Venetoclax Added to Fludarabine + Busulfan Prior to Transplant for AML, MDS, and MDS/MPN
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|ClinicalTrials.gov Identifier: NCT03613532|
Recruitment Status : Recruiting
First Posted : August 3, 2018
Last Update Posted : July 2, 2019
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 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.
- The name of the study drug involved in this study is Venetoclax.
- It is expected that about 38 people will take part in this research study.
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia (AML) Myelodysplastic Syndrome (MDS) Chronic Myelomonocytic Leukemia (CMML) MDS/Myeloproliferative Neoplasm-unclassifiable (MDS/MPN-unclassifiable) Hematopoietic Stem Cell Transplant||Drug: Venetoclax Drug: Fludarabine Drug: Busulfan||Phase 1|
- 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.
- In this research study, investigators are trying to determine a safe dose of the study drug, Venetoclax, when given in combination with a standard chemotherapy.
There are two phases in this research study:
- The first phase of the study is called the Dose-Escalation phase where venetoclax will be given in different doses until the safest maximum dose has been identified.
- The second phase of the study is call the Dose-Expansion phase where more participants will be treated at this dose level to obtain additional information on safety. 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. This chemotherapy is called the "conditioning regimen", which is treatment required to prepare the body for bone marrow transplantation). 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 that will be given as a part of the conditioning regimen.
- The FDA (U.S. Food and Drug Administration) has not approved Venetoclax for this specific disease, but it is approved for other uses. Venetoclax is an oral drug that selectively inhibits Bcl-2, which is critical for keeping cancer cells alive.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||38 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study of Venetoclax Added to Busulfan and Fludarabine Reduced Intensity Conditioning Regimen for AML, MDS, and MDS/MPN Overlap Syndromes|
|Actual Study Start Date :||October 1, 2018|
|Estimated Primary Completion Date :||October 1, 2020|
|Estimated Study Completion Date :||February 1, 2021|
This trial can be divided into three periods: 1) Screening, 2) Treatment including venetoclax + FluBu2 and transplantation; and 3) Post-Transplant follow up.
Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation.
6-7 total doses depending on dose level assigned
Other Name: ABT199
◦Fludarabine : given once daily for 4 days
Other Name: Fludara
◦Busulfan: given twice daily for 4 days
- MTD of Venetoclax with Busulfan and Fludarabine [ Time Frame: 37 Days ]Determine safe dose and schedule of venetoclax
- Overall Survival [ Time Frame: 12 Months ]Time from treatment start until death
- Progression Free Survival [ Time Frame: 12 Months ]Time from treatment start until relapse
- Overall Response Rate [ Time Frame: At day 100, 6 months and 12 months ]IWG response criteria
- Remission Duration Rate [ Time Frame: from start of the treatment until disease relapse (assessed at day 100, 6 months and 12 months) ]Duration of remission from treatment start until relapse
- Rate of Disease Relapse [ Time Frame: 12 Months ]Frequency of disease recurrence on trial
- Rate of Non-Relapse Mortality [ Time Frame: 12 Months ]Frequency of death that is not due to disease recurrence on trial
- Donor granulocyte chimerism percentage [ Time Frame: 28 Days Post-Transplant ]Percentage of donor blood cells
- Donor granulocyte chimerism percentage [ Time Frame: 100 days Post-Transplant ]Percentage of donor blood cells
- Donor granulocyte chimerism percentage [ Time Frame: 12 Months Post-Transplant ]Percentage of donor blood cells
- Cumulative incidence of acute graft versus host disease (GVHD) and chronic GVHD following allo-HCT [ Time Frame: 12 Months ]Frequency of GVHD events
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03613532
|Contact: Jacqueline S. Garcia, MD||617-632-1906||Jacqueline_garcia@dfci.harvard.edu|
|United States, Massachusetts|
|Dana-Farber Cancer Institute||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: Jacqueline S Garcia, MD 617-632-1906 firstname.lastname@example.org|
|Principal Investigator: Jacqueline S Garcia, MD|
|Principal Investigator:||Jacqueline S. Garcia, MD||Dana-Farber Cancer Institute|