Blinatumomab and Pembrolizumab for Adults With Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia With High Marrow Lymphoblasts

• Status: Recruiting
• Trial end date: 2023-08-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase I/II study of blinatumomab in combination with pembrolizumab in adult patients with relapsed or refractory B-lineage ALL The primary objective of this study is to determine if the addition of pembrolizumab to blinatumomab improves the overall response rate (CR+ CRh) relative to blinatumomab alone in adult subjects with relapsed or refractory B-cell acute lymphoblastic leukemia with high bone marrow lymphoblast percentage (>50% lymphoblasts).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Matthew Wieduwilt, M.D., Ph.D.
• Collaborators: Amgen; Merck Sharp & Dohme Corp.
• Treatments: Antibodies, Bispecific; Blinatumomab; Pembrolizumab

Criteria

Inclusion Criteria:

• Relapsed or refractory B-lineage acute lymphoblastic leukemia having received at least 1 prior line of therapy

• Philadelphia chromosome/BCR-ABL1-positive B-lineage ALL must have failed at least 1 second or third generation tyrosine kinase inhibitor (TKI) or be intolerant to TKIs

• Greater than 50% lymphoblasts on screening bone marrow aspirate or biopsy

• Adequate organ function

• Women of child-bearing potential and men with partners of child-bearing potential must agree to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication.

• A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

• Has not undergone a hysterectomy or bilateral oophorectomy; or

• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)

• Male subjects must agree to use a latex condom during sexual contact with females of childbearing potential even if they have had a successful vasectomy starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Exclusion Criteria:

• Allogeneic hematopoietic cell transplantation within 5 years of study drug administration

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.

• GM-CSF or G-CSF use within 2 weeks of study treatment and throughout the study

• Prior checkpoint inhibitor therapy including anti-PD1, anti-PD-L1, anti-CTLA4, anti- CD137, or anti-PD-L2 therapy

• Active CNS or testicular involvement by leukemia

• History of neurologic disorder

• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.

• Burkitt lymphoma/leukemia

• Has a diagnosis of congenital immunodeficiency

• Has a known history of active TB (Bacillus Tuberculosis)

• Known HIV infection

• Active hepatitis B or hepatitis C infection

• Has received a live vaccine within 30 days prior to first dose

• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.

• History of autoimmune disease

• Known interstitial lung disease

• Any evidence of active, non-infectious pneumonitis or has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis

• Patients who have received chemotherapy or radiotherapy within 2 weeks prior to entering the study or has not recovered from adverse events due to agents administered more than 2 weeks earlier.

• Patients who are less than 4 weeks from surgery or have insufficient recovery from surgical-related trauma or wound healing.

• Known impaired cardiac function