Details

Details

Title S1312 testing the addition of Inotuzumab Ozogamicin to usual chemotherapy in relapsed and refractory acute leukemia

IRB S1312

CC 13-1292

Hospital Main Campus

Phase Phase 1

Disease Leukemia - Acute Lymphoblastic (ALL) , Leukemia - Acute Myeloid (AML)

Drug Inotuzumab Ozogamicin

Description

Description

Primary Objective
  1. To assess the safety of inotuzumab ozogamicin in combination with cyclophosphamide, vincristine and prednisone (CVP) and to determine the maximum tolerated dose (MTD) of inotuzumab ozogamicin in this regimen for patients with relapsed or refractory CD22+ acute leukemia (B-ALL, mixed phenotype, and Burkitt's).
Secondary Objectives
  1. To estimate the preliminary activity [response rate: complete remission (CR) + complete remission with incomplete count recovery (CRi)] of this combination in the expansion cohort.
  2. To estimate the frequency and severity of toxicities of this combination in this patient population.
Inclusion Criteria

Inclusion Criteria

Disease Related/Previous Therapy Criteria

  1. Patients must have a diagnosis of relapsed or refractory CD22-positive acute leukemia including B-ALL, mixed phenotype leukemia (biphenotypic), or Burkitt's leukemia based on WHO classification. Patients with bilineal leukemia are excluded.
  2. Patients must have evidence of acute leukemia in their peripheral blood or bone marrow. Patients must have ≥ 5% blasts in the peripheral blood or bone marrow within 14 days prior to registration. At least ≥ 20% of those blasts must be CD22-positive (surface) based on local immunophenotyping and histopathology.
  3. Patients must be refractory or have relapsed following prior Induction therapy. A standard Induction regimen is defined as any program of treatment that includes vincristine and prednisone or dexamethasone, cytarabine/anthracycline, or high dose cytarabine.
  4. For sites with the B1931022 pharmaceutical trial open, precursor B-cell ALL patients from that site may be eligible for S1312 providing they meet the following criteria:
    • Patient is in second salvage or more and B1931022 has been considered and ruled out as a treatment option;

      OR

    • Patient was treated on the standard of care arm of B1931022 and failed therapy.
  5. Patients may have received prior allogeneic transplant or autologous transplant. However, patients with prior allogeneic bone marrow transplant will be eligible only if both of the following conditions are met:
    • The transplant must have been performed ≥ 90 days prior to registration
    • The patient must not have ≥ Grade 2 acute graft versus host disease (GvHD) or either moderate or severe limited chronic GvHD within 14 days prior to registration.
  6. Patients known to have Ph+ ALL must have either failed treatment or been intolerant to treatment with at least two second or third generation tyrosine kinase inhibitors.
  7. Patients must not have received prior treatment with inotuzumab ozogamicin. Previous treatment with other anti-CD22 antibodies must have been completed at least 90 days prior to registration.
  8. Patients must have Zubrod Performance Status 0-2 (see Section 10.10).
  9. Patients must not have received any chemotherapy, investigational agents, or undergone major surgery within 14 days prior to registration with the following exceptions:
    • Monoclonal antibodies must not have been received for 42 days prior to registration.
    • Steroids, vincristine, 6-mercaptopurine, methotrexate, thioguanine and intrathecal chemotherapy are permitted within any time frame prior to registration.
  10. All drug-related toxicities must have resolved to ≤ Grade 2.

Clinical/Laboratory Criteria

  1. Patients must not have a systemic bacterial, fungal, or viral infection that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement despite appropriate antibiotics or other treatment).
  2. Patients must not have any other serious concurrent disease or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that would put the patient at undue risk of undergoing therapy.
  3. Patients must not have active CNS involvement (by clinical evaluation). Patients with previous documented history of CNS involvement of acute leukemia, or with clinical signs or symptoms consistent with CNS involvement of acute leukemia, must have a lumbar puncture which is negative for CNS involvement of acute leukemia. The lumbar puncture must be completed within 14 days prior to registration. Patients with no previous history of documented CNS involvement and with no clinical signs or symptoms consistent with CNS involvement are not required to have completed a lumbar puncture before registration. Note that treatment with intrathecal therapy is recommended during protocol treatment but CNS analysis during treatment is not required.
  4. Patients must be ≥ 18 years of age.
  5. Patients must have a peripheral blast count < 25,000/uL within 2 days prior to registration. (Treatment with hydroxyurea and steroids is permitted to bring the count down.)
  6. Patients must have serum creatinine ≤ 2 x institutional upper limits of normal (IULN) within 7 days prior to registration.
  7. Patients must have bilirubin ≤ 2 x IULN within 7 days prior to registration (unless the bilirubin is primarily unconjugated).
  8. Patients must have < Grade 2 neuropathy (sensory/motor) within 7 days prior to registration.
  9. Patients must have SGOT and SGPT ≤ 2.5 x IULN within 7 days prior to registration.
  10. Patients with a history of a serious allergic or anaphylactic reaction to humanized monoclonal antibodies are not eligible.
  11. Patients must not have a history of chronic or active hepatitis B or C infection. Patients must have negative Hepatitis B and C serologies performed within 28 days prior to registration.
  12. Patients must not have evidence or history of veno-occlusive disease or sinusoidal obstruction syndrome.
  13. Patients must not have a cardiac ejection fraction < 45% or the presence of New York Heart association stage III or IV heart failure within 14 days prior to registration (see Appendix 18.2). Either ECHO or MUGA may be used to determine ejection fraction.
  14. Patients must not have a myocardial infarction within 6 months prior to registration.
  15. Patients must not have a history of clinically significant arrhythmia, prolonged QTc interval, or unexplained syncope not thought to be vasovagal in nature within 6 months prior to registration.
  16. Patients must not have a screening QTcF interval > 500 milliseconds (by Fridericia calculation) based on the average of triplicate EKG performed within 7 days prior to registration. Note that triplicate EKG is required at other timepoints (see Section 7.1f).
  17. Patients must not have a history of chronic liver disease (or cirrhosis).
  18. Patients who are known to be HIV+ are eligible providing they meet all of the following additional criteria within 28 days prior to registration:
    • CD4+ cells ≥ 350/mm3 (nadir)
    • Viral load of < 50 copies HIV mRNA/mm3 if on cART or < 25,000 copies HIV mRNA if not on cART
    • No zidovudine or stavudine as part of cART
    Patients who are HIV+ and do not meet all of these criteria are not eligible for this study.
  19. Patients with evidence of extramedullary disease at diagnosis will have CT scan of the chest, abdomen and pelvis to obtain baseline values within 28 days prior to registration. See Section 7.1j for additional CT/MRI time points during treatment
  20. Patients must have complete history and physical examination within 28 days prior to registration.
  21. Patients must not be pregnant or nursing due to the unknown teratogenic effects of the study drug on an unborn child. Women/men of reproductive potential must have agreed to use an effective contraceptive method. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures.
  22. Prior malignancy other than acute leukemia is allowed, provided it is in remission and there is no plan to treat the malignancy at the time of registration.
  23. Pretreatment cytogenetics must be performed on all patients. Collection of pretreatment specimens must be completed within 14 days prior to registration to S1312. Specimens must be submitted to the site's preferred CLIA-approved cytogenetics laboratory (see Section 9.0). Reports of the results must be submitted as described in Sections 14.0 and 15.3. Note that cytogenetics are required at other timepoints (see Section 9.0).

Regulatory Criteria

  1. Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
  2. As a part of the OPEN registration process (see Section 13.5 for OPEN access instructions) the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.
  3. Patients planning to enroll in this study must first have a slot reserved in advance of the registration. All site staff will use OPEN to create a slot reservation (see Section 13.2 for OPEN slot reservation instructions).
Exclusion Criteria

Exclusion Criteria

Exclusion Criteria Not Available