Clinical trial

A Phase I Study of Clofarabine Plus High Dose Melphalan as a Conditioning Regimen for Allogeneic Transplantation

Name

06114

Description

RATIONALE: Giving chemotherapy, such as clofarabine and melphalan, before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. PURPOSE: This phase I trial is studying the side effects and best dose of clofarabine when given together with high-dose melphalan followed by a donor stem cell transplant in treating patients with acute myeloid leukemia, acute lymphocytic leukemia, or myelodysplastic syndromes.

Trial arms

Trial start

2007-07-01

Estimated PCD

2011-01-01

Trial end

2011-01-01

Status

Completed

Phase

Early phase I

Treatment

clofarabine

Administered at the appropriate dose level(dose level one = 30 mg/m2, dose level two and three = 40 mg/m2)on days -9 to day -5 from transplant

melphalan

Administered at the appropriate dose level (dose level one and two = 100 mg/m2, dose level three = 140 mg/m2) on day -4 from transplant

gene expression analysis

Peripheral blood draw on day -9 and day -4 prior to transplant

reverse transcriptase-polymerase chain reaction

Peripheral blood draw on day -9 and day -4 prior to transplant

flow cytometry

Bone marrow aspirate and biopsy to confirm diagnosis prior to transplant, day -9 pre-transplant, day 30 post-transplant, day 100 post-transplant, 6 months post-transplant, one year post-transplant, then yearly through year 5 post-transplant

laboratory biomarker analysis

Peripheral blood draw day -9 or earlier pre-transplant, day 14 post-transplant, day 30 post-transplant, day 60 post-transplant, day 100 post-transplant, 6 months and one year post-transplant.

allogeneic hematopoietic stem cell transplantation

Infusion of allogeneic hematopoietic stem cells on day 0 of transplant

Size

Primary endpoint

Maximum tolerated dose

4 weeks from the start of treatment

Dose-limiting toxicity as assessed by NCI CTCAE v3.0 and the Modified Bearman scale

4 weeks from the start of treatment

Graft failure or rejection

35 days post-transplant

Eligibility criteria

DISEASE CHARACTERISTICS: * Diagnosis of one of the following: * Acute myeloid leukemia * Acute lymphocytic leukemia * Myelodysplastic syndromes * Disease meets 1 of the following criteria: * In first complete remission (CR) * In second CR * In relapse * No more than 50% blasts in bone marrow * Not deemed eligible for standard transplantation regimens by the attending physician, or at high risk for relapse * No suspected or proven CNS leukemia * HLA-matched (6/6) sibling donor available PATIENT CHARACTERISTICS: * Karnofsky performance status 50-100% * Glomerular filtration rate (pediatric patients) or creatinine clearance ≥ 60 mL/min OR serum creatinine \< 1.5 times upper limit of normal (ULN) * Serum bilirubin ≤ 2.0 mg/dL * AST and ALT ≤ 2.5 times ULN * LVEF ≥ 50% by ECHO or MUGA scan * DLCO or FEV_1 ≥ 40% predicted * Not pregnant * Negative pregnancy test * No concurrent uncontrolled illness including, but not limited to, any of the following: * Ongoing, active, or poorly controlled infection * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia * Poorly controlled pulmonary disease * Psychiatric illness/social situation that would limit compliance with study requirement * No active cytomegalovirus (CMV) or fungal disease * HIV negative PRIOR CONCURRENT THERAPY: * Recovered from prior intensive chemotherapy (pediatric patients) * At least 100 days since prior autologous stem cell transplantation * At least 100 days since prior radiotherapy administered as part of a transplantation conditioning regimen * At least 4 weeks since prior chemotherapy * At least 24 hours since prior hydroxyurea for blast count control

Protocol

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Updated at

2023-06-15

1 organization

4 products

2 indications

Organization

City of Hope Medical Center

Product

clofarabine

Indication

Leukemia

Indication

Myelodysplastic Syndromes

Product

melphalan

Product

Gene Expression Analysis

Product

Reverse Transcriptase-Polymerase Chain Reaction