Clinical Trial: Blinatumomab and Nivolumab With or Without Ipilimumab in Treating Patients With Poor-Risk Relapsed or Refractory CD19+ Precursor B-Lymphoblastic Leukemia

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase 1 Study of Blinatumomab in Combination With Checkpoint Inhibitor(s) of PD-1 (Nivolumab) or Both PD-1 (Nivolumab) and CTLA-4 (Ipilimumab) in Patients With Poor-Risk, Relapsed or Refractory CD19

Brief Summary: This phase I trial studies the side effects and best dose of blinatumomab when given with nivolumab alone or nivolumab and ipilimumab in treating patients with poor-risk CD19+ precursor B-lymphoblastic leukemia that has come back after a period of improvement or has not responded to treatment. Monoclonal antibodies, such as blinatumomab, nivolumab and ipilimumab, may interfere with the ability of tumor cells to grow and spread.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To evaluate the safety and tolerability of the blinatumomab given in combination with nivolumab alone, or in combination with both nivolumab and ipilimumab in subjects with poor-risk, relapsed or refractory CD19+ pre-B cell ALL or CD19+ mixed phenotype acute leukemia (MPAL).

II. To determine the maximum tolerated dose (MTD) of the combination of blinatumomab plus nivolumab, and blinatumomab plus both nivolumab and ipilimumab and to further confirm the safety of the combination therapy in subjects with poor-risk, relapsed or refractory CD19+ pre-B cell acute lymphoblastic leukemia (ALL) or CD19+ mixed phenotype acute leukemia (MPAL).

SECONDARY OBJECTIVES:

I. To observe and record anti-leukemia activity of blinatumomab and nivolumab, and blinatumomab plus both nivolumab and ipilimumab, including the effects on minimal residual disease (MRD).

II. To assess preliminary anti-leukemia activity in an expansion cohort of patients with poor-risk, relapsed or refractory CD19+ precursor B-lymphoblastic leukemia, or CD19+ mixed phenotype acute leukemia (MPAL).

TERTIARY OBJECTIVES:

I. To examine changes in absolute lymphocyte count and distribution of T cell subsets (CD4+, CD8+, regulatory T cells [Tregs], effector T cells [Teffs]) and their differentiation status, natural killer (NK) cells, and B cells before and post-blinatumomab, and immune checkpoint inhibitor(s) therapy in both peripheral blood and the bone marrow microenvironment.

II. To explore changes in T cell co-signaling receptors expression in defined T cel
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Incidence of adverse events as graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 2 years ]
    All adverse events and toxicities will be tabulated and reported by type and grade for all dose levels of all treatment combinations and the proportions reported with exact 95% binomial confidence intervals.
  • Maximum tolerated dose defined as the maximum dose level in the absence of dose limiting toxicity in each patient assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 2 years ]
    The maximum tolerated dose of the combination of blinatumomab plus nivolumab, and blinatumomab plus both nivolumab and ipilimumab will be determined in subjects with poor-risk, relapsed or refractory CD19+ Pre-B cell acute lymphoblastic leukemia or CD19+ mixed phenotype acute leukemia.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Anti-leukemia activity [ Time Frame: Up to 2 years ]
    Anti-leukemia activity will be assessed.
  • Complete remission [ Time Frame: Up to 2 years ]
    The frequency distribution of responses, including complete remission, complete remission with incomplete blood count recovery or progressive disease will be reported by treatment arm and dose level for all patients on study and reported with exact 95% confidence intervals.
  • Complete remission with incomplete blood count recovery [ Time Frame: Up to 2 years ]
    The frequency distribution of responses, including complete remission, complete remission with incomplete blood count recovery or progressive disease will be reported by treatment arm and dose level for all patients on study and reported with exact 95% confidence intervals.
  • Duration of response [ Time Frame: Time from measured response to progressive disease, death, or study end, assessed up to 2 years ]
    Will be analyzed using the Kaplan Meier method. A sensitivity analysis may be performed to evaluate duration of response while excluding patients who go on to have an allogeneic-hematopoietic stem cell transplantation.
  • Minimal residual disease assessed by flow cytometry [ Time Frame: Up to 2 years ]
    For patients who have a clinical response, the frequency of minmal residual disease positive versus minimal residual disease negative responses will be reported by treatment arm and dose level for all patients on study.
  • Overall survival [ Time Frame: From the first day of treatment on the study until death or last known follow up, assessed up to 2 years ]
    Will be measured using the Kaplan Meier method.
  • Progressive disease [ Time Frame: Up to 2 years ]
    The frequency distribution of responses, including complete remission, complete remission with incomplete blood count recovery or progressive disease will be reported by treatment arm and dose level for all patients on study and reported with exact 95% confidence intervals.


Original Secondary Outcome: Same as current

Information By: National Cancer Institute (NCI)

Dates:
Date Received: August 23, 2016
Date Started: May 25, 2017
Date Completion: November 5, 2021
Last Updated: May 24, 2017
Last Verified: May 2017