Vaccine Therapy With or Without Cyclophosphamide in Treating Patients With Recurrent or Refractory Multiple Myeloma

NCT00450814 | Completed Phase 1 Results DMC

• 5 other identifiers: MC038CNCI-2009-01194P30CA015083R01CA125614R01CA168719
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and best dose of vaccine therapy when given with or without cyclophosphamide and to see how well they work in treating patients with multiple myeloma that has come back (recurrent) or has not responded to previous treatment (refractory). Vaccines made from a gene-modified virus may help the body build an effective immune response to kill cancer cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving vaccine therapy together with cyclophosphamide may be a better treatment for multiple myeloma.

Conditions

Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (3)

• Number of Phase I Participants With Dose-Limiting Toxicity Events (Phase I)

  The Maximum Tolerated Dose (MTD) is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Dose-limiting toxicities include non-hematologic events graded 3 or higher and deemed at least possibly related to treatment. A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD. The number of patients reporting a dose-limiting event are reported.

  6 weeks

• Maximum Tolerated Dose (MTD) (Phase I)

  The Maximum Tolerated Dose (MTD) is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Dose-limiting toxicities include non-hematologic events graded 3 or higher and deemed at least possibly related to treatment. A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD. The MTD is reported below.

  6 weeks

• Proportion of Confirmed Response, Defined as a Partial Response (PR) or Better (Phase II)

  Confirmed response will be evaluated using all cycles. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

  Up to 1 year

Secondary Outcomes (9)

• Overall Toxicity Rate, Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0) (Phase I)

  Up to 1 year

• Number of Patients With Clinical Responses (Phase I)

  Up to 1 year

• Overall Survival (Phase II)

  Time from registration to death due to any cause, assessed up to 1 year

• Time to Progression (TTP) (Phase II)

  Time from registration to the earliest date with documentation of disease progression, assessed up to 1 year

• Progression-free Survival (Phase II)

  At 1 year

Other Outcomes (8)

• Time Until Any Treatment Related Toxicity (Phase I)

  Up to 1 year

• Time Until Hematologic Nadirs (White Blood Cells, ANC, Platelets) (Phase I)

  Up to 1 year

• Time Until Treatment Related Grade 3+ Toxicity (Phase I)

  Up to 1 year

Study Arms (2)

Stage 1 (MV-NIS alone)

EXPERIMENTAL

Patients receive MV-NIS IV over 1 hour on day 1. (Closed to accrual on 12/17/2009 and reopened 10/13/2011)

Other: Laboratory Biomarker Analysis; Biological: Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter; Other: Pharmacological Study

Stage 2 (MV-NIS and cyclophosphamide)

EXPERIMENTAL

Patients receive cyclophosphamide IV over 30 minutes and then MV-NIS IV over 1 hour 2 days later. (Temporarily closed to accrual on 10/13/11)

Drug: Cyclophosphamide; Other: Laboratory Biomarker Analysis; Biological: Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter; Other: Pharmacological Study

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Stage 2 (MV-NIS and cyclophosphamide)

Laboratory Biomarker Analysis OTHER

Correlative studies

Stage 1 (MV-NIS alone); Stage 2 (MV-NIS and cyclophosphamide)

Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter BIOLOGICAL

Given IV

Also known as: MV-NIS

Stage 1 (MV-NIS alone); Stage 2 (MV-NIS and cyclophosphamide)

Pharmacological Study OTHER

Correlative studies

Stage 1 (MV-NIS alone); Stage 2 (MV-NIS and cyclophosphamide)

Eligibility Criteria

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

You may qualify if:

• Myeloma relapsing from partial response or better
• Patients relapsing \> 18 months from transplant if not on maintenance, or
• If off maintenance, discontinued at least 6 months ago, or
• If relapsing on maintenance, at least 3 years from transplant, or
• Off prior myeloma therapy at least 6 months ago
• Sufficient tumor burden that is assessable for response
• Serum M-spike \>= 0.5 g/dL, or
• If immunoglobulin A (IgA) myeloma, IgA \> 1000 mg/dL, or
• Difference between involved and uninvolved free light chain (dFLC) \> 10 mg/dL, or
• Urine M-spike \>= 200 mg/24 hours, or
• Bone marrow plasmacytosis \>= 10%, or
• Plasmacytoma \>= 2 cm in diameter
• Absolute neutrophil count (ANC) \>= 1000/uL
• Platelets (PLT) \>= 50,000/uL
• Hemoglobin \>= 8.5 g/dl

You may not qualify if:

• Uncontrolled infection
• Active tuberculosis
• Any myeloma directed therapy within 12 weeks of registration including plasmapheresis or transfusion
• New York Heart Association classification III or IV, known symptomatic coronary artery disease, or symptoms of coronary artery disease on systems review
• Active central nervous system (CNS) disorder or seizure disorder
• Human immunodeficiency virus (HIV) positive test result
• Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (used for a non-Food and Drug Administration \[FDA\] approved indication and in the context of a research investigation)
• Previous exposure to heat inactivated measles virus vaccine (this vaccine was given to some individuals between the years of 1963-1967)
• Any of the following:
• Pregnant women or women of reproductive ability who are unwilling to use effective contraception
• Nursing women
• Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 4 weeks after stopping treatment
• Evidence of chronic or acute graft versus host disease or on-going treatment for graft versus host disease from prior allogeneic stem cell transplantation
• Exposure to household contacts =\< 15 months old or household contact with known immunodeficiency

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Cyclophosphamide

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)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Angela Dispenzieri, M.D., Morie A. Gertz, M.D.
• Organization: Mayo Clinic

Dispenzieri.Angela@mayo.edu, Gertz.Morie@mayo.edu

(507) 284-2511

Study Officials

• Angela Dispenzieri

  Mayo Clinic

  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: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2007
• First Posted: March 22, 2007
• Study Start: November 30, 2006
• Primary Completion: July 10, 2018
• Study Completion: November 20, 2019
• Last Updated: December 16, 2019
• Results First Posted: December 16, 2019

Record last verified: 2019-01

Locations

US (1)