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Leukemia, B-cellPhase 1NCT03605589

Pembro + Blina Combination in Pediatric and Young Adult Patients With Relapsed/Refractory Acute Leukemia or Lymphoma

A Phase 1 study testing Blinatumomab and Pembrolizumab in people with Leukemia, B-cell and Lymphoma, B-Cell, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This study combines the immune checkpoint inhibitor pembrolizumab with the BITE antibody blinatumomab for the treatment of relapsed/refractory pre-B cell ALL. Pembrolizumab at the proposed dosing schedule has been very well tolerated in adult studies, including elderly and unfit patients, as well as in pediatric… Read more about this study

Who is it for?
Ages 1 year to 40 years
Conditions the study is for
Leukemia, B-cell, Lymphoma, B-Cell
What is being tested?
Blinatumomab and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
27 Sep 2018to Jan 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 40 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Age 1-40
  • Diagnosis of CD19 positive B-cell acute lymphoblastic leukemia (ALL) positive B-cell acute lymphoblastic leukemia (ALL) or CD19 positive B-cell lymphoma
  • Patients with CD19 positive B-ALL must have greater than or equal to 5% lymphoblast in the bone marrow AND meet one of the following criteria:
  • 2nd or greater relapse
  • Any relapse after allo-HSCT
  • Refractory disease
Show all 13Show fewer
  • Patients with CD19 positive relapsed/refractory lymphoma must be in 2nd or greater relapse or have refractory disease with the markers of disease burden
  • Patients with CNS 1 or CNS 2 leukemia are eligible.Patients with CNS 3 leukemia are not eligible. However, patients with a history of CNS 3 status who have been sufficiently treated are eligible if currently CNS 1 or 2. Patients with an isolated CNS relapse are not eligible.
  • Karnofsky performance level greater than or equal to 50 % for patients older than 16
  • Lansky performance level greater than or equal to 50 % less than or equal to 16
  • Patients recovered from acute toxicities from prior anti-cancer chemotherapy including HSCT, cytotoxic therapy, prior blinatumomab, biologic, immunotherapy, monoclonal antibody, XRT and corticosteroid therapy
  • Patients with adequate hematological, renal, liver, cardiac, pulmonary and CNS organ functions
  • Female participants of child bearing age must have negative pregnancy test, abstain or use contraception for 120 days after last dose of pembrolizumab

Who cannot join

  • Patients with the following diagnoses: CNS 3 leukemia, CNS lymphoma, active GVHD, Downs Syndrome, CNS or testicular relapse, optic nerve or retinal involvement requiring radiation therapy
  • Pregnant or breastfeeding
  • Concomitant corticosteroids, immunosuppressive therapies, investigational drugs, anti-cancer agents
  • Concurrent illnesses including: history of any grade autoimmune disorder, Grade 2 or higher hypothyroidism die to autoimmunity, uncontrolled infection, interstitial lung disease or pneumonitis
  • Patients with other concurrent malignancies
  • Patients who have received live vaccines within the last 30 days
  • Patients with history of solid organ transplant

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

Other trials in United States

About this study

Official title: A Pilot Study of Blinatumomab in Combination With a PD1 Inhibitor, Pembrolizumab, in Pediatric and Young Adult Patients With Relapsed/Refractory CD19 Positive B-cell Acute Leukemia or Lymphoma

This study combines the immune checkpoint inhibitor pembrolizumab with the BITE antibody blinatumomab for the treatment of relapsed/refractory pre-B cell ALL. Pembrolizumab at the proposed dosing schedule has been very well tolerated in adult studies, including elderly and unfit patients, as well as in pediatric patients. Both blinatumomab and pembrolizumab are FDA-approved for use in children as well as adults. Phase I/II trials in adult patients have demonstrated safety and activity of pembrolizumab in combination with multiple agents. In this trial, the combination of pembrolizumab and blinatumomab will be investigated for toxicity as well as possible synergy in the treatment of relapsed/refractory pre-B cell ALL.

This is a single institution investigator-initiated pilot study designed to test the safety and feasibility of combining pembrolizumab and blinatumomab immunotherapies in children, adolescents, and young adults with CD19 positive hematologic malignancies. The investigator will define the toxicity profile of the combination in two safety strata based on whether or not a patient has had a prior allogeneic hematopoietic stem cell transplant (HSCT), as they hypothesize that the immune toxicities may differ between strata. In addition, the overall response rate (CR/CRh) to this therapy will be estimated. Additional biologic correlates will be conducted to delineate the effect of the combination therapy on the patient's leukemia/lymphoma and T-cell populations and how this may influence response to therapy.

Read the detailed description

Participants who meet study eligibility will receive or continue to receive blinatumomab by continuous IV infusion for 28 days and also receive pembrolizumab (by IV infusion over 30 minutes) on day 12 of cycle 1 and day 5 of cycle 2.

One cycle lasts 35 days and patients will receive 2 cycles of therapy.

Being tested
Blinatumomab, Pembrolizumab
Keywords
Blinatumomab, Pembrolizumab, CD19 positive, Relapsed, Refractory
Medical subject headings
Leukemia, B-Cell, Lymphoma, B-Cell, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BlinatumomabDrug

    Also called Blincyto

    Continuous IV infusion

  • PembrolizumabDrug

    Also called Keytruda

    IV infusion

Study groups in NCT03605589
Study groupRoleWhat they receive
Blinatumomab and PembrolizumabExperimentalBlinatumomab and Pembrolizumab will be given for 2 cycles (each cycle lasts 35 days). Blinatumomab administered as a continuous IV infusion. Patient Weight Greater Than or Equal to 45 kg (Fixed dose) Patient Weight Less Than 45 kg (BSA-based dose) Cycle 1 (Days 1-7): Patient Weight Greater Than or Equal to 45 kg: 9 mcg/day Patient Weight Less Than 45 kg: 5 mcg/m2/day Cycle 1(Days 8-28): Patient Weight Greater Than or Equal to 45 kg: 28 mcg/day Patient Weight Less Than 45 kg: 15 mcg/m2/day Cycle 2 (Days 1-28): Patient Weight Greater Than or Equal to 45 kg: 28 mcg/day Patient Weight Less Than 45 kg: 15 mcg/m2/day Pembrolizumab: 2 mg/kg (max dose 200 mg) administered as a 30 minute IV infusion on day 12 of cycle 1 and day 5 of cycle 2.
Receives: Drug: Blinatumomab; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Feasibility of combining pembrolizumab and blinatumomab (dose limiting toxicities)

    Number of DLTs

    Measured: 2 cycles of therapy (70 days)

  2. Treatment related toxicities

    Number of related adverse events

    Measured: 2 cycles of therapy (70 days)

Secondary outcomes (1)

  1. Disease response

    Estimate of overall response rate (CR/CRh)

    Measured: 2 cycles (70 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jul 2018
  2. Study start27 Sep 2018
  3. Primary completionAug 2021 (estimated)
  4. Study completionJan 2022 (estimated)

Why it stopped: Lack of enrollment due to the availability of other novel salvage therapies for relapsed/refractory B-ALL.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
This is a pilot study to assess the safety, tolerability, and preliminary anti-tumor activity of the combination of pembrolizumab and blinatumomab in children and young adult patients with relapsed and/or refractory CD19 positive B-cell hematologic malignancies.
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03605589
Sponsor's protocol ID
Pembro-EB-1701
Status last verified
Mar 2021
First submitted
20 Jul 2018
Last updated
1 Apr 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Escherich G, Horstmann MA, Zimmermann M, Janka-Schaub GE; COALL study group. Cooperative study group for childhood acute lymphoblastic leukaemia (COALL): long-term results of trials 82,85,89,92 and 97. Leukemia. 2010 Feb;24(2):298-308. doi: 10.1038/leu.2009.249. Epub 2009 Dec 17.

    PubMed 20016530

  • Moricke A, Zimmermann M, Reiter A, Henze G, Schrauder A, Gadner H, Ludwig WD, Ritter J, Harbott J, Mann G, Klingebiel T, Zintl F, Niemeyer C, Kremens B, Niggli F, Niethammer D, Welte K, Stanulla M, Odenwald E, Riehm H, Schrappe M. Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000. Leukemia. 2010 Feb;24(2):265-84. doi: 10.1038/leu.2009.257. Epub 2009 Dec 10.

    PubMed 20010625

  • Schmiegelow K, Forestier E, Hellebostad M, Heyman M, Kristinsson J, Soderhall S, Taskinen M; Nordic Society of Paediatric Haematology and Oncology. Long-term results of NOPHO ALL-92 and ALL-2000 studies of childhood acute lymphoblastic leukemia. Leukemia. 2010 Feb;24(2):345-54. doi: 10.1038/leu.2009.251. Epub 2009 Dec 10.

    PubMed 20010622

  • Stary J, Zimmermann M, Campbell M, Castillo L, Dibar E, Donska S, Gonzalez A, Izraeli S, Janic D, Jazbec J, Konja J, Kaiserova E, Kowalczyk J, Kovacs G, Li CK, Magyarosy E, Popa A, Stark B, Jabali Y, Trka J, Hrusak O, Riehm H, Masera G, Schrappe M. Intensive chemotherapy for childhood acute lymphoblastic leukemia: results of the randomized intercontinental trial ALL IC-BFM 2002. J Clin Oncol. 2014 Jan 20;32(3):174-84. doi: 10.1200/JCO.2013.48.6522. Epub 2013 Dec 16.

    PubMed 24344215

  • Gaynon PS. Childhood acute lymphoblastic leukaemia and relapse. Br J Haematol. 2005 Dec;131(5):579-87. doi: 10.1111/j.1365-2141.2005.05773.x.

    PubMed 16351633

  • Raetz EA, Bhatla T. Where do we stand in the treatment of relapsed acute lymphoblastic leukemia? Hematology Am Soc Hematol Educ Program. 2012;2012:129-36. doi: 10.1182/asheducation-2012.1.129.

    PubMed 23233571

  • Tallen G, Ratei R, Mann G, Kaspers G, Niggli F, Karachunsky A, Ebell W, Escherich G, Schrappe M, Klingebiel T, Fengler R, Henze G, von Stackelberg A. Long-term outcome in children with relapsed acute lymphoblastic leukemia after time-point and site-of-relapse stratification and intensified short-course multidrug chemotherapy: results of trial ALL-REZ BFM 90. J Clin Oncol. 2010 May 10;28(14):2339-47. doi: 10.1200/JCO.2009.25.1983. Epub 2010 Apr 12.

    PubMed 20385996

  • Zhu M, Wu B, Brandl C, Johnson J, Wolf A, Chow A, Doshi S. Blinatumomab, a Bispecific T-cell Engager (BiTE((R))) for CD-19 Targeted Cancer Immunotherapy: Clinical Pharmacology and Its Implications. Clin Pharmacokinet. 2016 Oct;55(10):1271-1288. doi: 10.1007/s40262-016-0405-4.

    PubMed 27209293

  • von Stackelberg A, Locatelli F, Zugmaier G, Handgretinger R, Trippett TM, Rizzari C, Bader P, O'Brien MM, Brethon B, Bhojwani D, Schlegel PG, Borkhardt A, Rheingold SR, Cooper TM, Zwaan CM, Barnette P, Messina C, Michel G, DuBois SG, Hu K, Zhu M, Whitlock JA, Gore L. Phase I/Phase II Study of Blinatumomab in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia. J Clin Oncol. 2016 Dec 20;34(36):4381-4389. doi: 10.1200/JCO.2016.67.3301. Epub 2016 Oct 31.

    PubMed 27998223

  • Kantarjian HM, Stein AS, Bargou RC, Grande Garcia C, Larson RA, Stelljes M, Gokbuget N, Zugmaier G, Benjamin JE, Zhang A, Jia C, Topp MS. Blinatumomab treatment of older adults with relapsed/refractory B-precursor acute lymphoblastic leukemia: Results from 2 phase 2 studies. Cancer. 2016 Jul 15;122(14):2178-85. doi: 10.1002/cncr.30031. Epub 2016 May 3.

    PubMed 27143254

  • Talmadge JE, Donkor M, Scholar E. Inflammatory cell infiltration of tumors: Jekyll or Hyde. Cancer Metastasis Rev. 2007 Dec;26(3-4):373-400. doi: 10.1007/s10555-007-9072-0.

    PubMed 17717638

  • Thompson RH, Gillett MD, Cheville JC, Lohse CM, Dong H, Webster WS, Chen L, Zincke H, Blute ML, Leibovich BC, Kwon ED. Costimulatory molecule B7-H1 in primary and metastatic clear cell renal cell carcinoma. Cancer. 2005 Nov 15;104(10):2084-91. doi: 10.1002/cncr.21470.

    PubMed 16208700

  • McDermott DF, Atkins MB. PD-1 as a potential target in cancer therapy. Cancer Med. 2013 Oct;2(5):662-73. doi: 10.1002/cam4.106. Epub 2013 Jul 21.

    PubMed 24403232

  • Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph RW, Weber JS, Dronca R, Gangadhar TC, Patnaik A, Zarour H, Joshua AM, Gergich K, Elassaiss-Schaap J, Algazi A, Mateus C, Boasberg P, Tumeh PC, Chmielowski B, Ebbinghaus SW, Li XN, Kang SP, Ribas A. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013 Jul 11;369(2):134-44. doi: 10.1056/NEJMoa1305133. Epub 2013 Jun 2.

    PubMed 23724846

  • Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, Carcereny E, Ahn MJ, Felip E, Lee JS, Hellmann MD, Hamid O, Goldman JW, Soria JC, Dolled-Filhart M, Rutledge RZ, Zhang J, Lunceford JK, Rangwala R, Lubiniecki GM, Roach C, Emancipator K, Gandhi L; KEYNOTE-001 Investigators. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015 May 21;372(21):2018-28. doi: 10.1056/NEJMoa1501824. Epub 2015 Apr 19.

    PubMed 25891174

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Blinatumomab and Pembrolizumab in people with Leukemia, B-cell and Lymphoma, B-Cell, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 1 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Feasibility of combining pembrolizumab and blinatumomab (dose limiting toxicities) (time frame: 2 cycles of therapy (70 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03605589, which also lists 47 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2021.

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