This clinical trial involves individuals who have been diagnosed with Acute Myeloid Leukemia
(AML), Myelodysplastic Syndrome (MDS), Chronic Myelomonocytic Leukemia (CMML), or
MDS/myeloproliferative neoplasm-unclassifiable (MDS/MPN-unclassifiable) and are planning to
have an allogeneic hematopoietic stem cell transplant ("bone marrow transplant"). The goal of
this research study is to (1) test the safety of adding the study drug, Venetoclax, to a
standard of care conditioning regimen for bone marrow transplantation as a possible means of
eliminating residual (left-over) disease prior to transplant and (2) to test the safety of
combination Venetoclax and azacitidine as "maintenance therapy" after transplant to possibly
prevent disease recurrence.
The name of the study drug involved in this study is Venetoclax.
It is expected that about 42 people will take part in this research study.
This research study is a Phase I clinical trial, which tests the safety of an
investigational drug and tries to define the appropriate dose and schedule of the
investigational drug to use for further studies. "Investigational" means that the drug
is being studied.
There are two parts to this research study:
Part 1 is to determine a safe dose of the study drug, Venetoclax, when given in
combination with a standard chemotherapy and Part 2 is to determine the safety of
post-transplant maintenance therapy with the combination of azacytidine and
venetoclax. Participants enrolled in Part 1 of this study, will receive Venetoclax
in combination with conditioning chemotherapy (prior to transplantation).
Participants enrolled in Part 2 of the study, will also receive Venetoclax in
combination with conditioning chemotherapy (prior to transplantation) and will have
the opportunity to receive maintenance chemotherapy (after transplantation) for
potentially a year.
Both Part 1 and Part 2 of this research study will have a Dose-Escalation phase. The
Dose-Escalation phase is the part of the study where treatment dose and schedule are
In Part 1, the Dose-Escalation phase is when venetoclax will be given at different
doses until the safest maximum dose has been identified. Part 1 also includes a
second phase of the study which is called the Dose-Expansion phase, during which
more participants will be treated at this dose level to obtain additional
information on safety.
In Part 2, the Dose-Escalation phase is where the combination of venetoclax and
azacitidine will be given after transplantation at different schedules.
For both the Dose-Escalation or Dose-Expansion phase of this study, there will be a
screening period, a pre-transplant period, a transplant period, and a
post-transplant follow up period.
In this research study, participants will receive venetoclax plus chemotherapy.
Participants in Part 1 and Part 2 of this study will receive chemotherapy immediately
prior to transplantation, which is called the "conditioning regimen." The conditioning
regimen chemotherapy will suppress the immune system and may help to destroy cancer
cells. During this process normal bone marrow cells are destroyed as well, thus making
way for donor stem cells.
Fludarabine and busulfan (FluBu2) are both chemotherapies and a common conditioning
In this study, Venetoclax is added to the conditioning regimen (FluBu2) prior to
transplantation to eliminate leftover blood cancer cells prior to transplant.
Participants in Part 2 of the study will also have the opportunity to receive
venetoclax plus azacitidine after transplantation. The combination of these two
drugs is called "maintenance therapy," which is treatment given after transplant to
potentially reduce the chance of disease relapse. Relapse is a cause of transplant
failure and can occur when there are leftover blood cancer cells.
The FDA (U.S. Food and Drug Administration) has approved Venetoclax in combination with
cytarabine, azacitidine or decitabine for the treatment of newly diagnosed acute myeloid
leukemia, but not for use in with conditioning chemotherapy prior to transplantation or
after transplant with maintenance chemotherapy. Venetoclax is an oral drug that
selectively inhibits Bcl-2, which is critical for keeping cancer cells alive.
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.
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