Comparing Cyclophosphamide and Abatacept With Standard of Care Treatment Following Stem Cell Transplantation in Patients With Hematologic Malignancy
| Status: | Not yet recruiting |
|---|---|
| Conditions: | Blood Cancer, Hematology |
| Therapuetic Areas: | Hematology, Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/5/2019 |
| Start Date: | August 2019 |
| End Date: | August 2021 |
| Contact: | Dimitrios Tzachanis, MD PhD |
| Email: | dtzachanis@ucsd.edu |
| Phone: | 858-534-2185 |
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
The purpose of this study is to investigate whether the combination of cyclophosphamide and
abatacept versus the treatment used in standard of care will reduce the incidence of moderate
and severe chronic graft-versus-host disease (GVHD) following hematopoietic stem cell
transplantation. GVHD occurs when the cells from your donor (the graft) see your body's cells
(the host) as different and attack them.
abatacept versus the treatment used in standard of care will reduce the incidence of moderate
and severe chronic graft-versus-host disease (GVHD) following hematopoietic stem cell
transplantation. GVHD occurs when the cells from your donor (the graft) see your body's cells
(the host) as different and attack them.
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.
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.
Inclusion Criteria:
- High risk hematologic malignancy justifying the need for an allogeneic hematopoetic
stem cell transplantation: AML, ALL, CML in accelerated or blast phase, MDS/MPN, NHL,
Hodgkin lymphoma, and multiple myeloma
- Creatinine clearance > 40
- Adequate hepatic function
- Normal cardiac function (EF > 50%)
Exclusion Criteria:
- Patients with hematologic malignancies for which transplant is not the only curative
option, such as AML with good or intermediate cytogenetics or molecular markers in CR1
or CML in chronic phase
- Inability to identify an 10/10 HLA-Matched Donor (related or unrelated) or a
haploidentical donor
- Active malignant disease relapse
- Active, uncontrolled infection, uncontrolled cardiac angina, symptomatic congestive
heart failure
- Life expectancy <3 months
- Pregnancy or lactation
- Patients may not be receiving any other investigational agents in the last 28 days
- Patients with chronic myeloid leukemia in first chronic phase
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