QUILT-3.020: A Study of ALT-801 in Patients With Relapsed or Refractory Multiple Myeloma

A Study of ALT-801 in Patients With Relapsed or Refractory Multiple Myeloma

This is a Phase Ib/II, open-label, multi-center and competitive enrollment study of ALT-801 in patients who have relapsed or refractory multiple myeloma.

Study Overview

• Status: Terminated
• Conditions: Relapsed or Refractory Multiple Myeloma
• Intervention / Treatment: Biological: ALT-801

Detailed Description

Multiple Myeloma (MM) is a plasma cell malignancy that makes up 1% of all cancers and 10% of hematologic neoplasma, and is the second most commonly diagnosed hematologic malignancy. There are an estimated 20,520 new cases of MM and 10,610 deaths due to MM in the United States. Historically, standard first-line therapy for MM consisted of combination therapy with an alkylating agent, such as melphalan and prednisone. Response rates with such combination therapy are approximately 50%, but five-year survival rates remain low at 33%. For younger patients, debulking chemotherapy followed by autologous stem cell transplant (ASCT) with melphalan is the treatment of choice to increase the potential for a sustained durable remission. However, a large percentage of patients diagnosed with MM are not suitable candidates for ASCT because of age or comorbidities. The approach to MM treatment has undergone a radical transformation over the past decade with the introduction of the proteasome inhibitor, bortezomib, and immunomodulatory drugs (ImiDs), thalidomide or lenalidomide. Despite some advances in the treatment of MM, the disease remains incurable due to the persistence of minimal residual disease. Thus, novel modalities complementing or improving current treatment options are needed.

There is ample evidence that immunomodulatory drugs are effective against myeloma. Lenalidomide and thalidomide have been shown to stimulate T cells in the presence of antigen presenting cells via costimulatory pathway. Also, modulation of NK cell function has been associated with anti-tumor activity observed in MM patients treated with lenalidomide. It has been demonstrated that NK cells exhibit potent anti-MM activity following IL-2 administration, and ex vivo IL-2-activated and intravenously administered NK cells prolong survival in MM-bearing mice. Thus further demonstrating the role and importance of NK cells in the treatment of MM. Taken together, these data suggest that the use of a potent immunotherapeutic is an attractive approach to provide durable immune responses to or even potentially curing patients with MM.

Additionally, immunotherapy is a well-established approach for treating other cancer types. One strategy that has received attention is treatment with cytokines such as IL-2 to enhance anti-tumor immunity. Unfortunately, the considerable toxicity associated with this treatment makes it difficult to achieve an effective dose at the site of the tumor and limits the population that can be treated. Thus, there is a critical need for innovative strategies that enhance the effects of IL-2, reduce its toxicity without compromising clinical benefit, provide a more convenient dosing regimen, and treat other diagnoses including MM.

Altor Bioscience Corp. has developed a tumor-targeted IL-2 fusion protein, ALT-801, comprising human recombinant IL-2 genetically linked to a TCR domain capable of binding a tumor associated human p53 peptide presented in the context of HLA-A2.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

ENTRY CRITERIA:

DISEASE CHARATERISTICS:

• Confirmed diagnosis of relapsed/refractory multiple myeloma after treatment with at least two different previous regimens.

  • Refractory disease is defined as progressive disease while on therapy or progression within 60 days of therapy.
  • Progressive disease is defined by a 25% increase from the lowest response value in specified tests.

• Measurable disease as defined by at least one of the following:

  • Serum M-protein ≥ 1g/dL (for IgG, IgM) or 0.5 g/dL (for IgA)
  • Urine M-protein ≥ 200mg/24hours
  • Serum free light chains ≥ 10 mg/dL and abnormal kappa/lambda ratio

PRIOR/CONCURRENT THERAPY:

• No anti-myeloma treatments within 28 days before the start of study treatment.
• Must have recovered from side effects of prior treatments.

PATIENT CHARACTERISTICS:

Age

• ≥ 18 years

Performance Status

• ECOG 0, 1, or 2

Bone Marrow Reserve

• Absolute neutrophil count (AGC/ANC) ≥ 1,000/uL
• Platelets ≥ 30,000/uL
• Hemoglobin ≥ 8g/dL

Renal Function

• Glomerular Filtration Rate (GFR) > 45mL/min/1.73m^2

Hepatic Function

• Total bilirubin ≤ 2.0 X ULN
• AST, ALT, ALP ≤ 3.0 X ULN, or ≤ 5.0 X ULN (if liver metastases exist)

Cardiovascular

• No congestive heart failure < 6 months
• No unstable angina pectoris < 6 months
• No myocardial infarction < 6 months
• No history of ventricular arrhythmias
• No history of supraventricular arrhythmias
• No NYHA Class > II CHF
• Normal Transthoracic Echocardiogram (TTE) is required for patients with history of EKG abnormalities, CHF, coronary artery disease or other cardiac disease, or with a history of having received adriamycin or doxorubicin
• Patients with a left ventricular ejection fraction (LVEF) of less than 50% will be excluded from study entry

Pulmonary

• Normal clinical assessment of pulmonary function

Other

• Negative serum pregnancy test if female and of childbearing potential
• Women who are not pregnant or nursing
• Subjects, both females and males, with reproductive potential must agree to use effective contraceptive measures for the duration of the study
• No known autoimmune disease other than corrected hypothyroidism
• No known prior organ allograft or allogeneic transplantation
• Not HIV positive
• No history or evidence of uncontrollable CNS disease
• No psychiatric illness/social situation
• No other illness that in the opinion of the investigator would exclude the subject from participating in the study
• Must provide informed consent and HIPPA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations
• Active systemic infection requiring parenteral antibiotic therapy.
• No ongoing chronic systemic steroid therapy required.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALT-801 0.04mg/kg	Biological: ALT-801; Intravenous infusion; 2 treatment cycles: on day 1, 3, 8, and 15 of each cycle; Other Names: c264scTCR-IL2
Experimental: ALT-801 0.06mg/kg	Biological: ALT-801; Intravenous infusion; 2 treatment cycles: on day 1, 3, 8, and 15 of each cycle; Other Names: c264scTCR-IL2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Related Adverse Events	Number of treatment related AEs that occur or worsen after the first dose of study treatment	7 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Benefit	For phase Ib and II Number of participants with an objective response, which includes, a complete response, a partial response or a stable disease	12 weeks
Immunogenicity and Pharmacokinetics	For phase Ib and II Measures the anti-ALT-801 and IL-2 neutralizing effects Area under the plasma concentration-time curve from time zero to infinity (AUC) and the half-life of ALT-801	8 weeks
Tumor Typing	For phase Ib and II To assess the relationship between tumor presentation of HLA-A*0201/p53 aa 264-272 complex and the safety, immune response and clinical benefit of study treatment	1 month
Overall and progression-free survival	For phase Ib and II All enrolled patients will be assessed every 3 months during year 1 and then every 6 months during years 2 and 3 from the start of study treatment to determine their overall and progression-free survival	3 years
Duration of Response	All enrolled patients will be assessed every 3 months during year 1 and then every 6 months during years 2 and 3 from the start of study treatment to determine their duration of response	up to 3 years

Collaborators and Investigators

• Sponsor: Altor BioScience
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Hing C Wong, PhD, Altor BioScience

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2012
• Primary Completion (Actual): September 9, 2015
• Study Completion (Actual): September 9, 2015

Study Registration Dates

• First Submitted: August 20, 2012
• First Submitted That Met QC Criteria: August 20, 2012
• First Posted (Estimated): August 23, 2012

Study Record Updates

• Last Update Posted (Actual): June 18, 2024
• Last Update Submitted That Met QC Criteria: May 24, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: immunotherapy; cancer; immunochemotherapy; targeted; metastatic; interleukin-2; antitumor; TCR; T-cell receptor; p53; p53 gene; p53 tumor supressor protein; HLA-A2 positive; HLA-A*0201/p53 aa264-272; HLA complex; relapsed; refractory; multiple myeloma; IFN-γ and TNF-α
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: CA-ALT-801-01-11

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO