Guadecitabine + Donor Lymphocytes for Leukemia Relapse After Transplant

Recruiting in Palo Alto (17 mi)

Overseen ByBetul Oran

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: M.D. Anderson Cancer Center

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?This trial studies how well guadecitabine works in patients with AML or MDS who relapsed after a stem cell transplant. Guadecitabine is a new type of treatment similar to other drugs that have been effective in treating these conditions. The treatment involves injections of guadecitabine and possibly additional help from donor cells. The drug aims to stop cancer growth and prevent harmful immune reactions, while the donor cells help the immune system fight cancer.

Eligibility Criteria

This trial is for patients with acute myeloid leukemia or myelodysplastic syndrome that's come back after a stem cell transplant. Participants must have a good match with their donor, be in specific stages of disease recovery or relapse, and have stable organ function without severe infections or active graft versus host disease. They can't join if they've had certain heart issues recently, uncontrolled infections, multiple transplants, or are HIV positive.

Inclusion Criteria

My donor and I have a maximum of one mismatch in our HLA markers.

Be able to start the drug therapy between 42 to 100 days following allogeneic SCT; No more than 1 prior allogeneic SCT; Post-transplant bone marrow consistent with complete remission with no evidence of minimal residual disease by flow-cytometry or cytogenetics or molecular testing; Adequate engraftment within 14 days prior to starting study drug: absolute neutrophil count (ANC) >= 1.0 x 10^9/L without daily use of myeloid growth factor; and, platelet >= 50 x 10^9/L without platelet transfusion within 1 week; Eastern Cooperative Oncology Group (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 upper limit (UL); No active bleeding; No uncontrolled graft versus host disease (GVHD); No clinical evidence of life-threatening infection; Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent; Human immunodeficiency virus (HIV) negative and hepatitis B surface antigen (HBs-Ag) negative; 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

My cancer has returned or is still present after a stem cell transplant, even though it looks like I'm in remission.

+6 more

Exclusion Criteria

Use of any anti-leukemic agents after relapse is documented (note that the use of these anti-leukemic agents given as post-transplant maintenance therapy is allowed in this study, e.g., subcutaneous or oral 5-azacytidine or FLT3 inhibitors for maintenance) for cohorts 1 and 2; Bone marrow blast count > 60% for cohort 1; Use of any of the following after transplantation and prior to starting study therapy for cohort 3: Investigational agents/therapies; Anti-leukemic agents given as post-transplant maintenance therapy (e.g., subcutaneous or oral 5-azacytidine or FLT3 inhibitors for maintenance); Active acute graft versus host disease (GVHD) grade II or higher; Active chronic GVHD that is extensive; Concurrent use of systemic immune suppressive other than calcineurin inhibitors and sirolimus; Active uncontrolled systemic fungal, bacterial or viral infection; Symptomatic or uncontrolled arrhythmias; Significant active cardiac disease within the previous 6 months, including: New York Heart Association (NYHA) class III or IV congestive heart failure; unstable angina or angina requiring surgical or medical intervention, and/or; myocardial infarction; Known active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); Prior history of solid tumor unless the subject has been free of the disease for >= 1 year; however, subjects with the following history/concurrent conditions are allowed: basal or squamous cell carcinoma of the skin; carcinoma in situ of the cervix; carcinoma in situ of the breast; incidental histologic finding of prostate cancer (T1a or T1b using the tumor, node, metastasis [TNM] clinical staging system)

Participant Groups

The study tests guadecitabine's effectiveness in treating cancer recurrence post-transplant. It examines whether the drug can prevent growth of cancer cells and enhance the immune response against them when followed by an infusion of donor white blood cells (donor lymphocyte infusion).

1Treatment groups

Experimental Treatment

Group I: Treatment (guadecitabine, DLI)Experimental Treatment3 Interventions

Patients receive guadecitabine SC QD on days 1-5. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive DLI IV over 10-30 minutes on day 6 of cycles 2, 4, and 6 in the absence of disease progression or unacceptable toxicity.