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 1: Gemtuzumab Ozogamicin and DLI Dose Level 1

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 Dose Level 1ExperimentalPatients ≥70 years old: GO 6mg/m2 (2mg/m2 each dose) Patients < 70 years old: GO 9mg/m2 (3mg/m2 each dose) Day 8: The product will be administered unprocessed on day 8 (same day as leukapheresis) with a minimum of 1x10^7 CD3+ cells and maximum of 2x10^7 CD3+ cells/kg irrespective of the number of CD34+ cells. Patients 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 on days 1,4, and 7, no sooner than 35 days status post their last cellular infusion.
  • Gemtuzumab Ozogamicin (GO)
Treatment 2: Gemtuzumab Ozogamicin and DLI Dose Level 2ExperimentalPatients ≥70 years old: GO 6mg/m2 (2mg/m2 each dose) Patients: < 70 years old: GO 9mg/m2 (3mg/m2 each dose) Day 8: The product will be administered unprocessed on day 8 (same day as leukapheresis) with a minimum of 1x10^8 CD3+ cells and maximum of 2x10^8 CD3+ cells/kg irrespective of the number of CD34+ cells. Patients 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 on days 1,4, and 7, no sooner than 35 days status post their last cellular infusion.
  • Gemtuzumab Ozogamicin (GO)

Eligibility Criteria

        Inclusion Criteria of Recipient (patient):

          -  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
             < 1.5 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 of Recipient (patient):

          -  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

          -  Patients eligible for allogeneic stem cell transplant

        Donor Eligibility Criteria * donor eligibility must be documented and assessed by a
        separate participating physician other than the treating physician of the recipient.

          -  Donors agree to up to 3 donor leukocyte collections as documented by assessing
             physician (although it is not required that the same donor is used for all leukocyte
             infusions it is preferable, therefore agreement is important at screening). This must
             be documented in writing by treating physician.

          -  Typing is required at the following loci: HLA A, B, C, and DRB1.

          -  Patients with a HLA 0/6 to 3/6(using loci A, B, DR) donor match will be able to
             participate in this protocol.

          -  Donors must be a first degree relative.

          -  CMV titer negative donors are preferred above CMV titer positive donors if the patient
             is CMV positive. If the patient is CMV negative, only CMV negative donors are
             eligible.

          -  Although ABO blood type matching is not required given use of apheresis product
             preference will be made to ABO compatible donors

          -  Donors must be ≥18 years of age to donate.

          -  Donor with a history of malignancy other than non-melanoma skin cancers are eligible
             only if they had a history of a solid tumor malignancy more than five years prior to
             lymphocyte donation, and are considered to be in longstanding complete remission as
             documented by a physician. The donor must be healthy and have all testing criteria
             completed and meet all criteria for stem cell donation.

          -  The donor will also be assessed by physician who will document behavioral risk for
             exposure to infectious agents and diseases.Testing will include the following: Human
             transmissible spongiform encephalopathy, including Creutzfeldt-Jakob disease,
             communicable disease risks associated with xenotransplantation, Chlamydia trachomatis
             and for Neisseria gonorrhea, Treponema pallidum (syphilis).This will exclude the
             donor.

          -  The donor must be in good general health and not have significant cardiopulmonary,
             renal, endocrine, or hepatic disease as documented in writing by physician.

          -  B-HCG urine or serum negative if donor is of childbearing potential within 7 days of
             PBMC procurement. Not applicable for donors who are Post-menopausal (surgical
             menopause or lack of menses ≥12 months).

          -  Donors must have adequate venous access so leukapheresis can be performed via standard
             peripheral IV without the need for placement of a central venous catheter.

        Donor Exclusion Criteria:

          -  HLA to which the patient has anti-HLA antibody (ies)

          -  Evidence of infection for HIV-1, HIV-2, syphilis, hepatitis B or C, HTLV 1 or 2, WNV,
             Chagas, Zika.

          -  Uncontrolled diabetes mellitus. If donor has controlled diabetes this must be
             documented by physician.

          -  Active or congestive heart failure syndrome from any cause per donor medical history.
             Approval for participation by Cardiologist required to be sent to BrUOG.

          -  Full cardiac workup by a Cardiologist is required for any history of congestive heart
             failure syndrome, conduction abnormalities or history of arrhythmia other than treated
             atrial fibrillation.

          -  Active angina pectoris. To be documented by physician

          -  Oxygen dependent pulmonary disease. To be documented by physician

          -  History of any lymphoid, myeloid or other non-solid malignancy. To be documented by
             physician

          -  Failure to receive full informed consent.

          -  Inadequate renal and/or hepatic function per medical history. To be documented by
             physician

          -  Known history of cirrhosis or active liver disease per medical history. To be
             documented by physician

          -  History of transplantation. To be documented by physician.

          -  Donor with a diagnosis of Zika in the past 6 months, or who lived in or traveled to an
             area with increased risk for Zika in the past 6 months, or who had sex in the past 6
             months with a person who has the risks of either having been diagnosed or lived in or
             traveled to areas with increased risk.

          -  A donor in whom plasma dilution sufficient to affect the results of communicable
             disease testing is suspected, unless: (A) You test a specimen taken from the donor
             before transfusion or infusion and up to 7 days before recovery of cells or tissue; or
             (B) You use an appropriate algorithm designed to evaluate volumes administered in the
             48 hours before specimen collection, and the algorithm shows that plasma dilution
             sufficient to affect the results of communicable disease testing has not occurred.

          -  Clinical situations in which you must suspect plasma dilution sufficient to affect the
             results of communicable disease testing will exclude the donor. Such situations
             include, but are not limited to the following:(A) Blood loss is known or suspected in
             a donor over 12 years of age, and the donor has received a transfusion or infusion of
             any of the following, alone or in combination:

               1. More than 2,000 milliliters (mL) of blood (e.g., whole blood, red blood cells) or
                  colloids within 48 hours before death or specimen collection, whichever occurred
                  earlier, or

               2. More than 2,000 mL of crystalloids within 1 hour before death or specimen
                  collection, whichever occurred earlier.
      
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:Recruiting
Lead Sponsor:John L. Reagan

Trial Keywords

  • Refractory
  • progression
  • recurrence

Last Updated

August 6, 2021