Clinical Trials /

Fractionated Gemtuzumab Ozogamicin Followed by Non-engraftment Donor Leukocyte Infusions for Relapsed/Refractory Acute Myeloid Leukemia

NCT03374332

Description:

This study includes patients with relapsed acute leukemia who have previously been treated with standard treatment that is still present and there is no curative treatment option available. Researchers are studying whether the drug Gemtuzumab Ozogamicin, followed by an infusion of blood cells called leukocytes from a donor, can stimulate the immune system to potentially fight the leukemia. Gemtuzmab ozogamicin is a class of drugs known as an antibody drug conjugate. The drug is given on days 1,4,7. It is infused, attaches to cells with a certain marker on the surface (the majority of which would be leukemia cells). The drug is then internalized and the chemotherapy drug becomes activated. Gemtuzumab is currently FDA approved for the treatment of acute myeloid leukemia. The infusion of leukocytes to stimulate the immune system to fight your leukemia is investigational and has not been proven to cure cancer. This combination of Gemtuzumab Ozogamicin and donor leukocytes is not an FDA approved treatment and is investigational. Initially a total of 6 patients will be included in the study to assess the safety of the treatment. Once 6 patients have been treated and no unacceptable toxicities are seen, more patients will be enrolled. The study will treat up to 18 patients on the study.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Fractionated Gemtuzumab Ozogamicin Followed by Non-engraftment Donor Leukocyte Infusions for Relapsed/Refractory Acute Myeloid Leukemia
  • Official Title: Fractionated Gemtuzumab Ozogamicin Followed by Non-engraftment Donor Leukocyte Infusions for Relapsed/Refractory Acute Myeloid Leukemia

Clinical Trial IDs

  • ORG STUDY ID: BrUOG 345
  • NCT ID: NCT03374332

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
Gemtuzumab Ozogamicin (GO)MylotargTreatment #2: Gemtuzumab Ozogamicin and DLI

Purpose

This study includes patients with relapsed acute leukemia who have previously been treated with standard treatment that is still present and there is no curative treatment option available. Researchers are studying whether the drug Gemtuzumab Ozogamicin, followed by an infusion of blood cells called leukocytes from a donor, can stimulate the immune system to potentially fight the leukemia. Gemtuzmab ozogamicin is a class of drugs known as an antibody drug conjugate. The drug is given on days 1,4,7. It is infused, attaches to cells with a certain marker on the surface (the majority of which would be leukemia cells). The drug is then internalized and the chemotherapy drug becomes activated. Gemtuzumab is currently FDA approved for the treatment of acute myeloid leukemia. The infusion of leukocytes to stimulate the immune system to fight your leukemia is investigational and has not been proven to cure cancer. This combination of Gemtuzumab Ozogamicin and donor leukocytes is not an FDA approved treatment and is investigational. Initially a total of 6 patients will be included in the study to assess the safety of the treatment. Once 6 patients have been treated and no unacceptable toxicities are seen, more patients will be enrolled. The study will treat up to 18 patients on the study.

Trial Arms

NameTypeDescriptionInterventions
Treatment 1: Gemtuzumab Ozogamicin and DLI >or =70 years oldExperimentalPatients > 70 years of age will be given gemtuzumab ozogamicin 6mg/m2 (2mg/m2 each day, capped at 4.5mg) from Day 1, 4, 7. Day 8: The product will be administered unprocessed on day 8 (same day as leukapheresis) with a minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg irrespective of the number of CD34+ cells.
  • Gemtuzumab Ozogamicin (GO)
Treatment 1 : Gemtuzumab Ozogamicin and DLI < 70 years oldExperimentalPatients > 70 years of age will be given gemtuzumab ozogamicin 9mg/m2 (3mg/m2 each day,capped at 4.5mg) from Day 1, day 4, day 7 Day 8: The product will be administered unprocessed on day 8 (same day as leukapheresis) with a minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg irrespective of the number of CD34+ cells.
  • Gemtuzumab Ozogamicin (GO)
Treatment #2: Gemtuzumab Ozogamicin and DLIExperimentalPatients who show a transient response to therapy can receive up to two additional donor leukocyte infusions with GO 6mg/m2 (2mg/m2 day,capped at 4.5mg) for all patients regardless of age administered day 1, 4, 7, no sooner than 35 days status post their last cellular infusion. Day 8: The product will be administered unprocessed on day 8 (same day as leukapheresis) with a minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg irrespective of the number of CD34+ cells.
  • Gemtuzumab Ozogamicin (GO)
Treatment #3: Gemtuzumab Ozogamicin and DLIExperimentalPatients who show a transient response to therapy can receive up to two additional donor leukocyte infusions with GO 6mg/m2 (2mg/m2 each day, capped at 4.5mg) for all patients regardless of age administered day 1,4,7, no sooner than 35 days status post their last cellular infusion. Day 8: The product will be administered unprocessed on day 8 (same day as leukapheresis) with a minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg irrespective of the number of CD34+ cells.
  • Gemtuzumab Ozogamicin (GO)

Eligibility Criteria

        Inclusion Criteria:

          -  Histologic confirmation of acute myeloid leukemia (AML)

          -  Recurrence or progression (including refractory disease) of AML after at least 1 prior
             standard treatment with progression within 6 months from last treatment.

          -  No curative treatment option is available

             -> 4-weeks since prior chemotherapy or radiation to cellular therapy infusion.

          -  Age equal to or greater than 18 years.

          -  Patients with a history of invasive second malignancy who are disease free for > 2
             years.

          -  Patients must have an expected life expectancy of at least 2 months at the time of
             initiation of treatment

          -  No active systemic infections allowed.

          -  Patients who have relapsed after standard autologous stem cell infusion are eligible
             as long as they meet all inclusion criteria and no exclusion criteria. These patients
             must be out more than 6 months from cell infusion to be eligible for enrollment.

          -  DLCO > 40% with no symptomatic pulmonary disease.

          -  LVEF > 40% by MUGA or echocardiogram.

          -  Creatinine <1.5x ULN or any serum creatinine level associated with a measured or
             calculated creatinine clearance of >40 mL/min, AST and ALT < 2.5x ULN, Total Bilirubin
             < 2 x ULN

          -  Women of childbearing potential and sexually active males must use 2 forms of
             effective contraception method from time of consent through 6 months after completing
             treatment (whether last treatment is infusion or drug).

          -  Not pregnant or nursing. Women of child bearing potential must have a negative serum
             or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG)
             within 7 days prior to beginning of treatment (drug). Post-menopausal women (surgical
             menopause or lack of menses >12 months) do not need to have a pregnancy test, please
             document status.

          -  Performance status < 2 (or KPS 70)

        Exclusion Criteria:

          -  Evidence of HIV infection.

          -  Any uncontrolled severe, concurrent illness which in the opinion of the treating
             physician would make this protocol treatment unreasonably hazardous for the patient.

          -  Oxygen dependent obstructive pulmonary disease.

          -  Failure to demonstrate adequate compliance with medical therapy and follow-up

          -  Significant medical or psychiatric illness that would impair the ability to
             participate in protocol therapy.

          -  Previous allogeneic stem cell transplant

          -  Patients who have had previous purine analog (fludarabine, pentostatin, 2-CDA)
             treatment or treatment with alemtuzumab within 1 year of entering the study

          -  Previous history of Veno-occlusive disease/Sinusoidal Obstruction Syndrome

          -  Active hepatitis B or C

          -  Patients with known active central nervous system leukemia

          -  Patients with prior treatment of Gemtuzumab ozogamicin
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response Rate
Time Frame:Post infusion for a total of 2 years.
Safety Issue:
Description:Response rate of infusional gemtuzumab ozogamicin followed by nonengraftment donor leukocyte infusions in patients with refractory acute myeloid leukemia. Bone Marrow Biopsy to be done in patients thought to have responded.

Secondary Outcome Measures

Measure:Survival
Time Frame:Through 2 years post end of treatment
Safety Issue:
Description:Progression free survival and overall survival of infusional gemtuzumab ozogamicin followed by nonengraftment donor leukocyte infusions in patients with refractory acute myeloid leukemia.
Measure:Dose limiting toxicities
Time Frame:Start of treatment through 16 weeks post the final infusion
Safety Issue:
Description:Rate of dose limiting toxicities of gemtuzumab ozogamicin followed by nonengraftment donor leukocyte infusions in patients with refractory acute myeloid leukemia.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:John Reagan

Trial Keywords

  • Refractory
  • progression
  • recurrence

Last Updated

January 14, 2019