Therapy for Progressive and/or Refractory Hematologic Malignancies

NCT02223312 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: KiroVAX002.2BSK01 Dendritic cell vaccine
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the safety and effectiveness of Tumor Associated Peptide Antigen (TAPA) pulsed dendritic cell (DC) vaccines in the treatment of progressive and/or refractory hematologic malignancies (HM). We hypothesize that treatment of patients with relapsed and/or refractory HM, without available potentially curative treatment options, and whose neoplastic cells express at least one (1) TAPA of a defined panel of TAPAs, using low-dose cyclophosphamide (CYP) followed by an autologous, monocyte-derived, TAPA-pulsed DC vaccine and low-dose granulocyte macrophage colony stimulating factor (GM-CSF), will result in TAPA-specific T-cell responses without significant toxicities. We also hypothesize CD4+ T-cell and CD8+ T-cell responses generated against specific TAPAs may translate into clinical antitumor activity.

Conditions

Cancer; Hematologic Malignancies

Outcome Measures

Primary Outcomes (1)

• Number of adverse events that occur due to toxicity of low-dose CYP followed by TAPA-pulsed DC therapy and low-dose GM-CSF administration

  Every 7 days

Secondary Outcomes (2)

• Immunological efficacy as indicated by T-cell cytokine levels

  up to 5 months

• Immunological efficacy as determined by a positive delayed type hypersensitivity (DTH) skin test

  up to 5 months

Study Arms (1)

TAPA-pulsed DC vaccine

EXPERIMENTAL

The subject will take low-dose cyclophosphamide by mouth for 5 days starting 7 days prior to the vaccine cycle. The vaccine contains 1 x 10\^7 TAPA-pulsed dendritic cells and is administered SQ with low-dose GM-CSF following the low-dose cyclophosphamide cycle. A total of six (6) cycles of cyclophosphamide and six (6) DC vaccines cycles will be administered alternating every 14 days.

Biological: TAPA-pulsed DC vaccine

Interventions

TAPA-pulsed DC vaccine BIOLOGICAL

A cycle of low-dose cyclophosphamide (100mg/day) by mouth for 5 days starting seven 7 days prior to the DC vaccine cycle to reduce Treg activity. Low-dose cyclophosphamide will be taken every 14 days for six 6 cycles. A total of 6 vaccines containing 1 x 10\^7 TAPA-pulsed DC will be administered SQ every 14 days. The DC vaccine is given on Day 1 of the DCV cycle plus low-dose GM-CSF 50mcg/day SQ x 5 days (Day 1 to Day 4). GM-CSF is administered for 5 days to increase monocyte production and dendritic cell precursors to optimize immune responses.

TAPA-pulsed DC vaccine

Eligibility Criteria

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

You may qualify if:

• Ability to provide informed consent.
• Patients at least eighteen (18) years of age diagnosed with the following histologically proven, progressive and/or refractory HM following standard therapy: Multiple Myeloma (MM), Hodgkins Disease (HD), Non-Hodgkins Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL), and without potentially curative therapeutic options, will be eligible.
• Expression of one (1) or more of the following TAPAs: SP17, AKAP4, Ropporin, PTTG1 and Span-xb, by either RT-PCR and/or immunocytochemistry, Western blotting or ELISA, in neoplastic cells and/or blood.
• Presence of measurable or evaluable disease.
• Patients must not have any active infectious process.
• Patients must have a negative test for HIV, Hepatitis A, B, and C.
• Patients must not be receiving active immunosuppressive therapy.
• Patients must have discontinued systemic antineoplastic therapy (including systemic corticosteroids) at least four (4) weeks prior to enrollment.
• Patients may not have any known allergy to GM-CSF.
• Patients must be willing to provide at least 250 mL, and up to 500 mL, of whole blood obtained by phlebotomy and/or consent to leukapheresis for DC generation.
• Adequate renal and hepatic function (creatinine ≤ 2.0 mg/dl, bilirubin ≤ 2.0 mg/dl, AST and ALT ≤ 4X upper limit of normal range).
• Adequate hematologic function (Platelets ≥ 60,000/mm3, lymphocytes ≥ 1,000/mm3, neutrophils ≥ 750/mm3, hemoglobin ≥ 10 g/dl).
• Karnofsky performance status ≥ 70%.
• Expected survival ≥ 6 months.
• Patient Human Leucocyte Antigen (HLA) typing should demonstrate HLA-A\*01, and/or HLA-A-\*02, and/or HLA-A\*24 restriction.

You may not qualify if:

• Patients without confirmed progressive and/or refractory MM, HD, NHL and CLL, or those with confirmed progressive and/or refractory MM, HD, NHL and CLL but who have a potentially curative therapeutic intervention available, are excluded from the study.
• Patients without measurable or evaluable disease.
• Patients receiving cytotoxic therapy, radiation therapy, immunotherapy or non-topical steroids for HM within four (4) weeks of enrollment.
• Active immunosuppressive or cytotoxic therapy (excluding topical steroids) for any other condition.
• Persistent fever (\>24 hours) documented by repeated measurement or active, uncontrolled infection within 4 weeks of enrollment.
• Active ischemic heart disease or history of myocardial infarction within six months.
• Active autoimmune disease, including, but not limited to, Systemic Lupus Erythematosus (SLE), Multiple Sclerosis (MS), Ankylosing Spondylitis (AS), and Rheumatoid Arthritis (RA).
• Pregnancy or breast feeding.
• Active second invasive malignancy, other than basal cell carcinoma of the skin.
• Life expectancy of less than 6 months.
• Patients with contraindications to CYP and/or GM-CSF.
• Patients who have received organ transplantations.
• Patients with psychological or geographic conditions that prevent adequate follow-up or compliance with the study protocol.
• Patients with documented primary or secondary central nervous system (CNS) involvement at any time during disease course are excluded from the study.
• Patient with HLA-A alleles not belonging to any of the following subtypes: HLA-A\*01, or HLA-A\*02, or HLA-A\*24.

Sponsors & Collaborators

• Kiromic BioPharma Inc.: lead

MeSH Terms

Conditions

Neoplasms; Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Hematologic Diseases; Hemic and Lymphatic Diseases

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: August 11, 2014
• First Posted: August 22, 2014
• Study Start: July 28, 2017
• Primary Completion: October 31, 2018
• Study Completion: January 31, 2019
• Last Updated: August 28, 2018

Record last verified: 2018-01