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Evomela Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation (AutoSCT) for Multiple Myeloma (MM)

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ClinicalTrials.gov Identifier: NCT03417284
Recruitment Status : Not yet recruiting
First Posted : January 31, 2018
Last Update Posted : December 25, 2018
Sponsor:
Collaborator:
Spectrum Pharmaceuticals, Inc
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to find the recommended dose level and dosing schedule of Evomela that can help prevent multiple myeloma from coming back in patients who are receiving an autologous stem cell transplant. The safety of using this drug before a transplant will also be studied.

This is an investigational study. Evomela is FDA approved and commercially available for use before stem cell transplants. It is investigational to compare different dosing schedules of the drug and to use a higher dose of Evomela than the FDA approved dose.

The study doctor can describe how Evomela is designed to work.

Up to 60 participants will be enrolled in this study. All will take part at MD Anderson.


Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Evomela Procedure: Autologous Stem Cell Infusion Drug: G-CSF Drug: Palifermin Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prospective Phase I/II Trial to Jointly Optimize the Administration Schedule(s) and Dose(s) of Melphalan for Injection (Evomela) as a Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation in Patients With Newly Diagnosed Multiple Myeloma
Estimated Study Start Date : February 2019
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : August 2020


Arm Intervention/treatment
Experimental: Group 1: Evomela For 30 Minutes to 60 minutes

Participants receive Evomela by vein over 30 to 60 minutes on Day -2. The first sets of participants receive the lowest dose level. Each new set receives a higher dose than the set before it, if no intolerable side effects were seen. This continues until the highest tolerable dose of Evomela is found.

Participants receive Palifermin by vein on Days -5, -4, -3, +1, +2, and +3.

On Day 0, participants receive the stem cell transplant by vein over about 30-60 minutes.

Starting on Day +5, participants receive G-CSF (filgrastim) as an injection just under the skin.

Drug: Evomela

Group 1 Evomela Starting Dose: 200 mg/m2 by vein for 30 minutes on Day -2.

Group 2 Evomela Starting Dose: 200 mg/m2 by vein for 12 hours on Day -2.

Phase II starting dose is maximum tolerated dose from Phase I.

Other Names:
  • Melphalan
  • Alkeran

Procedure: Autologous Stem Cell Infusion
Autologous Stem Cell Infusion on Day 0.

Drug: G-CSF
G-CSF 5 mcg/kg/day (rounded up to the nearest vial, max dose of 600 mcg) given subcutaneously on Day +5, continuing until evidence of an absolute neutrophil count (ANC) of 0.5 x 109/L.
Other Names:
  • Filgrastim
  • Neupogen

Drug: Palifermin
Palifermin 60 microgram/Kg by vein over about 30 seconds on Days -5, -4, -3, +1, +2, and +3.
Other Name: Kepivance

Experimental: Group 2: Evomela For 8 to 9 Hours

Participants receive Evomela by vein over 8 to 9 hours on Day -2. The first sets of participants receive the lowest dose level. Each new set receives a higher dose than the set before it, if no intolerable side effects were seen. This continues until the highest tolerable dose of Evomela is found.

Participants receive Palifermin by vein on Days -5, -4, -3, +1, +2, and +3.

On Day 0, participants receive the stem cell transplant by vein over about 30-60 minutes.

Starting on Day +5, participants receive G-CSF (filgrastim) as an injection just under the skin.

Drug: Evomela

Group 1 Evomela Starting Dose: 200 mg/m2 by vein for 30 minutes on Day -2.

Group 2 Evomela Starting Dose: 200 mg/m2 by vein for 12 hours on Day -2.

Phase II starting dose is maximum tolerated dose from Phase I.

Other Names:
  • Melphalan
  • Alkeran

Procedure: Autologous Stem Cell Infusion
Autologous Stem Cell Infusion on Day 0.

Drug: G-CSF
G-CSF 5 mcg/kg/day (rounded up to the nearest vial, max dose of 600 mcg) given subcutaneously on Day +5, continuing until evidence of an absolute neutrophil count (ANC) of 0.5 x 109/L.
Other Names:
  • Filgrastim
  • Neupogen

Drug: Palifermin
Palifermin 60 microgram/Kg by vein over about 30 seconds on Days -5, -4, -3, +1, +2, and +3.
Other Name: Kepivance




Primary Outcome Measures :
  1. Toxicity of Evomela Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation (AutoSCT) for Multiple Myeloma (MM) [ Time Frame: Within 30 days from start of infusion. ]
    Toxicity defined as grade 3 mucositis lasting > 3 days, grade 4 mucositis, or any grade 4 or 5 non-hematologic or non-infectious toxicity.


Secondary Outcome Measures :
  1. Incidence of Treatment Related Mortality (TRM) After Auto-HCT in Newly Diagnosed Myeloma Patients Treated on Different Schedules and Doses of Evomela [ Time Frame: 90 days after stem cell infusion ]
  2. Rate of Minimal Residual Disease (MRD) After Auto-HCT in Newly Diagnosed Myeloma Patients Treated on Different Schedules and Doses of Evomela [ Time Frame: 90 days after stem cell infusion ]
    MRD defined as absence of phenotypically aberrant clonal plasma cells by nerve growth factor (NGF) on bone marrow aspirates using the EuroFlow standard operation procedure for MRD detection in multiple myeloma (or validated equivalent method) with a minimum sensitivity of 1 in 105 nucleated cells or higher.

  3. Progression-Free Survival (PFS) After Auto-HCT in Newly Diagnosed Myeloma Patients Treated on Different Schedules and Doses of Evomela [ Time Frame: Up to 1 year after stem cell transplant ]
  4. Overall Survival (OS) After Auto-HCT in Newly Diagnosed Myeloma Patients Treated on Different Schedules and Doses of Evomela [ Time Frame: Up to 1 year after stem cell transplant ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with multiple myeloma in complete response (CR), partial remission (PR), very good partial remission (VGPR), or symptomatic stable disease (no evidence of progression) including patients with light chain MM detected in the serum by free light chain assay.
  2. Patients with non-secretory multiple myeloma [absence of a monoclonal protein (M protein) in serum as measured by electrophoresis (SPEP) and immunofixation (SIFE) and the absence of Bence Jones protein in the urine (UPEP) defined by use of conventional electrophoresis and immunofixation (UIFE) techniques] but with measurable disease on imaging studies like MRI, CT scan or PET scan.
  3. Patients who have received at least two cycles of initial systemic therapy and are within 2 to 12 months of the first dose. Mobilization therapy is not considered initial therapy.
  4. Age 18 - 70 years.
  5. Karnofsky performance score 70% or higher.
  6. Cardiac function: left ventricular ejection fraction at rest > 40% within 3 months of registration.
  7. Hepatic function: bilirubin < 2x the upper limit of normal (except patients with Gilbert Syndrome in whom bilirubin level of >2x upper normal limit will be allowed) and ALT and AST < 2.5x the upper limit of normal.
  8. Renal function: creatinine clearance of >/= 40 mL/min, estimated or calculated using the Cockcroft-Gault equation.
  9. Pulmonary function: DLCO, FEV1, FVC > 50% of predicted value (corrected for hemoglobin) within 3 months of registration.
  10. All female and male subjects of reproductive potential must consent to the use of effective contraceptive methods as advised by the study doctor during treatment.
  11. Signed informed consent form.

Exclusion Criteria:

  1. Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and progression of clinical symptoms).
  2. Patients seropositive for the human immunodeficiency virus (HIV).
  3. Patients with history of myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
  4. Patients participating in an investigational new drug protocol within 14 days before enrollment.
  5. Female patients who are pregnant (positive b-HCG) or breast feeding.
  6. Prior hematopoietic cell transplantation allogeneic or autologous (A prior autologous HCT will be allowed as long as it was part of tandem transplantation).
  7. Prior organ transplant requiring immunosuppressive therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03417284


Contacts
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Contact: Qaiser Bashir, MD 713-792-8750 qbashir@mdanderson.org

Locations
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United States, Texas
University of Texas MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Contact       qbashir@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
Spectrum Pharmaceuticals, Inc
Investigators
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Principal Investigator: Qaiser Bashir, MD M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03417284     History of Changes
Other Study ID Numbers: 2017-0399
NCI-2018-00906 ( Registry Identifier: NCI CTRP )
First Posted: January 31, 2018    Key Record Dates
Last Update Posted: December 25, 2018
Last Verified: December 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by M.D. Anderson Cancer Center:
Multiple Myeloma
MM
Evomela
Melphalan
Alkeran
G-CSF
Filgrastim
Neupogen
Stem cell transplant

Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Lenograstim
Melphalan
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Immunosuppressive Agents