Phase I Study of an Oncofetal Antigen Multi-Peptide Immunotherapy in Subjects With Hematologic Cancer

NCT02240537 | Unknown Phase 1

• 1 other identifier: BBMPI03-Hem-01
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 3

Brief Summary

The study is designed to evaluate safety, immunogenicity, and preliminary anti-tumor activity of a multi-peptide immunotherapy (BB-MPI-03) at three peptide+adjuvant dose levels. The peptides stimulate cytotoxic T-cells targeting oncofetal antigen (OFA). Subjects with AML, MM, sMM, or MDS who are off treatment and with stable disease or better, or who are not eligible for or refuse allogeneic HSCT are to be enrolled. The study will be conducted at 2 to 4 study centers in the US.

Conditions

Acute Myelogenous Leukemia (AML); Multiple Myeloma (MM); Myelodysplastic Syndrome (MDS); Smoldering Multiple Myeloma (sMM)

Keywords

AML; MM; MDS; sMM

Outcome Measures

Primary Outcomes (1)

• Determine the safety, dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and optimal biologic dose (OBD) of BB-MPI-03 and adjuvants in subjects with hematologic cancers who are off treatment and with stable disease (SD) or better.

  The safety and tolerability of BB-MPI-03 in Montanide emulsion preceded by sargramostim will be measured by: * The proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs), DLTs, and AEs leading to study vaccine discontinuation. * The proportion of subjects requiring a modification of the study treatment dose or schedule. * Change from baseline in absolute neutrophil counts (ANC) and platelet counts. * The proportion of subjects with local injection site reactivity. * Proportion of subjects experiencing infections or fevers requiring hospitalization and/or intravenous (IV) antibiotics.

  6 months treatment, 6 months follow-up

Secondary Outcomes (2)

• Determine the in vivo cellular immune response profile of BB-MPI-03 and adjuvants in subjects who receive 5 and 6 intradermal (ID) injections over a 6- month period.

  12 Months

• Evaluate any anti-tumor activity of BB-MPI-03 and adjuvants as assessed by disease reduction and lack of disease progression during and after treatment.

  12 Months

Study Arms (1)

Open Label Treatment Arm

EXPERIMENTAL

BB-MPI-03 peptides plus montanide plus sargramostim

Drug: Sargramostim; Drug: BB-MPI-03; Drug: Montanide

Interventions

Sargramostim DRUG

Drug: Sargramostim (GM-CSF) Other Names: Leukine Sargramostim (250 ug vial) is reconstituted with 0.5 ml of Sterile Water for Injection. Subjects will receive 0.5 ml intradermally (250 µg) near the arm pit or inside of thigh.

Also known as: Leukine

Open Label Treatment Arm

BB-MPI-03 DRUG

Other Names: Multi-peptide immunotherapy (MPI) is comprised of 3 cytotoxic T-cell epitopes derived from oncofetal antigen. There are 3 dose levels of study vaccine planned to be tested, starting at 0.25 mg each peptide (0.75 mg total peptide dose), then 0.5 mg of each peptide (1.5 mg total) and finally 1 mg each peptide (3 mg total). At the starting dose of 0.75 mg, the BB MPI 03-15 mg vial is used and 100 ul is administered; at the 1.5 mg dose, 200 ul of the BB MPI 03-15 mg vial is used; at the 3 mg dose, 200 ul of the BB MPI 03-30 mg is used.

Also known as: Multi-peptide Immunotherapy

Open Label Treatment Arm

Montanide DRUG

Drug: Montanide Other Names: mineral oil, USP BB-MPI-03 is emulsified with Montanide and administered intradermally (ID) within 1-2 cm of the 2 sargramostim injection sites 1-3 minutes after sargramostim administration. Subjects and the injection sites are to be monitored for 1 hour after sargramostim and BB-MPI-03 emulsion administration.

Also known as: Emulsion

Open Label Treatment Arm

Eligibility Criteria

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

You may qualify if:

• a. History of morphologically confirmed AML w/ classification other than WHO Acute Promyelocytic Leukemia (FAB M3), based on bone marrow examination.
• i. not a candidate for allogeneic HSCT or no intention to move to HSCT at time of enrollment.
• ii. Patient's AML could be in morphologic CR or no further cytotoxic chemotherapy is currently being considered.
• iii. Completed consolidation chemotherapy, if available and/or appropriate for patient.
• iv. Can have history of allogeneic HSCT transplant, but must be off immunosuppression for at least 2 wks. before enrollment and w/o GVHD and/or toxicities from HSCT.
• b. Diagnosed in past 5 years w/ smoldering MM at high risk of progressing to symptomatic MM.
• i. Diagnosis defined as: Bone marrow infiltration with plasma cells (PCs) ≥10% and presence of a monoclonal component, Ig G ≥3 g/dl or IgA ≥2 g/dl or Bence-Jones proteinuria \>1 g/dl and absence of lytic lesions on skeletal survey, absence of hypercalcemia (corrected calcium \<11 mg/dl), absence of renal failure (creatinine ≤1.5 x ULN), and absence of anemia (hemoglobin \>10 g/dl or not 2 g/dl below LLN).
• ii. Must meet one of following:
• ≥10% PCs in bone marrow and IgG ≥3 g/dl or IgA ≥2 g/dl,
• ≥10% PCs in bone marrow and serum FLC ratio (involved : uninvolved) \>100 in blood, or
• IgG ≥3 g/dl or IgA ≥2 g/dl and FLC ratio (involved: uninvolved) \>100 in blood. c. MM post-treatment disease that is clinically stable and does not require treatment at least 4 weeks prior to enrollment.
• i. At least one line of treatment and achieved at least PR by IMWG ii. Stable disease or better per IMWG based on 2 subsequent assessments at least one month apart d. history of morphologically confirmed MDS i. previously received at least one treatment for MDS, including but not limited to chemotherapy or hypomethylating agent(s). Subjects may be previously untreated if they refuse treatment with or are not appropriate candidates for chemotherapy or hypomethylating agent(s) in the investigator's opinion.
• ii. intermediate, high, or very high risk MDS by IPSS-r iii. No curative intent option of allogeneic HSCT or refused consideration for allogeneic HSCT iv. Could have history of allogeneic HSCT transplant and relapsed, but must be off immunosuppression for at least 2 weeks before enrollment and without GVHD and/or toxicities from HSCT.
• \. Low, moderate, to high levels of OFA expression by IHC analysis of tumor specimens.
• \. HLA-A\*02 haplotype.

You may not qualify if:

• Received chemotherapy, biological therapy, or radiation therapy less than one month before D1
• No prior history of active CNS involvement
• Grade 2 or higher peripheral neuropathy w/in 28 days
• Acute promyelocytic leukemia (FAB M3)
• Other active systemic malignancy treated w/ cytotoxic chemotherapy in previous 12 mos.
• Monoclonal gammopathy of undetermined significance
• For smoldering MM, baseline bone lesions or plasmacytomas
• For smoldering MM, lytic lesions on skeletal surveys and hypercalcemia (i.e., ≥11 mg/dL)
• Known HIV or hepatitis virus infection
• Active infection requiring antibiotics
• History of prior or active autoimmune disease such as Lupus or rheumatoid arthritis
• Significant kidney or liver disease, uncontrolled severe cardiovascular or pulmonary disease, other uncontrolled medical condition that would compromise subject's ability to tolerate study treatment
• Received any investigational treatment w/in 30 days
• Receiving systemic glucocorticosteroid \>10 mg daily. Concurrent use after registration on study should be restricted to equivalent of prednisone 10 mg per day. Prior or concurrent topical or localized glucocorticosteroid therapy to treat non-malignant comorbid disorders is permitted. Subject requiring routine use of steroid inhalers are not eligible.
• Major surgery w/in 4 wks.

Sponsors & Collaborators

• Benovus Bio, Inc.: lead

Study Sites (3)

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Multiple Myeloma; Myelodysplastic Syndromes; Smoldering Multiple Myeloma

Interventions

sargramostim; Monatide (IMS 3015); Emulsions

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Precancerous Conditions; Hypergammaglobulinemia

Intervention Hierarchy (Ancestors)

Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2014
• First Posted: September 15, 2014
• Study Start: January 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: June 1, 2017
• Last Updated: April 19, 2016

Record last verified: 2016-04

Locations

US (3)