Comparing Cyclophosphamide and Abatacept With Standard of Care Treatment Following Stem Cell Transplantation in Patients With Hematologic Malignancy
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03680092|
Recruitment Status : Not yet recruiting
First Posted : September 21, 2018
Last Update Posted : September 26, 2019
|Condition or disease||Intervention/treatment||Phase|
|GVHD Hematologic Neoplasms||Drug: Cyclophosphamide Drug: abatacept Drug: Methotrexate Drug: Tacrolimus||Phase 2|
The experimental GVHD prophylaxis arm consists of cyclophosphamide and abatacept. Cyclophosphamide induces apoptosis of activated T cells and abatacept (CTLA4Ig) blocks activation of T cells by inhibiting the co-stimulatory signal.
Compared to the standard-of-care control arm, the experimental arm is much more convenient and expected to be associated with fewer toxicities.
In addition there is a great theoretical potential for immunological synergy between cyclophosphamide and abatacept for inducing post-transplant immunologic tolerance that clinically might translate into less GVHD without increase in relapse Patients will be randomized 1:1 to the experimental vs the standard of care arm. Randomization will be done prior to the use of any conditional therapy.
The two arms will be stratified by disease (acute leukemia vs others) and donor type (MRD vs MUD/MUD vs Haplo) in an effort to keep them balanced.
The conditioning regimen for both arms will be mainly Busulfan/Fludarabine (A Total Body Irradiation based conditioning regimen will be allowed for diseases such as ALL)
The GVHD prophylaxis regimen on the experimental arm will consist of high dose Cyclophosphamide on Days +3 and +4 followed by abatacept for 6 months.
The GVHD prophylaxis regimen on the standard of care arm will consist of methotrexate on Days +1,+3, +6 and +11 and tacrolimus for patients with a 10/10 matched related or unrelated donor and of high dose cyclophosphamide on Days +3 and +4 followed by tacrolimus and mycophenolate for patients with a haploidentical donor.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized Phase II Trial Comparing a Calcineurin Inhibitor-free Graft-versus-host Disease Prophylaxis Regimen With Post-transplantation Cyclophosphamide and Abatacept to Standard of Care|
|Estimated Study Start Date :||November 2019|
|Estimated Primary Completion Date :||August 2020|
|Estimated Study Completion Date :||August 2021|
Experimental: Cyclophosphamide and abatacept
The GVHD prophylaxis regimen on the experimental arm will consist of high dose Cyclophosphamide on Days +3 and +4 followed by abatacept for 6 months. Abatacept at a dose of 10mg/kg will be administered on days +5, +14 and +28, +56, +84, +112, +140, +168
Day 3 and day 4 following transplant. Dosing will be based on patients' actual weight up to 120% of ideal body weight, above which it will be based on adjusted ideal body weight (ideal weight plus 50% of the difference between ideal and actual weight).
Abatacept at a dose of 10mg/kg will be administered on days +5, +14 and +28, +56, +84, +112, +140, +168
Other Name: ORENCIA
Active Comparator: methotrexate and tacrolimus
The GVHD prophylaxis regimen on the standard of care arm will consist of methotrexate on Days +1,+3, +6 and +11 and tacrolimus
standard of care Methotrexate 5 mg/m2 on Days 1, 3, 6 and 11
Other Name: Trexall
Tacrolimus per institutional guidelines
- occurrence of moderate and severe chronic GVHD at one year post transplant [ Time Frame: through study completion, an average of 1 year ]The occurrence of moderate and severe chronic GVHD at one year post Chronic GVHD will be diagnosed and staged according to the previously published and widely accepted National Institutes of Health consensus criteria
- GVHD- and relapse- free survival by one year post transplant [ Time Frame: through study completion, an average of 1 year ]GVHD- and relapse- free survival will be defined as the absence of acute GVHD Grade III or IV or moderate or severe chronic GVHD or relapse or non-relapse mortality by one year post transplant. Acute GVHD will be diagnosed and graded according to Glucksberg criteria
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03680092
|Contact: Dimitrios Tzachanis, MD PhDemail@example.com|
|Contact: Elaine Engfirstname.lastname@example.org|
|United States, California|
|UC San Diego Moores Cancer Center|
|La Jolla, California, United States, 92093|
|Principal Investigator:||Dimitrios Tzachanis, MD PhD||University of California, San Diego|
|Principal Investigator:||Divya Koura, MD||University of California, San Diego|