Study of Melphalan and Topotecan (MT) Followed by Autologous Stem Cell Rescue in Patients With Multiple Myeloma.

NCT00325416 | Completed Phase 1 Results DMC

• 1 other identifier: MCC-12733
• Study Type: interventional
• Target: 177
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to determine the safest dose of topotecan when given in a high dose before a stem cell transplant; topotecan will be given with melphalan.

Conditions

Multiple Myeloma

Keywords

melphalan; topotecan; topoisomerase; bone marrow transplant; drug sequence

Outcome Measures

Primary Outcomes (2)

• Phase I - Maximum Tolerated Dose (MTD) Level

  MTD of topotecan in multiple myeloma patients receiving autologous transplant when give with melphalan 150 mg/m\^2 for three days. Two parallel dose escalations were used, one each for young (18-60 years of age) and elderly patients (\> 61 years of age). Elderly patients began a dose level once it had been found to be safe for the young cohort. The purpose of this approach was to expand the access of this trial to elderly patients while ensuring safety. Phase I Dose Escalation: Level 1 - 20 mg/m\^2; Level 2 - 30 mg/m\^2; Level 4 - 54 mg/m\^2; Level 5 - 72 mg/m\^2; Level 6 - 96 mg/m\^2; Level 7 - 127.8 mg/m\^2; Level 8 - 170.1 mg/m\^2

  Phase I - 5 years, 2 months

• Phase II Participants - Overall Response Rate

  Re-evaluation of participants who had responsive disease prior to transplant. All changes in monoclonal protein and immunoglobulins will be referenced to those levels obtained immediately prior to cyclophosphamide priming chemotherapy. Complete Response (CR): A CR will be defined as the disappearance of the monoclonal protein by immunofixation studies of serum and urine (100x concentrate) and less than or equal to 5% plasma cells in a bone marrow aspirate. Partial Response (PR): 50% - 74% decrease in the measurable monoclonal protein (M-component from an SPEP and/or UPEP with immunofixation).

  Phase II - Phase start at 62 months up to 120 months

Secondary Outcomes (2)

• Phase II Event Free Survival (EFS)

  Phase II - Phase start at 62 months up to 120 months

• Phase II Overall Survival (OS)

  Phase II - Phase start at 62 months up to 120 months

Other Outcomes (5)

• Pharmacokinetic Profiles of High Dose Topotecan and Melphalan

  Predetermined time points in protocol

• Amount, Activity and Subcellular Distribution of Topoisomerase I With Clinical Response and Toxicity

  Laboratory study (no specific time points)

• DNA Topoisomerase I Amount, Activity, or Subcellular Distribution

  Laboratory study (N/A)

Study Arms (2)

Age Group A - Melphalan and Topotecan plus Stem Cell Rescue

EXPERIMENTAL

Participants 18 - 60 years of age. Intensive-Dose Melphalan and Topotecan (MT) followed by Stem Cell transplant.

Drug: melphalan; Drug: topotecan (TPT); Procedure: Autologous Stem Cell Rescue

Age Group B - Melphalan and Topotecan plus Stem Cell Rescue

ACTIVE COMPARATOR

Participants 61 years of age or older. Intensive-Dose Melphalan and Topotecan (MT) followed by Stem Cell transplant.

Drug: melphalan; Drug: topotecan (TPT); Procedure: Autologous Stem Cell Rescue

Interventions

melphalan DRUG

(Days -4,-3,-2) 50 mg/m\^2/day IV over 30 minutes (total dose 150 mg/m\^2)

Also known as: Alkeran®

Age Group A - Melphalan and Topotecan plus Stem Cell Rescue; Age Group B - Melphalan and Topotecan plus Stem Cell Rescue

topotecan (TPT) DRUG

Phase I Dose Escalation: Level 1 - 20 mg/m\^2; Level 2 - 30 mg/m\^2; Level 4 - 54 mg/m\^2; Level 5 - 72 mg/m\^2; Level 6 - 96 mg/m\^2; Level 7 - 127.8 mg/m\^2; Level 8 - 170.1 mg/m\^2 Phase II: Treatment at maximum tolerated dose (MTD)

Also known as: Hycamtin®

Age Group A - Melphalan and Topotecan plus Stem Cell Rescue; Age Group B - Melphalan and Topotecan plus Stem Cell Rescue

Autologous Stem Cell Rescue PROCEDURE

Day 0

Also known as: Bone Marrow Transplant, Stem Cell Transplant

Age Group A - Melphalan and Topotecan plus Stem Cell Rescue; Age Group B - Melphalan and Topotecan plus Stem Cell Rescue

Eligibility Criteria

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

You may qualify if:

• Multiple Myeloma Criteria = Newly diagnosed with drug sensitive disease (\>50% tumor response to standard chemotherapy) and poor prognostic indicators, such as Salmon-Durie stage III, serum b-2-microglobulin \>3.0 mg/L, high proliferative fraction or hypodiploidy. Relapsed patients after a response to standard chemotherapy. Patients with primary refractory disease. Patients with non-secretory multiple myeloma are eligible for enrollment on this study. They will be followed for toxicity, survival and molecular endpoint analyses, but will not be followed for response. Patients with plasma cell leukemia, either occurring de novo or arising from existing multiple myeloma, are ineligible for this study.
• Patients greater than or equal to 18 years of age are eligible.
• Patients must have histologically confirmed diagnosis by a pathologic review at the H. Lee Moffitt Cancer Center and Research Institute.
• Patients must have undergone a complete psychosocial evaluation and been considered capable of compliance.
• Patients willing and able to receive palifermin (young cohort only)

You may not qualify if:

• Patients with a diffusing lung capacity oxygenation (DLCO) less than 50% (adjusted) of normal or with symptomatic obstructive or restrictive disease are ineligible.
• Patients with a serum creatinine of greater than 2.0 mg/dL OR a creatinine clearance of less than 40 ml/minute. Creatinine clearance can be measured or calculated. Patients with renal dysfunction secondary to multiple myeloma may be enrolled at the discretion of the principal investigator. However, patients on hemodialysis or peritoneal dialysis are ineligible.
• Patients with a total bilirubin greater than 2.0 mg/dL and serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) greater than two and a half times normal (unless due to primary malignancy), or a history of severe hepatic dysfunction are ineligible.
• Patients who have evidence of severe cardiac dysfunction are ineligible. A gated blood pool (MUGA) scan must show an ejection fraction of at least 50%. Patients must be free of major heart disease. Patients are ineligible if they have received a total dose of doxorubicin of greater than 450 mg/m2 (or daunorubicin equivalent) unless the left ventricular ejection fraction by MUGA scan is at least 50%. Patients must not be taking nitroglycerin preparations for angina pectoris or antiarrhythmic drugs for major ventricular dysrhythmias. Patients with essential hypertension controlled with medications are eligible for study. Any patient with congenital or acquired heart disease or cardiac arrhythmias will have a cardiology consult and evaluation.
• Patients with active infections are ineligible.
• Patients who are HIV antibody positive are ineligible.
• Patients with active leptomeningeal involvement are ineligible. Patients with a history of previous cerebrospinal fluid (CSF) tumor involvement without symptoms or signs are eligible provided the CSF is now free of disease on lumbar puncture and MRI of the brain shows no tumor involvement. Patients with severe symptomatic central nervous system (CNS) disease of any etiology are ineligible.
• Patients with uncontrolled insulin-dependent diabetes mellitus or uncompensated major thyroid or adrenal dysfunction are ineligible.
• Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of \> or = 2 are ineligible. Patients with ECOG performance status 2 to 3 secondary to bone pain may be enrolled at the discretion of the institutional investigator. Patients with ECOG performance status 2 to 3 secondary to a potentially reversible disease-related problem may be enrolled at the discretion of the institutional investigator.
• Patients who are pregnant or lactating are ineligible.
• Patients with any previous malignancy other than non-melanoma skin cancer are ineligible, unless the patient is without evidence of disease \> or = 5 years after the treatment for the cancer was completed.
• Patients previously treated with topotecan or any other topoisomerase I inhibitor.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• GlaxoSmithKline: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Related Links

• H. Lee Moffitt Cancer Center \& Research Institute

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Melphalan; Topotecan; Bone Marrow Transplantation; Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System 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; Camptothecin; Alkaloids; Heterocyclic Compounds; Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Cell Transplantation

Limitations and Caveats

Data on presence of chromosomal abnormalities at time of diagnosis were not available for majority of patients. The cancer center will continue to collect information about the participant's disease and its treatment for the rest of their life.

Results Point of Contact

• Title: Daniel M. Sullivan, M.D.
• Organization: H. Lee Moffitt Cancer Center and Research Institute

dan.sullivan@moffitt.org

813-745-3878

Study Officials

• Daniel M Sullivan, MD

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2006
• First Posted: May 12, 2006
• Study Start: November 19, 2001
• Primary Completion: July 15, 2013
• Study Completion: January 30, 2018
• Last Updated: March 14, 2018
• Results First Posted: May 23, 2014

Record last verified: 2018-02

Locations

US (1)