This phase II trial studies how well clofarabine and melphalan before a donor stem cell
transplant works in treating patients with a decrease in or disappearance of signs and
symptoms of myelodysplasia or acute leukemia. Giving chemotherapy, such as clofarabine and
melphalan, before a donor stem cell transplant helps stop the growth of cancer cells. It may
also stop the patient's immune system from rejecting the donor's stem cells. When the
healthy stem cells from a donor are infused into a patient they may help the patient's bone
marrow make stem cells, red blood cells, white blood cells, and platelets.
TRANSPLANT: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS: Beginning on day - 3, patients receive tacrolimus IV or orally (PO) and
sirolimus PO once daily with taper per City of Hope standard operating procedure.
After completion of study treatment, patients are followed up on 30, 100, and 180 days, and
then yearly for 5 years.
Minimum age: 18 Years.
Maximum age: 70 Years.
Gender(s): Both.
Inclusion Criteria:
- Patients in 1st or 2nd remission with acute myeloid leukemia (AML) or acute
lymphoblastic leukemia (ALL) (no circulating blasts, < 5% myeloblasts in the bone
marrow, normalization of previously detected cytogenetic abnormalities, no
extramedullary disease )
- High risk myelodysplastic syndrome (MDS) (not myeloproliferative neoplasms)
- Intermediate II and high risk by International Prognostic Scoring System (IPSS)
- Intermediate, high, or very high by World Health Organization (WHO)
classification-based Prognostic Scoring System (WPSS)
- Transfusion dependent
- Therapy-related MDS or MDS evolved from previous hematological disorder
(excepting myelofibrosis)
- Patients with MDS that has evolved to AML must be in remission
- Patient must not be eligible for full ablative regimens by the attending physician
- Performance status of >= 70% on the Karnofsky scale
- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control or abstinence) prior to study entry and
for six months following duration of study participation; should a woman become
pregnant or suspect she is pregnant while participating on the trial, she should
inform her treating physician immediately
- Bone marrow and peripheral blood studies must be available for confirmation of
diagnosis; cytogenetics, flow cytometry, and molecular studies (such as fms-related
tyrosine kinase 3 [Flt-3] status) will be obtained as per standard practice
- Bone marrow aspirates/biopsies should be performed within 14 +/- 7 days from
registration to confirm disease remission status
- A pretreatment measured creatinine clearance (absolute value) of >= 60 mL/minute
- Patients must have a serum bilirubin =< 2. 0 mg/dl
- Patients must have serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate
pyruvate transaminase (SGPT) =< 2. 5 times the institutional upper limit of normal
- Ejection fraction measured by echocardiogram or multi gated acquisition scan (MUGA) >
50%
- Diffusing capacity of the lung for carbon monoxide (DLCO) or forced expiratory volume
in 1 second (FEV1) > 45% predicted
- Availability of an human leukocyte antigen (HLA) matched (6/6) sibling donor or 8/8
matched unrelated donor (no mismatch allowed in HLA-A, HLA-B, HLA-C and HLA-DR,
donors with mismatch HLA-DQ or HLA-DPH are eligible)
- Donor stem cell source can be either peripheral blood or bone marrow
- All patients must have a psychosocial evaluation prior to transplant as per City of
Hope (COH) standard operating procedure (SOP)
- All subjects must have the ability to understand and the willingness to sign a
written informed consent
- ALL or AML patients who received chemotherapy (induction or consolidation) can
proceed to transplant once bone marrow cellularity is > 10 % with no evidence of
leukemia
Exclusion Criteria:
- Patients who have received a prior autologous or allogeneic transplant are excluded
- Patients with significant hepatic dysfunction (not meeting liver function tests [LFT]
eligibility criteria)
- Patients with myelofibrosis or AML evolved from myelofibrosis
- Patients with MDS evolved into AML that is not in remission
- Patients with acute promyelocytic leukemia
- Patients with myeloproliferative neoplasms
- Patients with suspected or proven central nervous system (CNS) leukemia; (diagnostic
lumbar puncture not required before enrollment)
- Uncontrolled intercurrent illness including, but not limited to ongoing or active or
poorly controlled infection, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, poorly controlled pulmonary disease or psychiatric
illness/social situations that would limit compliance with study requirements
- Pregnant or lactating women are excluded from this study
- Patients who do not agree to practice effective forms of contraception
- Human immunodeficiency virus (HIV)-positive patients are excluded from this study
- Patients are excluded if they are hepatitis B surface antigen (sAg), hepatitis B (Hep
B) core antigen (cAg), Hep B core antibody (cAb), or hepatitis C (Hep C) positive
- Patients who have received radiation therapy as part of their leukemia treatment may
be ineligible and individual cases must be presented to the study principal
investigator (PI) for determination of eligibility
- Any psychiatric, social or compliance issues that, in the treating physician's
opinion, will interfere with completion of the transplant treatment and follow up
- Medical or psychiatric reasons which make the donor unlikely to tolerate or cooperate
with filgrastim (G-CSF) therapy or leukapheresis or bone marrow harvest
- Known allergies to clofarabine, melphalan, sirolimus or tacrolimus
- Patients with other active malignancies (besides AML, ALL, MDS) requiring treatment
or where there is concern of progression are ineligible for this study; however,
patients with previously treated skin cancer, early stage cervical or prostate cancer
may be eligible if there is no evidence of residual disease
- Cord blood as a donor source is not acceptable
- Subjects, who in the opinion of the investigator, may not be able to comply with the
safety monitoring requirements of the study