A Phase II Study of Venetoclax in Combination With Azacitidine in the Post-Transplant Setting for AML, T Cell Leukemia, and Mixed Phenotype Acute Leukemia

Who is this study for? Adult patients with Acute Myeloid Leukemia
Status: Recruiting
Location: See location...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

This phase II trial studies how well venetoclax and azacitidine work for the treatment of acute myeloid leukemia after stem cell transplantation. Venetoclax may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Chemotherapy drugs, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax and azacitidine after a stem cell transplant may help control high risk leukemia and prevent it from coming back after the transplant.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 75
Healthy Volunteers: f
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• Participants 18 to 75 years of age.

• English and non-English speaking patients are eligible.

• Disease diagnosis with one of the hematological malignancies listed below and who are in morphological remission after allogeneic stem cell transplantation with PBSCs or bone marrow.

∙ AML if they had at least one of the following disease characteristics:

⁃ Therapy related AML.

• Cytogenetics and molecular features consistent with adverse risk group by European LeukemiaNet classification for AML (see Appendix A.).

• Primary induction failure defined as absence of complete remission after two different lines of anti-leukemia therapy following diagnosis.

• Presence of minimal residual disease by multi-color flow cytometry or cytogenetics or molecular studies at the time of HSCT.

• Presence of active disease defined as bone marrow blast count \>5% at the time of HSCT.

• Participants transplanted beyond first remission. OR

‣ Biphenotypic or bilineage leukemia (including a myeloid component) OR mixed phenotype acute leukemia (MPAL) OR

‣ Participants with acute lymphoblastic leukemia; B cell or T cell in original.

• Participants in morphological remission with no detectable minimal residual disase (MRD) after transplant

• Participants who are in remission with no detectable minimal residual disease (MRD) after allogeneic stem cell transplant should have:

∙ Adequate engraftment within 14 days prior to starting study drug:

‣ Absolute neutrophil count (ANC) \>/= 1.0 x 109/L without daily use of myeloid growth factor (G-CSF) for at least 7 days; and,

‣ Platelet \>/= 30 x 109/L without platelet transfusion within 1 week

‣ Be able to start the drug therapy between 42 to 100 days following HSCT.

• Use of one of the conditioning regimens as part of allogeneic stem cell transplant listed below:

∙ Reduced intensity regimen with fludarabine/melphalan (100-140 mg/m2) with or without TBI with post-transplant Cytoxan OR

‣ Myeloablative regimens including:

⁃ Busulfan (AUC at or greater than 4000)/fludarabine with post-transplant Cytoxan or total body irradiation (TBI)/etoposide with any graft versus host disease (GVHD) regimen OR

• Total body irradiation (TBI)/etoposide with any graft versus host disease (GVHD) regimen.

• Participants on clinical trials investigating different conditioning regimens (with the above described backbone) with investigational agents will be allowed to enroll.

• ECOG performance status of 0, 1, or 2.

• Serum creatinine \</=1.5 mg/dL or creatinine clearance greater or equal than 40 cc/min as defined by the Cockcroft-Gault Equation\*

⁃ Serum bilirubin \</= 1.5 x upper limit of normal (ULN).

⁃ Aspartate transaminase (AST) or alanine transaminase (ALT) \</= 2.5 x ULN.

⁃ Alkaline phosphatase \</= 2.5 x UL.

⁃ Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent.

⁃ Negative serum or urine pregnancy test for women with reproductive potential. The only subjects who will be exempt from this criterion are postmenopausal women (defined as women who have been amenorrheic for \> 12 months) or subjects who have been surgically sterilized or otherwise proven sterile. 3.1.2. For cohort #3 and cohort #4 patients (MRD positive cohort):

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• Participants 18 to 75 years of age.

• English and non-English speaking patients are eligible.

• Disease diagnosis with one of the hematological malignancies listed below and who are in morphological remission after allogeneic stem cell transplantation with PBSCs or bone marrow. a. AML OR b. Biphenotypic or bilineage leukemia (including a myeloid component) or mixed phenotype acute leukemia (MPAL) OR c. Participants with acute lymphoblastic leukemia; B cell or T cell in original.

• Persistence or reappearance of MRD by flow cytometry or cytogenetic or molecular testing while being in morphological remission after allogeneic stem cell transplantation.

∙ When MRD is detected by flow cytometry, disease level at or above the sensitivity level of the test will be required. • MRD level at or above 0.01% for B cell ALL and T cell ALL.

∙ • MRD level at or above 0.1% for AML and mixed phenotype acute leukemia.

‣ When MRD is detected by cytogenetics, disease level at or above the sensitivity level of the test will be required.

∙ • The limited of detection is about 0.25% for males and 0.44% for females.

‣ When MRD is detected by molecular testing, disease level at or above the sensitivity level of the test will be required. • The limited of detection is 0.01%

• Use of one of the conditioning regimens as part of allogeneic stem cell transplant listed below:

• a. Reduced intensity regimen with fludarabine/melphalan (100-140 mg/m2) with or without TBI with post-transplant Cytoxan OR b. Myeloablative regimens including:

• • Busulfan (AUC at or greater than 4000)/fludarabine with post-transplant Cytoxan or total body irradiation (TBI)/etoposide with any graft versus host disease (GVHD) regimen OR

⁃ Total body irradiation (TBI)/etoposide with any graft versus host disease (GVHD) regimen.

• Participants on clinical trials investigating different conditioning regimens (with the above described backbone) with investigational agents will be allowed to enroll.

• ECOG performance status of 0, 1, or 2.

• Serum creatinine \</=1.5 mg/dL or creatinine clearance greater or equal than 40 cc/min as defined by the Cockcroft-Gault Equation\*

• Serum bilirubin \</= 1.5 x upper limit of normal (ULN).

⁃ Aspartate transaminase (AST) or alanine transaminase (ALT) \</= 2.5 x ULN.

⁃ Alkaline phosphatase \</= 2.5 x UL.

⁃ Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent.

⁃ Negative serum or urine pregnancy test for women with reproductive potential. The only participants who will be exempt from this criterion are postmenopausal women (defined as women who have been amenorrheic for \> 12 months) or subjects who have been surgically sterilized or otherwise proven sterile.

Locations
United States
Texas
M D Anderson Cancer Center
RECRUITING
Houston
Contact Information
Primary
Betul Oran
boran@mdanderson.org
713-792-8750
Time Frame
Start Date: 2020-05-05
Estimated Completion Date: 2026-12-31
Participants
Target number of participants: 125
Treatments
Experimental: Treatment (azacitidine, venetoclax)
Patients receiving venetoclax and azacitidine for maintenance after allogeneic stem cell transplantation, receive azacitidine SC on days 1-5 and venetoclax PO QD on days 1-7. Patients receiving venetoclax and azacitidine for minimal residual disease after allogeneic stem cell transplant, receive azacitidine SC on days 1-5 and venetoclax PO QD on days 1-14. Treatment repeats every 4-8 weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Sponsors
Leads: M.D. Anderson Cancer Center

This content was sourced from clinicaltrials.gov

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