Stem cell or bone marrow transplants can cure or control blood cancers. Sometimes the donor
cells see the recipient s body as foreign. This can cause complications. A high dose of the
drug cyclophosphamide (PTCy) can help reduce these risks. Researchers want to see if a lower
dose of PTCy can have the same benefits.
To see if a lower dose of PTCy will help people with blood cancers have a more successful
transplant and fewer side effects.
People ages 12-65 with leukemia, lymphoma, or multiple myeloma that is not curable with
standard therapy and is at high risk of returning without transplant, and their healthy adult
Transplant participants will be screened with:
Blood, urine, breathing, and heart tests
Bone marrow samples: A needle inserted into the participant s pelvis will remove marrow and a
Transplant recipients will stay at the hospital and be prepped with chemotherapy over 6 days
for the transplant. They will get stem cells through a catheter in the chest or neck. They
will get the cyclophosphamide chemotherapy. They will stay in the hospital about 4 more
weeks. They will have blood transfusions. They will have frequent blood tests and 2 bone
marrow samples within 1 year after the transplant.
Donor participants will be screened with:
Blood, urine, and heart tests
Donor participants will have bone marrow taken from their pelvis or stem cells taken from
their blood. For the blood donation, blood will be taken from a vein in one arm, move through
a machine to remove white blood cells, and be returned through a vein in the other arm.
Participation will last up to 5 years....
Post-transplantation cyclophosphamide (PTCy) reduces rates of severe acute and chronic
graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation
(HCT) and safely facilitates human leukocyte antigen (HLA)-haploidentical HCT
When clinically translated, the dose (50 mg/kg) and timing (days +3 and +4) of PTCy used
were partly extrapolated from murine major histocompatibility complex (MHC)-matched skin
allografting models and were partly empirical
In both MHC-haploidentical and MHC-disparate murine HCT models, a dose of 25 mg/kg/day
was superior to 50 mg/kg/day on days +3 and +4 in terms of GVHD severity and mortality
In the MHC-haploidentical HCT model, a dose of 25 mg/kg on day +4 was equivalent to 25
mg/kg/day on days +3 and +4
In addition to better GVHD prevention, lower dosing of PTCy is associated with less
broad reduction of T-cell numbers after PTCy
-Determine whether a dose of PTCy 25 mg/kg on day +3 and +4 or on day +4 only can maintain
adequate protection against grade III-IV acute GVHD.
Histologically or cytologically confirmed hematologic malignancy with standard
indication for allogeneic hematopoietic cell transplantation including one of the
Acute myeloid leukemia (AML) of intermediate or adverse risk disease by the 2017
European LeukemiaNet criteria in first morphologic complete remission
AML of any risk in second or subsequent morphologic complete remission
B-cell acute lymphoblastic leukemia in first or subsequent complete remission
T-cell acute lymphoblastic leukemia with minimal residual disease detected after
first line therapy and/or adverse genetics
Myelodysplastic syndrome of intermediate or higher score by the Revised
International Prognostic Scoring System (IPSS-R)
Primary myelofibrosis of intermediate-2 or higher risk by the Dynamic International
Prognostic Scoring System (DIPSS)
Chronic myelomonocytic leukemia
Chronic myelogenous leukemia resistant to or intolerant of greater than or equal to
3 tyrosine kinase inhibitors or with prior history of accelerated phase or blast
B-cell lymphoma including Hodgkin lymphoma that has relapsed within 1 year of
completion of primary treatment
Chronic lymphocytic leukemia with 17p deletion and/or unmutated IgHV or refractory
to or intolerant of both BTK and PI3K inhibitors
Mature T or NK neoplasms as defined in the WHO guidelines of sufficient type and
severity for allogeneic HCT based on the Prognostic Index for T- cell lymphoma
(PIT) score of low-intermediate risk or higher or on recently published clinical
Hematologic malignancy of dendritic cell or histiocytic cell type
Multiple myeloma, stage III, relapsing after therapy with both a proteasome
inhibitor and an immunomodulatory drug (IMiD)
At least one potentially suitable HLA-haploidentical donor.
Karnofsky performance score greater than or equal to 60
Adequate organ function
Open-label, single-center, non-randomized, phase I/II study
All patients will receive myeloablative conditioning, HLA-haploidentical bone marrow
HCT, and GVHD prophylaxis with PTCy, MMF, and sirolimus.
A small pilot of 5 evaluable patients will receive the standard PTCy 50 mg/kg on days
+3/+4 to obtain a limited amount of comparative pharmacokinetic and T-cell
immunophenotyping and repertoire data
Then the study will proceed to a small, two-level [1) 25 mg/kg/day on days +3 and +4, 2)
25 mg/kg on day +4 only] phase I dose de-escalation study based on the standard 3+3
Patients will be evaluated for development of grade III-IV acute GVHD (aGVHD) at day +60
as the dose-limiting toxicity and then phase II will proceed with the shorter duration
of the days of treatment (+3/+4 or +4) which is associated with 0-1 of 6 patients with
grade III- IV aGVHD at day +60 and with the least amount of toxicity
Simon optimal two-stage phase II trial design, to rule out excess grade III-IV acute
GVHD with this decreased PTCy exposure, will be used in the phase II portion of the
study which will enroll an additional 14 patients to see if this lower PTCy exposure is
associated with a similar rate of grade III-IV acute GVHD as is expected with 50 mg/kg
on days +3/+4
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.