalan
Mycophenolate mofetil
Mycophenolic Acid
Rituximab
Tacrolimus
Thiotepa
Alkylating Agents
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014