Low Dose Melphalan and Bortezomib for AML and High-Risk MDS

NCT00789256 | Completed Results DMC

• 1 other identifier: D0337
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine the response rate of the combination of bortezomib and melphalan in patients with Acute Myelogenous Leukemia (AML) or high-risk Myelodysplastic Syndromes (MDS).

Conditions

Acute Myelogenous Leukemia; Myelodysplastic Syndromes

Keywords

Acute Myelogenous Leukemia; AML; Myelodysplastic Syndromes; MDS; Melphalan; Bortezomib; Velcade

Outcome Measures

Primary Outcomes (1)

• Response Rate of the Combination of Bortezomib and Melphalan in Patients With AML and High-risk MDS.

  Determine disease response to treatment using Cheson 2000 report of an international working group to standardize response criteria for myelodysplastic syndromes.

  Post Cycle 1 through 28 days post-treatment

Secondary Outcomes (2)

• Determine Safety Profile of the Combination of Bortezomib and Melphalan.

  Start of treatment through 28 days post-treatment

• Number of Participants With Correlation Between in Vitro and in Vivo Activity of the Combination of Bortezomib and Melphalan.

  Pre-treatment and at complete response

Study Arms (1)

Study treatment

EXPERIMENTAL

All patients will receive the following regimen: 1) Melphalan 2 mg orally, once daily. 2) Bortezomib 1.0 mg/M2 IV on days 1, 4, 8, 11.

Drug: Melphalan; Drug: Bortezomib; Drug: Melphalan and bortezomib

Interventions

Melphalan DRUG

Melphalan: 2mg orally, once daily

Also known as: Velcade

Study treatment

Bortezomib DRUG

Bortezomib: 1.0mg/M2 IV on days 1, 4, 8, 11

Study treatment

Melphalan and bortezomib DRUG

Study treatment

Eligibility Criteria

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

You may qualify if:

• Pathologic diagnosis of AML or high-risk MDS Patients with chronic myelomonocytic leukemia or a refractory cytopenia with multilineage dysplasia are eligible if that have one of the following criteria:
• \>4 units of red blood cells transfused during the previous 3 months
• platelet count \<50,000/uL
• absolute neutrophil count \<1000/uL and a recent infection requiring antibiotics
• Patients may either be considered to be poor candidates for standard induction chemotherapy based on reasonable medical evidence or have declined such therapy, but still desire palliative treatment beyond that of best supportive care
• Primary refractory disease or have disease that has relapsed after prior cytoxic therapy
• Karnofsky performance status of \>50%
• Patients may receive prior growth factor therapy
• Patients who received prior therapies (ex. melphalan, 5-azacitidine, low-dose cytarabine) to control their MDS or AML prior to registration (Stratum 2), but are clearly nonresponders are eligible for enrollment if expected toxicity of the prior therapy has resolved
• Voluntary written informed consent
• If female, the subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study
• If male, the subject agrees to use an acceptable method for contraception for the duration of the study
• Patients that have been previously treated will be eligible for study if:
• the previous therapy was ineffective and
• all expected toxicity of the previous treatment has resolved

You may not qualify if:

• AML FAB M3
• No concomitant malignancy other than a curatively treated carcinoma in situ of cervix or basal or squamous cell carcinoma of the skin
• Active, uncontrolled infections
• Chronic liver disease not due to AML, or bilirubin \>2.0mg/dL
• End stage kidney disease on dialysis
• Active CNS disease. A lumbar puncture prior to treatment is not required and should not be performed in the absence of significant CNS symptoms or signs
• Patient has sensory peripheral neuropathy \> grade 2 or painful peripheral neuropathy \> grade 1 (see appendix A for NCI sensory neuropathy toxicity criteria) within 14 days before enrollment
• Hypersensitivity to bortezomib, boron or mannitol
• Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (2)

Integrated Community Oncology Network

Jacksonville, Florida, 32256, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

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  BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Melphalan; Bortezomib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Marc Gautier, MD - Principal Investigator
• Organization: Dartmouth-Hitchcock Medical Center

marc.gautier@hitchcock.org

603-650-5529

Study Officials

• Marc Gautier, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

• Jeffrey Bubis, DO

  Integrated Community Oncology Network

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Director, Regional Affairs at Norris Cotton Cancer Center

Study Record Dates

• First Submitted: October 6, 2008
• First Posted: November 11, 2008
• Study Start: September 1, 2004
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: October 24, 2018
• Results First Posted: July 22, 2013

Record last verified: 2018-10

Locations

US (2)