A Study to Compare Blinatumomab Alone to Blinatumomab With Nivolumab in Patients Diagnosed With First Relapse B-Cell Acute Lymphoblastic Leukemia (B-ALL)

Study of Treatments for Relapsed B-Cell Acute Lymphoblastic Leukemia

S
Sandeep Batra, MD

Primary Investigator

Enrolling By Invitation
1 year - 30 years
All
Phase 2
461 participants needed
1 Location

Brief description of study

This phase II trial studies the effect of nivolumab in combination with blinatumomab compared to blinatumomab alone in treating patients with B-cell acute lymphoblastic leukemia (B-ALL) that has come back (relapsed). Down syndrome patients with relapsed B-ALL are included in this study. Blinatumomab is an antibody, which is a protein that identifies and targets specific molecules in the body. Blinatumomab searches for and attaches itself to the cancer cell. Once attached, an immune response occurs which may kill the cancer cell. Nivolumab is a medicine that may boost a patient's immune system. Giving nivolumab in combination with blinatumomab may cause the cancer to stop growing for a period of time, and for some patients, it may lessen the symptoms, such as pain, that are caused by the cancer.

THIS STUDY IS ENROLLING BY INVITATION ONLY - Consistent with most oncology trials, patients are not actively “recruited,” but are screened by their physician for appropriate clinical trial(s) at the time of their routine clinic visit. Occasionally, a patient may be a self-referral or physician referral, but are still screened for appropriate clinical trials at the time of their routine clinic visit. PI and staff may send copies of relevant consent forms to these patients to look over prior to actually consenting or enrolling them. This may take place at the patient's visit at which the consent is presented or the patient's next visit to the outpatient hematology/oncology clinic. 
 
Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:
IU Clinical Trials Office 
Phone: (317) 278-5632

Detailed description of study

PRIMARY OBJECTIVES:

I. To compare event free survival post reinduction (EFS PR) between blinatumomab vs. blinatumomab/nivolumab in Group 4 patients aged ≥ 1 to <31 years old with first relapse of CD19+ B ALL.

II. To compare EFS PR (EFS post-reinduction) between consolidation with blinatumomab vs. blinatumomab/nivolumab in Group 3 patients aged >= 1 to < 31 years old with first relapse of CD19+ B ALL.

SECONDARY OBJECTIVES:

I. To evaluate the safety and tolerability of blinatumomab/nivolumab in patients aged >= 1 to < 31 years old with first relapse of CD19+ B ALL.

EXPLORATORY OBJECTIVES:

I. In Group 4 patients, compare EFS PR between blinatumomab monotherapy and blinatumomab/nivolumab arms as compared to similar patients treated on the predecessor trial AALL1331.

II. In Group 4 patients, compare toxicity as defined by grade 3 or greater adverse events during the first cycle of blinatumomab or blinatumomab/nivolumab.

III. In Group 4 patients, compare MRD negative second remission (Rem-2) rate after the first cycle of immunotherapy between blinatumomab monotherapy and blinatumomab/nivolumab arms.

IV. In patients with Down syndrome (DS) with first relapse of B-ALL, describe the safety, tolerability and efficacy (as defined by MRD negative second remission, Rem-2) after up to two cycles of blinatumomab/nivolumab.

V. With each Group, perform subset analyses of EFS and overall survival (OS) based on features including degree of marrow disease at relapse, age, sex, body mass index, cytogenetics, site(s) of relapse, percent peripheral blasts at relapse and absolute lymphocyte count at first relapse.

OUTLINE:

Patients >= 18 years old with marrow +/- extramedullary (EM) relapse of any duration after initial diagnosis, or patients < 18 years old with marrow +/- EM relapse < 24 months after initial diagnosis are assigned to Group 1. Patients < 18 years old with marrow +/- EM relapse >= 24 months from initial diagnosis, or all isolated extramedullary (IEM) relapses >= 1 to < 31 years old are assigned to Groups 2-3 re-induction. Patients with DS are assigned to Arm G. NOTE: Patients in Group 1 and DS patients with white blood cells (WBC) >= 30,000/uL, CNS 2/3 disease, or testicular disease must first receive 1 of 3 pre-immunotherapy treatments.

Starting with amendment 4C (9/19/2024), patients with DS are assigned to group 3 or 4. Patients < 18 years with bone marrow first relapse ≥ 36 months from initial diagnosis with MRD <0.1% after VXLD reinduction or with isolated CNS/testicular extramedullary relapse occurring ≥ 18 months from initial diagnosis with MRD <0.1% after VXLD reinduction are assigned to group 3. Patients who do not meet criteria for group 3 will be assigned to group 4. Patients with Down syndrome ≥ 1 to < 31 years of age with first bone marrow relapse of B ALL are assigned to arm G.

PRE-IMMUNOTHERAPY TREATMENT FOR PATIENTS WITH WBC >= 30,000/uL (CLOSED TO ACCRUAL 9/19/2024 EXCEPT FOR ARM G) : Patients receive methotrexate (MTX) intrathecally (IT) or cytarabine IT or intrathecal triple therapy (ITT) consisting of MTX, hydrocortisone sodium succinate, and cytarabine IT at the time of diagnostic lumbar puncture (LP) or on day 1 (if intrathecal therapy is given with relapse diagnostic LP < 7 days prior to the start of protocol therapy). Patients also receive dexamethasone intravenously (IV) or orally (PO) twice daily (BID) on days 1-5, vincristine sulfate via infusion or IV push over 1 minute on day 1. Patients with DS also receive leucovorin calcium PO or IV every 6 hours (q6h) for 2 doses on day 2 or at 24 and 30 hours after each IT administration. Patients should proceed to the next cycle when CNS 1 and no testicular disease is present, no sooner than Day 8 and no later than Day 15.

PRE-IMMUNOTHERAPY TREATMENT FOR CNS 2/3 DISEASE (CLOSED TO ACCRUAL 9/19/2024 EXCEPT FOR ARM G): Patients receive MTX IT or cytarabine IT twice weekly (Q2W) for 5-7 doses or Intrathecal Triple Therapy (ITT) IT Q2W for 3-4 doses until patient is CNS 1. Patients with DS also receive leucovorin calcium PO or IV q6h for 2 doses at 24 and 30 hours after each IT administration. Patients should proceed to the next cycle when CNS 1 and no testicular disease is present, no sooner than Day 15 and no later than Day 24.

PRE-IMMUNOTHERAPY TREATMENT FOR TESTICULAR DISEASE(CLOSED TO ACCRUAL 9/19/2024 EXCEPT FOR ARM G): Patients receive MTX IT, cytarabine IT, or ITT IT on days 1 and 15 (day 1 may be omitted if intrathecal therapy is given with relapse diagnostic LP < 7 days prior to the start of protocol therapy). Patients with DS also receive leucovorin calcium PO or IV q6h for 2 doses on days 2 and 16 or at 24 and 30 hours after each IT administration. Males with testicular disease at relapse undergo radiation once daily (QD) for a total of 12 fractions over 12 days. Patients should proceed to the next cycle when CNS 1 and no testicular disease is present, no sooner than Day 15 and no later than Day 22.

GROUP 1 (CLOSED TO ACCRUAL 9/19/2024): Patients are randomized to Arm A or Arm B.

ARM A: Patients receive dexamethasone PO or IV on days 1 and 8 of cycle 1, blinatumomab via continuous IV infusion on days 1-28 of cycles 1-2, MTX IT, cytarabine IT, or ITT IT on days 1, 15, and 36 of cycle 1 (MTX, cytarabine, and ITT on day 1 may be omitted if intrathecal therapy was given < 7 days prior to the start of this cycle), and MTX IT, cytarabine IT, or ITT IT on days 15 and 36 of cycle 2. Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity. NOTE: Patients with MRD < 0.01% after cycle 1 may stop study treatment or may choose to continue to cycle 2. Patients with MRD >= 0.01% after cycle 1 proceed to cycle 2.

ARM B: Patients receive dexamethasone, blinatumomab, and MTX, cytarabine, or ITT as in Arm A. Patients also receive nivolumab IV over 30 minutes on days 11 and 25 of cycle 1 and days 1 and 15 of cycle 2. Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity. NOTE: Patients with MRD < 0.01% after cycle 1 may stop study treatment or may choose to continue to cycle 2. Patients with MRD >= 0.01% after cycle 1 proceed to cycle 2.

GROUPS 2-4 VXLD REINDUCTION: Patients receive vincristine sulfate via infusion or IV push over 1 minute on days 1, 8, 15, and 22, dexamethasone PO or IV on days 1-14, doxorubicin hydrochloride IV over 1-15 minutes on day 1, MTX IT on days 1, 8, and 29 (day 1 IT may be omitted if intrathecal therapy is given with relapse diagnostic LP < 7 days prior to the start of this cycle) (days 8 and 29 for CNS 1 patients at relapse only), pegaspargase intramuscularly (IM) or IV over 1-2 hours on days 2 and 16 or calaspargase IV over 1-2 hours on day 2 (for patients ≤ 22 years), cytarabine IT on days 4 and 11 (CNS 2 patients at relapse only), then Q2W until 3 consecutive samples are clear of blasts, and ITT IT on days 8, 15, 22, and 29 (CNS 3 patients at relapse only). Treatment continues in the absence of disease progression or unacceptable toxicity.

GROUP 2 (CLOSED TO ACCRUAL 9/19/2024): The following patients are randomized to Arm C or Arm D: 1) >= 1 to < 31 years old, IEM relapse < 18 months from diagnosis, regardless of MRD after Re-Induction. 2) < 18 years old with marrow relapse >= 24 to < 36 months from diagnosis regardless of MRD after Re-Induction, 3) >= 1 to < 31 years old, IEM relapse >= 18 months, and MRD >= 0.1% after Re-Induction, 4) < 18 years old with marrow relapse >= 36 months, and MRD >= 0.1% after Re-Induction.

ARM C: Patients receive dexamethasone PO or IV on day 1 of cycle 1, blinatumomab via continuous IV infusion on days 1-28 of cycles 1 and 2, and MTX IT on days 1 and 15 of cycles 1 and 2 (day 1 may be omitted from cycle 1 if intrathecal MTX is given < 7 days prior to the start of cycle 1 ). Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity. NOTE: Patients with MRD < 0.01% after cycle 1 may stop study treatment or may choose to continue to cycle 2. Patients with MRD >= 0.01% after cycle 1 proceed to cycle 2.

ARM D: Patients receive dexamethasone, blinatumomab, and MTX as in Arm C. Patients also receive nivolumab IV over 30 minutes on days 11 and 25 of cycle 1 and days 1 and 15 of cycle 2. Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity. NOTE: Patients with MRD < 0.01% after cycle 1 may stop study treatment or may choose to continue to cycle 2. Patients with MRD >= 0.01% after cycle 1 proceed to cycle 2.

GROUP 3: Patients are randomized to Arm E or Arm F.

ARM E:

IMMUNOTHERAPY CYCLES 1-2: Patients receive dexamethasone PO or IV on day 1 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28, and MTX IT on days 1 and 15 (day 1 may be omitted from cycle 1 if intrathecal therapy is given < 7 days prior to the start of this cycle). Immunotherapy cycles 1-2 alternate with Consolidation cycles 1-2.

CONSOLIDATION: Patients receive dexamethasone PO or IV on days 1-5, methotrexate IV, over 24 hours, on days 8 and 22, methotrexate IT on days 8 and 22 (CNS 1/2 at relapse only) or ITT IT on days 8 and 22 (CNS 3 at relapse only).

INTENSIFICATION CYCLES 1-2: Patients receive dexamethasone PO on days 1-5, vincristine sulfate IV push over 1 minute or via infusion on day 1, mercaptopurine PO on days 1-42, methotrexate IV over 24 hours on days 8 and 22, cytarabine IV, over 3 hours on days 43 and 44, asparaginase erwinia recombinant IM or crisantaspase/asparaginase erwinia IM or IV over 1-2 hours on day 44, methotrexate IT on days 1 and 43 (CNS 1/2 at relapse only) or ITT IT on days 1 and 43 (CNS 3 at relapse only).

IMMUNOTHERAPY CYCLE 3: Patients receive blinatumomab IV via continuous infusion on days 1-28, and MTX IT on days 1 and 15 (CNS 1/2 at relapse only) or ITT IT on days 1 and 15 (CNS 3 at relapse only).

MAINTENANCE: Patients receive dexamethasone PO BID on days 1-5, 29-33, and 57-61, vincristine sulfate IV push over 1 minute or via infusion on days 1, 29, and 57, mercaptopurine PO on days 1-84, MTX IT on day 1 (CNS 1/2 patients at relapse only), ITT IT on day 1 (CNS 3 patients at relapse only), and MTX PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 12 weeks for 2 years from the start of Re-Induction therapy in the absence of disease progression or unacceptable toxicity.

MAINTENANCE CHEMORADIATION (FOR CNS 3 PATIENTS ONLY): Beginning between the first and second cycles of maintenance therapy, patients receive dexamethasone PO BID on days 1-7 and 15-21, vincristine sulfate IV push over 1 minute or via infusion on days 1, 8, and 15, and pegaspargase IM or IV over 1-2 hours or calaspargase IV over 1-2 hours on day 1. Patients with CNS 3 and isolated CNS relapse undergo cranial radiation in the form of 3-dimensional (D)-conformal radiation therapy (CRT) over 5 days per week for a total of 10 treatments.

ARM F:

IMMUNOTHERAPY CYCLES 1-2: Patients receive dexamethasone PO or IV on day 1 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28, nivolumab IV over 30 minutes on days 11 of cycle 1 and on days 1 of cycles 2 and 3, and MTX IT on days 1 and 15 (CNS 1/2 patients at relapse only)(day 1 may be omitted from cycle 1 if intrathecal therapy is given with < 7 days prior to the start of this cycle) or , ITT IT on day 1 (CNS 3 patients at relapse only) (day 1 may be omitted from cycle 1 if intrathecal therapy is given with < 7 days prior to the start of this cycle). Immunotherapy cycles 1-2 alternate with Consolidation cycles 1-2.

CONSOLIDATION CYCLES 1-2: Patients receive dexamethasone PO on days 1-5, vincristine sulfate IV push over 1 minute or via infusion on day 1, methotrexate IV, over 24 hours, on days 8 and 22, methotrexate IT on days 8 and 22 (CNS 1/2 at relapse only) or ITT IT on days 8 and 22 (CNS 3 at relapse only).

INTENSIFICATION CYCLES 1-2: Patients receive dexamethasone PO on days 1-5, vincristine sulfate IV push over 1 minute or via infusion on day 1, mercaptopurine PO on days 1-42, methotrexate IV over 24 hours on days 8 and 22, cytarabine IV, over 3 hours on days 43 and 44, asparaginase erwinia recombinant IM or crisantaspase/asparaginase erwinia IM or IV over 1-2 hours on day 44, methotrexate IT on days 1 and 43 (CNS 1/2 at relapse only) or ITT IT on days 1 and 43 (CNS 3 at relapse only).

IMMUNOTHERAPY CYCLE 3: Patients receive blinatumomab IV via continuous infusion on days 1-28, nivolumab IV over 30 minutes on days 1 and 15 and MTX IT on days 1 and 15.

MAINTENANCE: Patients receive dexamethasone PO BID on days 1-5, 29-33, and 57-61, vincristine sulfate IV push over 1 minute or via infusion on days 1, 29, and 57, mercaptopurine PO on days 1-84, MTX IT on day 1 (CNS 1/2 patients at relapse only), ITT IT on day 1 (CNS 3 patients at relapse only), and MTX PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78. Treatment repeats every 12 weeks for 2 years from the start of Re-Induction therapy in the absence of disease progression or unacceptable toxicity.

MAINTENANCE CHEMORADIATION (FOR CNS 3 PATIENTS): Beginning between the first and second cycles of maintenance therapy, patients receive dexamethasone PO BID on days 1-7 and 15-21, vincristine sulfate IV push over 1 minute or via infusion on days 1, 8, and 15, and pegaspargase IM or IV over 1-2 hours or calaspargase IV over 1-2 hours on day 1. Patients with CNS 3 and isolated CNS relapse undergo cranial radiation in the form of 3-dimensional (D)-conformal radiation therapy (CRT) over 5 days per week for a total of 10 treatments.

GROUP 4: Patients are randomized to arm H or arm I.

ARM H: Patients receive dexamethasone PO or IV on day 1 and 8 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28 and MTX IT on days 1 of cycle 1 only and days 15 and 36 ( for patients with CNS1/2 at relapse only) or ITT on day 1 of cycle 1 only and days 15 and 36 (for patients with CNS 3 at relapse only) (day 1 IT therapy may be omitted from cycle 1 if intrathecal therapy is given with < 7 days prior to the start of this cycle). Cycles repeat every 36 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

ARM I: Patients receive dexamethasone PO or IV on day 1 and 8 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28, nivolumab IV, over 30 minutes on day 11 of cycle 1 and day 3 of cycle 2 and MTX IT on days 1 of cycle 1 only and days 15 and 36 ( for patients with CNS 1/2 at relapse only) or ITT on day 1 of cycle 1 only and days 15 and 36 (for patients with CNS 3 at relapse only) (day 1 IT therapy may be omitted from cycle 1 if intrathecal therapy is given with < 7 days prior to the start of this cycle). Cycles repeat every 36 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

ARM G (DS PATIENTS): Patients receive dexamethasone PO or IV on days 1 and 8 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28, nivolumab IV over 30 minutes on days 11 of cycle 1 and day 3 of cycle 2, and MTX IT (for patients with CNS 1/2 at relapse only) or ITT on day 1 of cycle 1 only and days 15 and 36 (for patients with CNS 3 at relapse only) (day 1 IT therapy may be omitted from cycle 1 if intrathecal therapy is given with < 7 days prior to the start of this cycle). Cycles repeat every 37 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

Patients undergo lumbar puncture, bone marrow biopsy and aspiration, and collection of blood, urine and cerebrospinal fluid throughout the study.

After completion of study treatment, patients are followed up every 3 months for 1 year.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Down Syndrome, Recurrent B Acute Lymphoblastic Leukemia, Riley
  • Age: 1 year - 30 years
  • Gender: All

Inclusion Criteria:

  • Patients must be >= 1 and < 31 years at time of enrollment

  • Patients must have first relapse of CD19+ B-ALL (relapse blasts must express CD19) in one of the following categories:

    • Isolated bone marrow relapse
    • Isolated central nervous system (CNS) (excluding known optic nerve/retinal and CNS chloromas) and/or testicular relapse
    • Combined bone marrow with extramedullary relapse in the CNS (excluding known optic nerve/retinal and CNS chloromas) and/or testes

  • Patients with Down syndrome (DS) are eligible in the following categories:

    • Isolated bone marrow relapse
    • Combined bone marrow with CNS (excluding known optic nerve/retinal and CNS chloromas) and/or testicular relapse

  • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age

    • Of note, for patients with developmental delay (e.g., Down syndrome) regardless of age, Lansky scale may be substituted for Karnofsky scale. However, the requirement for ECOG 0-2 remains, regardless of known history of developmental delay

  • Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study

    • Patients with prior blinatumomab or CD19+ chimeric antigen receptor therapy in the upfront setting will be eligible, provided relapsed lymphoblasts retain CD19 expression
    • Patients must not have had a prior hematopoietic stem cell transplant
    • A single intrathecal chemotherapy at the time of relapse will be allowed. If < 7 days have elapsed between this intrathecal therapy (IT) and the start of protocol therapy, then the day 1 intrathecal chemotherapy (i.e. methotrexate, cytarabine, or triple intrathecal) may be omitted

    • In the 28 days prior to enrollment, up to five days of post-relapse, pre-enrollment therapy (steroids and/or hydroxyurea only) is permissible

      • Patients with Down syndrome who received pre-enrollment therapy and have a white blood count (WBC) >= 30,000/ul at the time of enrollment still must receive protocol specified cytoreductive therapy with vincristine and dexamethasone, and no "washout" is required
      • Patients with Down syndrome who received pre-enrollment therapy and have a WBC < 30,000/ul at the time of enrollment must be given a 24 hour "washout" before starting immunotherapy
    • Note: There is no waiting period or "washout" for patients who relapse while receiving upfront therapy

  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR a serum creatinine based on age/sex as follows (within 7 calendar days prior to enrollment):

    • Age: Maximum serum creatinine (mg/dL)

      • 1 to < 2 years: 0.6 (male), 0.6 (female)
      • 2 to < 6 years: 0.8 (male), 0.8 (female)
      • 6 to < 10 years: 1 (male), 1 (female)
      • 10 to < 13 years: 1.2 (male), 1.2 (female)
      • 13 to < 16 years: 1.5 (male), 1.4 (female)

      • >= 16 years: 1.7 (male), 1.4 (female)

        • The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Center for Disease Control (CDC)
  • Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by echocardiogram, cardiac magnetic resonance imaging (MRI) or radionuclide angiogram
  • No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if there is clinical indication for determination
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

  • Patients with B-lymphoblastic lymphoma (B-LLy)
  • Patients with Burkitt leukemia/lymphoma or mature B-cell leukemia
  • Patients with Philadelphia chromosome positive (Ph+) B-ALL
  • Patients with mixed phenotype acute leukemia (MPAL)
  • Patients with known Charcot-Marie-Tooth disease
  • Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL, regardless of blast immunophenotype

  • Patients with active, uncontrolled infection defined as:

    • Positive bacterial blood culture within 48 hours of study enrollment
    • Receiving IV or PO antibiotics for an infection with continued signs or symptoms. Note: Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection if cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved. For patients with clostridium (C.) difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed and stools must have normalized to baseline.
    • Fever above 38.2 degrees Celsius (C) within 48 hours of study enrollment with clinical signs of infection. Fever without clinical signs of infection that is attributed to tumor burden is allowed if blood cultures are negative for > 48 hours
    • A positive fungal culture within 30 days of study enrollment or active therapy for presumed invasive fungal infection
    • Active viral or protozoal infection requiring IV treatment
  • Patients known to have one of the following concomitant genetic syndromes: Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome are not eligible.
  • Patients with uncontrolled HIV, hepatitis B, or hepatitis C infection. Of note, patients with known human immunodeficiency virus (HIV) infection on effective anti-retroviral therapy with undetectable viral load for at least the last 6 months prior to enrollment are eligible. Similarly, hepatitis B and hepatitis C positive patients who have been treated and have no viral detectable burden are also eligible

  • Patients with significant central nervous system pathology that would preclude treatment with blinatumomab, including history of severe neurologic disorder or autoimmune disease with CNS involvement

    • Note: Patients with a history of seizures that are well controlled on stable doses of anti-epileptic drugs are eligible Patients with a history of cerebrovascular ischemia/hemorrhage with residual deficits are not eligible. Patients with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved
  • Patients with an active known/suspected autoimmune disease are not eligible. However, patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll

  • Group 4 and patients with DS patients with known non-hematopoietic, non-CNS/testicular extramedullary disease (i.e., chloromatous disease) are not eligible

    • Note: Group 3 patients with known non-hematopoietic, non-CNS/testicular extramedullary disease (i.e., chloromatous disease) are eligible if this is NOT the only site of relapsed disease
  • Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained within 7 days prior to enrollment. Patients who are sexually active and of reproductive potential are not eligible unless they agree to use an effective contraceptive method for the duration of this study. Men with female partners of childbearing potential should use effective contraception during the duration of their treatment. The effect of blinatumomab on fertility has not been evaluated. Blinatumomab is not recommended for pregnant women or women of childbearing potential (WOCBP) not using contraception. Females of reproductive potential must use effective contraception during treatment and for at least 48 hours after the last dose of blinatumomab. Studies in animal models have shown that nivolumab can adversely impair pregnancy. Thus, nivolumab is expected to cause fetal harm during pregnancy. WOCBP receiving nivolumab must continue contraception for a period of at least 5 months after the last dose of nivolumab. It is unknown whether nivolumab is present in breast milk, thus breastfeeding should be discontinued while a patient is receiving nivolumab
  • Lactating females are not eligible unless they agree to not breastfeed their infants. It is unknown whether blinatumomab or its metabolites are excreted in human breast milk. Women are not permitted to breastfeed while receiving blinatumomab and for the last 48 hours after the last blinatumomab dose. Due to the potential for serious adverse reactions in the breastfed infant, women are not permitted to breastfeed during treatment and for 5 months after the last nivolumab dose

Updated on 01 Jul 2025. Study ID: PHO-COG-AALL1821, NCI-2020-06813, 10949

This study investigates the effects of two investigational medications, blinatumomab and nivolumab, in patients with B-cell acute lymphoblastic leukemia (B-ALL) that has relapsed. B-ALL is a type of cancer that affects the white blood cells. The study includes patients with Down syndrome and aims to compare the outcomes of using blinatumomab alone versus a combination of blinatumomab and nivolumab. Blinatumomab is a protein that targets cancer cells to stimulate an immune response, while nivolumab is a drug that may enhance the immune system's ability to fight cancer.

Participants in the study will be divided into different study arms based on their age, type of relapse, and other medical conditions. The study involves receiving medications such as blinatumomab and nivolumab through intravenous infusions, as well as other treatments like dexamethasone and methotrexate. Some patients may also undergo procedures like lumbar punctures and bone marrow biopsies. The study will monitor the safety and effectiveness of these treatments in stopping the growth of cancer cells and improving patient outcomes.

  • Who can participate: Participants must be between 1 and 30 years old and have a first relapse of CD19+ B-ALL. Eligibility includes isolated bone marrow relapse or combined bone marrow with CNS or testicular relapse; patients with Down syndrome are also eligible under specific criteria.
  • Study details: Participants will receive investigational medications through intravenous infusions. Some will receive blinatumomab alone, while others will receive it in combination with nivolumab. A placebo is not used in this study.
Please visit our main page to search for other studies you may be interested in. If you need help finding a study or have any questions, please contact us at inhealth@iu.edu

Interested in the study?

This study is accepting only persons who receive care at a certain clinic or doctor or who are part of an invited group. Questions about this study can be directed to the study team listed in the description or contact your doctor to see if you are eligible.

Accepting Referrals by Invitation Only