Fractionated Gemtuzumab Ozogamicin Followed by Non-engraftment Donor Leukocyte Infusions for Relapsed/Refractory Acute Myeloid Leukemia
- Conditions
- Acute Myeloid Leukemia
- Interventions
- Drug: Gemtuzumab Ozogamicin (GO)Other: Donor Leukocytes
- Registration Number
- NCT03374332
- Lead Sponsor
- Brown University
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 11
Not provided
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Evidence of infection for HIV-1, HIV-2, syphilis, hepatitis B or C, HTLV 1 or 2, WNV, Chagas.
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Uncontrolled diabetes mellitus. If donor has controlled diabetes this must be documented by physician.
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Active or congestive heart failure syndrome from any cause per donor medical history. Approval for participation by Cardiologist required to be sent to BrUOG.
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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.
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Active angina pectoris. To be documented by physician
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Oxygen dependent pulmonary disease. To be documented by physician
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History of any lymphoid, myeloid or other non-solid malignancy. To be documented by physician
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Failure to receive full informed consent.
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Inadequate renal and/or hepatic function per medical history. To be documented by physician
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Known history of cirrhosis or active liver disease per medical history. To be documented by physician
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History of transplantation. To be documented by physician.
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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.
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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:
- 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
- More than 2,000 mL of crystalloids within 1 hour before death or specimen collection, whichever occurred earlier.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment 1: Gemtuzumab Ozogamicin and DLI Dose Level 1 Gemtuzumab Ozogamicin (GO) Patients ≥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. Treatment 1: Gemtuzumab Ozogamicin and DLI Dose Level 1 Donor Leukocytes Patients ≥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. Treatment 2: Gemtuzumab Ozogamicin and DLI Dose Level 2 Gemtuzumab Ozogamicin (GO) Patients ≥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. Treatment 2: Gemtuzumab Ozogamicin and DLI Dose Level 2 Donor Leukocytes Patients ≥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.
- Primary Outcome Measures
Name Time Method Response Rate Post infusion for a total of 2 years. 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
Name Time Method Survival Through 2 years post end of treatment Progression free survival and overall survival of infusional gemtuzumab ozogamicin followed by nonengraftment donor leukocyte infusions in patients with refractory acute myeloid leukemia.
Dose limiting toxicities Start of treatment through 30 days post the final infusion Rate of dose limiting toxicities of gemtuzumab ozogamicin followed by nonengraftment donor leukocyte infusions in patients with refractory acute myeloid leukemia.
Trial Locations
- Locations (1)
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States