再発/難治性急性骨髄性白血病に対する分画ゲムツズマブオゾガマイシンとその後の非生着ドナー白血球注入

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.

• マイロターグ

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.

• マイロターグ

Maximum Tolerated Dose (MTD) determined from Phase 1 portion of study

Day 8: The product will be administered unprocessed on day 8 (same day as leukapheresis) with a dose of 1x10^7 - 2x10^7 CD3+ cells OR 1x10^8 - 2x10^8 CD3+ cells/kg irrespective of the number of CD34+ cells. MTD AS DETERMINED BY PHASE 1

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.

• マイロターグ

The MTD of non-engraftment donor leukocyte infusions administered with fractionated gemtuzumab ozogamicin in patients with relapsed/refractory AML is determined by the dose level achieved with no Dose limiting toxicities. Measure = participants without DLTs.

The recommended phase 2 dose (RP2D) or maximum tolerated dose (MTD) was evaluated by utilizing a 3+3 design to determine if 1-2x108 CD3 cells/kg can be safely administered with fractionated Gemtuzumab Ozogamicin administered on days 1,4 and 7 (total dose capped at 13.5 mg). The leukocyte infusion is administered on day 8 after completion of GO day 7.

Two DLI dose levels well be assessed:

DLI Dose Level 1: 1-2x107 CD3+ cells/kg DLI Dose Level 2: 1-2x108 CD3+ cells/kg The RP2D/MTD is determined by the dose level achieved with no Dose limiting toxicities. Measure = participants without DLTs through 35 days post DLI.

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.

Complete remission or complete remission with incomplete count recovery, after one cycle of treatment. Rationale for including CRi: CRi has previously been used in gemtuzumab ozogamicin trials because of incomplete platelet recovery seen with this drug.

Number of participants with dose limiting toxicities following treatment with gemtuzumab ozogamicin followed by nonengraftment donor leukocyte infusions in patients with refractory acute myeloid leukemia. DLT's defined in the protocol as

• IBMTR Severity Index C & D graft versus host disease
• Grade 3 or 4 infusion related reaction
• Any grade 3 non-hematological toxicities not directly resulting from patient's disease (with some exclusions specified in the protocol)
• Any grade 4 related or unrelated non-hematological toxicity not directly resulting from patient's disease
• Development of SOS
• Discontinuation of treatment due to an adverse event of any grade is considered a DLT unless the AE is clearly and solely related to the underlying disease.

All Grade 5 toxicities are considered DLTs unless clearly and solely related to the underlying disease.