Clofarabine and High-Dose Melphalan Followed by Donor Stem Cell Transplant in Patients With Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Myelodysplastic Syndromes

NCT00641030 | Completed Phase 1 DMC

• 4 other identifiers: 06114P30CA033572CHNMC-06114CDR0000589304
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Leukemia; Myelodysplastic Syndromes

Keywords

de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; adult acute lymphoblastic leukemia in remission; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); adult acute myeloid leukemia in remission; recurrent adult acute myeloid leukemia; childhood acute myeloid leukemia in remission; recurrent childhood acute myeloid leukemia; secondary acute myeloid leukemia; childhood myelodysplastic syndromes; recurrent adult acute lymphoblastic leukemia; recurrent childhood acute lymphoblastic leukemia; childhood acute lymphoblastic leukemia in remission

Outcome Measures

Primary Outcomes (3)

• 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

Secondary Outcomes (2)

• Efficacy

  One year post-transplant

• Correlative laboratory studies of engraftment, immune reconstitution, and therapeutic outcomes

  One year post-transplant

Interventions

clofarabine DRUG

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 DRUG

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 GENETIC

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

reverse transcriptase-polymerase chain reaction GENETIC

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

flow cytometry OTHER

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 OTHER

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 PROCEDURE

Infusion of allogeneic hematopoietic stem cells on day 0 of transplant

Eligibility Criteria

• Age: 1 Year - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010-3000, United States

Location

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Congenital Abnormalities; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Clofarabine; Melphalan; Gene Expression Profiling; Reverse Transcriptase Polymerase Chain Reaction; Flow Cytometry

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Leukemia, Myeloid; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Genetic Techniques; Investigative Techniques; Polymerase Chain Reaction; Nucleic Acid Amplification Techniques; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical

Study Officials

• Anthony Stein, MD

  City of Hope Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2008
• First Posted: March 21, 2008
• Study Start: July 1, 2007
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: June 15, 2023

Record last verified: 2023-06

Locations

US (1)