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

NCT ID: NCT01670994

Last Updated: 2024-06-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-14
• Study Completion Date: 2015-09-09

Brief Summary

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.

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.

Conditions

Relapsed or Refractory Multiple Myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ALT-801 0.04mg/kg

Group Type: EXPERIMENTAL

ALT-801

Intervention Type: BIOLOGICAL

Intravenous infusion; 2 treatment cycles: on day 1, 3, 8, and 15 of each cycle

ALT-801 0.06mg/kg

Group Type: EXPERIMENTAL

ALT-801

Intervention Type: BIOLOGICAL

Intravenous infusion; 2 treatment cycles: on day 1, 3, 8, and 15 of each cycle

Interventions

ALT-801

Intravenous infusion; 2 treatment cycles: on day 1, 3, 8, and 15 of each cycle

Intervention Type: BIOLOGICAL

Other Intervention Names

c264scTCR-IL2

Eligibility Criteria

Exclusion Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Altor BioScience

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Iowa Hospitals

Iowa City, Iowa, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CA-ALT-801-01-11

Identifier Type: -

Identifier Source: org_study_id