Clofarabine, Melphalan, and Thiotepa Followed By a Donor Stem Cell Transplant in Treating Patients With High-Risk and/or Advanced Hematologic Cancer or Other Disease

NCT00423514 | Completed Phase 1 Results

• 2 other identifiers: 06-125MSKCC-06125
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Giving chemotherapy, such as clofarabine, melphalan, and thiotepa, 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 also make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil before the transplant may stop this from happening. PURPOSE: This phase I/II trial is studying the side effects and best dose of clofarabine when given together with melphalan and thiotepa, followed by a donor stem cell transplant and to see how well it works in treating patients with high-risk and/or advanced hematologic cancer or other disease.

Conditions

Graft Versus Host Disease; Leukemia; Myelodysplastic Syndromes

Keywords

graft versus host disease; adult acute lymphoblastic leukemia in remission; adult acute myeloid leukemia in remission; childhood acute lymphoblastic leukemia in remission; childhood chronic myelogenous leukemia; recurrent childhood acute myeloid leukemia; accelerated phase chronic myelogenous leukemia; acute undifferentiated leukemia; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; blastic phase chronic myelogenous leukemia; juvenile myelomonocytic leukemia; previously treated myelodysplastic syndromes; recurrent adult acute lymphoblastic leukemia; recurrent adult acute myeloid leukemia; relapsing chronic myelogenous leukemia; secondary acute myeloid leukemia; secondary myelodysplastic syndromes; childhood acute myeloid leukemia in remission; de novo myelodysplastic syndromes; recurrent childhood acute lymphoblastic leukemia; chronic phase chronic myelogenous leukemia; 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); childhood myelodysplastic syndromes

Outcome Measures

Primary Outcomes (2)

• Response to Therapy

  * A complete response (CR) will be defined as less than 5% bone marrow blasts in the setting of a neutrophil count of \>/= 1.0 K/ul and a platelet count of \>/= 75,000/ul * A complete response except platelets (CRp) will be defined as less than 5% bone marrow blasts in the setting of a neutrophil count of \>/= 1.0 K/ul and a platelet count of \>/= 75,000/ul * A partial response (PR) will be defined as 5%-25% bone marrow blasts in the setting of a neutrophil count of \>/= 1.0 K/ul and a platelet count of \>/= 75,000/ul * A partial response except platelets (PRp) will be defined as 5%-25% bone marrow blasts in the setting of a neutrophil count of \>/= 1.0 K/ul and a platelet count of \>/= 75,000/ul

  1 year

• Overall Survival

  1 year

Secondary Outcomes (1)

• Participants Evaluated for Early Post-transplant Regimen-related Severe Morbidity (Grade III to IV Nonhematologic Toxicity) and Mortality as Measured by the NCI Cancer Therapy Evaluation Program CTCAE v 3.0

  1 year

Study Arms (1)

cytoreduction regimen & stem cell transplant

EXPERIMENTAL

This is a single arm phase I/II clinical trial to assess efficacy (the antileukemic potential and relapse rate), and safety (peri-transplant morbidity and mortality) of a novel cytoreduction regimen in preparation for allogeneic hematopoietic stem cell transplantation (HSCT).

Biological: filgrastim; Drug: clofarabine; Drug: melphalan; Drug: mycophenolate mofetil; Drug: tacrolimus; Drug: thiotepa; Procedure: allogeneic bone marrow transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation

Interventions

filgrastim BIOLOGICAL

cytoreduction regimen & stem cell transplant

clofarabine DRUG

cytoreduction regimen & stem cell transplant

melphalan DRUG

cytoreduction regimen & stem cell transplant

mycophenolate mofetil DRUG

cytoreduction regimen & stem cell transplant

tacrolimus DRUG

cytoreduction regimen & stem cell transplant

thiotepa DRUG

cytoreduction regimen & stem cell transplant

allogeneic bone marrow transplantation PROCEDURE

cytoreduction regimen & stem cell transplant

allogeneic hematopoietic stem cell transplantation PROCEDURE

cytoreduction regimen & stem cell transplant

peripheral blood stem cell transplantation PROCEDURE

cytoreduction regimen & stem cell transplant

Eligibility Criteria

• Age: 0 Years - 54 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed diagnosis of 1 of the following: * Acute myelogenous leukemia, meeting 1 of the following criteria: * In first complete remission (CR), meeting 1 of the following criteria: * Poor risk \[no t(15,17), inv 16, or t(8,21)\] * Not a candidate for total body irradiation (TBI) * Any infant in first CR * In second CR, meeting the following criteria: * All patients * In more than second CR OR relapsed/refractory disease, meeting the following criteria: * All patients * Blast percentage \> 5% and \< 25% in bone marrow (BM) at the time of stem cell transplantation (SCT) * Acute lymphoblastic leukemia, meeting 1 of the following criteria: * In first CR, meeting 1 of the following criteria: * Poor risk \[t(9;22), t(4;11) AND no CR after 7-28 days of induction\] * Not a candidate for TBI * Any infant in first CR * In second CR, meeting the following criteria: * All patients * In more than second CR OR relapsed/refractory disease, meeting the following criteria: * All patients * Blast percentage \> 5% and \< 25% in BM at the time of SCT * Acute undifferentiated or biphenotypic leukemia, meeting the following criteria: * All patients * Blast percentage \> 5% and \< 25% in BM at the time of SCT * Chronic myelogenous leukemia, meeting the following criteria: * All patients * In first chronic phase * Myelodysplastic syndrome, meeting 1 of the following criteria: * Primary high risk disease * Stage \> RAEB1 * Secondary high risk disease * All patients * Any stage * Juvenile myelomonocytic leukemia * All patients * No doubling of peripheral blast counts within a period of 2 weeks * No active CNS disease * HLA-compatible donor available meeting 1 of the following criteria: * Related donor * Genotypically or phenotypically matched at ≥ 7 or 8 of HLA-A, -B, -C and -DRB1 alleles * Unrelated donor meeting 1 of the following criteria: * 8 of 8 alleles matched * For patients \< 18 years old only: 7 or 8 alleles matched with the mismatch at only 1 HLA-A, -B, -C, or -DRB1 allele * Two HLA-compatible unrelated cord blood (UCB) units available meeting the following criteria: * HLA-matched minimally at 4 of 6 HLA-A, HLA-B, and DRB1 allele * HLA-A and HLA-B matched at intermediate resolution by molecular technique * DRB1 allele matched at high resolution by molecular technique * Both matched UCB units with cryopreserved nucleated cell dose ≥ 1.5 x 10\^7/kg PATIENT CHARACTERISTICS: * Karnofsky OR Lansky performance status 70-100% * SGOT \< 2 times upper limit of normal * Bilirubin \< 1.5 mg/dL (unless there is liver disease involvement) * Creatinine normal OR creatinine clearance \> 60 mL/min * LVEF \> 50% at rest OR shortening fraction ≥ 29% * Patients with asymptomatic pulmonary disease with no prior risk factors OR symptomatic pulmonary disease with diffusion capacity \> 50% of predicted (corrected for hemoglobin) are eligible * No active uncontrolled viral, bacterial, or fungal infection * No known HIV I or II positivity * No known human T-cell lymphotrophic virus I or II positivity * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: * No hydroxyurea within the past 2 weeks * No allogeneic or autologous stem cell transplantation within the past 6 months

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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Graft vs Host Disease; Leukemia; Myelodysplastic Syndromes; Leukemia, Myeloid, Accelerated Phase; Leukemia, Biphenotypic, Acute; Congenital Abnormalities; Blast Crisis; Leukemia, Myelomonocytic, Juvenile; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Myeloid, Chronic-Phase

Interventions

Filgrastim; Clofarabine; Melphalan; Mycophenolic Acid; Tacrolimus; Thiotepa; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Myelodysplastic-Myeloproliferative Diseases

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; 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; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Farid Boulad, MD
• Organization: Memorial Sloan Kettering Cancer Center

bouladf@MSKCC.ORG

1-833-MSK-KIDS

Study Officials

• Farid Boulad, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: January 16, 2007
• First Posted: January 18, 2007
• Study Start: November 20, 2006
• Primary Completion: June 18, 2021
• Study Completion: June 18, 2021
• Last Updated: December 27, 2022
• Results First Posted: December 27, 2022

Record last verified: 2021-06

Locations

US (1)