Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Azacitidine

Cc-486

Antimetabolites

Enzyme Inhibitors

Patients on study will receive 300 mg CC-486 for 14 out of 28 days per cycle with dose modification according to the Onureg United States Prescribing Information (USPI). Up to 3 cycles of CC-486 will be allowed, and a minimum of 1 cycle is to be given prior to transplant. Multiple cycles will be allowed only if donor-specific or logistical issues prevent transplantation after the first cycle. CC-486 will be dispensed on day 1 of each treatment cycle and only 1 cycle equivalent is to be dispensed at the beginning of each cycle.

Post-transplant maintenance with CC-486 can be started 60 days (range 60-120 days) after hematopoietic progenitor cell infusion which should allow time for count and graft recovery after post-transplant cyclophosphamide (PTCY). The CC-486 maximum preferred pre-emptive dose post-ASCT is 200 mg daily, which will be administered for 14 of 28 days per cycle (max 12 cycles).

Oral azacitidine is indicated for continued treatment of adult patients with acute myeloid leukemia who achieved first complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy and are not able to complete intensive curative therapy.

oral azacitidine (CC-486)

Lohith Gowda, MD

Marcos de Lima, MD

To investigate the feasibility of delivering oral azacitidine (CC-486) as a consolidation regimen from the time of first complete remission (CR1), in patients with acute myelogenous leukemia (AML) eligible for curative intent Allogeneic Stem Cell Transplant (ASCT).

A significant proportion of patients with Acute myeloid leukemia (AML) who are fit to receive intensive chemotherapy and reach first complete remission (CR), relapse despite further high or low intensity therapies. Relapse/refractory (R/R) AML generally portends poor outcomes and available agents to treat this condition have modest efficacy. Until the recent approval of CC-486 as a maintenance therapy, no other drug had shown overall survival (OS) advantage for patients with AML in first complete remission (CR1). In the CC-486 registration trial (QUAZAR AML-01), remission induction was achieved by intensive chemotherapy, but patients were ineligible to proceed to allogeneic stem cell transplant (ASCT) at the time of screening. Post CR1, CC-486 apart from prolonging remission was also successful in deepening the quality of remission by eradicating measurable residual disease (MRD). It is therefore logical to investigate the feasibility of CC-486 as a consolidation regimen from the time of CR1, in patients eligible for curative intent ASCT. It is anticipated that continued epigenetic priming peri-ASCT with CC-486 can favorably alter disease biology for AML patients in CR1, modulate immune surveillance to decrease relapse risk, mitigate adverse graft versus host disease (GVHD) biology without significant compromise on the quality of life. This pilot study will assess the suitability of CC-486 as a bridge to transplant, will help optimize the timing between CC-486 administration and the start of transplant preparative regimen, and will assess the utility of continued CC-486 maintenance post-transplant.

Oral Azacitidine (CC-486) Epigenetic Priming and Maintenance for Adult Acute Myeloid Leukemia (AML) Patients

A Pilot Study of Oral Azacitidine (CC-486) Epigenetic Priming and Maintenance in Adult AML Patients Eligible for Reduced Intensity Allogeneic Stem Cell Transplant

To identify the number of participants able to receive a minimum of 1 and a maximum of 3 cycles of CC-486 consolidation therapy as a bridge to Reduced Intensity Conditioning (RIC) ASCT while maintaining first complete remission- CR1.

Adverse events (AEs) occurring in the participants will be graded according to NCI CTCAE v 5.0 with each cycle of CC_486 administered pre-transplant.

With CC-486 consolidation prior to transplant best response to treatment and disease status will be measured. Response criteria or loss of response (including frank morphologic relapse) will be assessed by using peripheral blood or bone marrow samples as per European Leukemia Net (ELN) AML 2017 guidelines.

Bone marrow biopsies will be performed longitudinally post-transplant. Prior to initiating first cycle of CC-486 maintenance post-transplant, disease status confirmation with a bone marrow biopsy in the prior 14 days would be needed. Response criteria or loss of response will be defined as per European Leukemia Net (ELN) AML 2017 guideline. Based on best response observed duration of remission, cumulative incidence of relapse, patterns of relapse will be described. Participants will be assessed at days 30, 60, 120, 180, 365 and 720 for disease relapse.

As assessed by the number of cycles administered and the periods of interruptions.

As assessed by the length of survival in months from the time of 1st cycle of CC-486 pretransplant, from the time of transplant and from the time of starting maintenance post-transplant.

As assessed by cumulative incidence of acute and chronic graft versus host disease (GVHD) within 2 years from the date of transplant.

As assessed by kinetics of chimerism changes for those receiving CC-486. Based on institutional practices peripheral blood and or bone marrow samples would be used for chimerism testing. Donor/recipient hematopoiesis fraction will be reported across cellular subset per institutional standards.

Quality of life questionnaire administered pre- and post-transplant with CC-486 maintenance use. The Likert scale from zero to four \[0-4\] is used to measure the responses for each question after taking into account reverse scores for questions constructed in a negative form. The final score for FACT-BMT ranges from zero to 196. Higher scores for the scales and subscales indicate better quality of life.

Adverse events (AEs) occurring in the participants will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 5.0 with each cycle of CC_486 administered post-transplant.

Spots Global Cancer Trial Database for reduced intensity allogeneic stem cell transplant