Mismatched Transplantation Using High-dose Post-transplant Cyclophosphamide
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
2 other identifiers
interventional
176
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Nov 2009
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 5, 2009
CompletedFirst Submitted
Initial submission to the registry
November 6, 2009
CompletedFirst Posted
Study publicly available on registry
November 9, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 5, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
October 5, 2017
CompletedResults Posted
Study results publicly available
January 7, 2020
CompletedMarch 25, 2020
March 1, 2020
7.9 years
November 6, 2009
May 15, 2019
March 12, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants With Non-relapse Mortality (NRM)
Non-relapse mortality (NRM) is defined as death from any cause other than relapse disease. Bayesian monitoring scheme described in Thall, Simon, and Estey (1996) employed to perform interim monitoring of the data during the course of the trial separately within each group.
At 100 days
Secondary Outcomes (5)
Number of Participants With Non Related Mortality (NRM)
six months
Engraftments
Day 28
Grade III-IV aGVHD
100 days
cGVHD
1 year
Disease Free Survival
1 year
Study Arms (3)
Haploidentical related
EXPERIMENTALArm 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
1 Antigen Mismatch Related or Unrelated
EXPERIMENTALArm 2 - SCT, Melphalan, Thiotepa, Fludarabine + high-dose post-transplant cyclophosphamide.
Matched Unrelated Donor (MUD)
EXPERIMENTALArm 3 - SCT, Melphalan, Thiotepa, Fludarabine + high-dose post-transplant cyclophosphamide
Interventions
50 mg/kg/day intravenous (IV) over 3 hours on Days 3 and 4.
40 mg/m\^2 IV over 1 hour on Days -6, -5, -4, and -3.
140 mg/m\^2 IV (or 100 mg/m\^2 with reduced intensity Regimen 2) over 30 minutes on Day -8.
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.
CD20+ lymphoid malignancies: 375 mg/m2 on Day -13 followed by 1000 mg/m2 on Day -6, +1, and +8.
Infusion of donor's stem cells by vein on Day 0, may last anywhere from 15 minutes to several hours.
5 mg/kg Regimen 1 (or 5 mg/kg with reduced intensity Regimen 2) IV over 4 hours on Day -7.
0.015 mg/kg by vein or orally daily starting on Day +5 for 3 months
15 mg/kg/dose orally three times a day starting on Day +5 to Day +100 or otherwise indicated
5 mcg/kg/day subcutaneously starting Day 7 once a day daily until neutrophil recovery \> 1000/mcl.
Eligibility Criteria
You may qualify if:
- 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:
- 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;
- 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;
- AML in second or greater remission, primary induction failure and patients with relapsed disease, peripheral blood blasts \<1000/microliter; patients \> 55 years and \</= 75 years need to be in morphologic remission at transplant (\< 5% blasts).
- Myelodysplastic syndrome (MDS) with International Prognostic Scoring System (IPSS) intermediate-2 or higher; or therapy-related MDS
- Aplastic anemia with Absolute neutrophil count (ANC)\<1000 and transfusion dependent after they failed immunosuppression therapy
- 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;
- Prior allogeneic stem cell transplant more than 6 months from the first transplant, in remission.
- Chemotherapy-sensitive relapsed lymphoma (Complete or partial response), Hodgkin's or non-Hodgkin's lymphoma, no evidence of "bulky" disease (\> 10 cm in diameter);
- Patients with chemo-sensitive CLL with persistent or recurrent disease after fludarabine-based regimens, no evidence of "bulky" disease (\> 10 cm in diameter)
- 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.
- Patients with myelofibrosis (Lille \>0, transfusion dependency, progression to blast phase; however, in remission from AML) or chronic myelomonocytic leukemia (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.
- Zubrod performance status 0-1 or Lansky PS greater or equal to 70%.
- Patients above \>/=65 years old should have an age-adjusted co-morbidity index of \</= 3.
- 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.
- +5 more criteria
You may not qualify if:
- HIV positive; active hepatitis B or C
- Patients with active infections. The PI is the final arbiter of the eligibility.
- Liver cirrhosis with greater than grade 1 stage 1 inflammation/fibrosis
- Uncontrolled central nervous system (CNS) involvement by tumor cells
- Patients with AML must have less than 30% bone marrow blasts and no peripheral blood blasts.
- 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.)
- Positive Beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.
- Inability to comply with medical therapy or follow-up.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Stefan O Ciurea, Associate Profeddor of Stem Cell Transplantation
- Organization
- UT MD Anderson Cancer Center
Study Officials
- STUDY CHAIR
Stefan Ciurea, MD
M.D. Anderson Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 6, 2009
First Posted
November 9, 2009
Study Start
November 5, 2009
Primary Completion
October 5, 2017
Study Completion
October 5, 2017
Last Updated
March 25, 2020
Results First Posted
January 7, 2020
Record last verified: 2020-03