Acute Myeloid Leukemia
Conditions
Keywords
Refractory, progression, recurrence
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.
Interventions
Patients will be given gemtuzumab ozogamicin on days 1,4, and 7. Capped at 4.5mg individual doses. Total doses capped at 13.5mg.
OTHERDonor Leukocytes
The product will be administered unprocessed on day 8/24 hours post GO (same day as leukapheresis) with a minimum of CD3+ cells and maximum of CD3+ cells/kg irrespective of the number of CD34+ cells.
Sponsors
Brown University
Rhode Island Hospital
The Miriam Hospital
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Determine the RP2D or MTD of Nonengraftment Donor Leukocyte Infusions With Fractionated Gemtuzumab Ozogamicin in Patients With Relapsed/Refractory AML Defined as Dose Level Without Dose Limiting Toxicities. | 35 days post infusion | 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 | 4 weeks post infusion | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reaching 24 Months Progression Free Survival | Through 2 years post end of treatment | Progression free survival of infusional gemtuzumab ozogamicin followed by nonengraftment donor leukocyte infusions in patients with refractory acute myeloid leukemia. |
| Number of Participants Who Met the Objective for Overall Survival at 2 Years | Through 2 years post end of treatment | Overall survival of infusional gemtuzumab ozogamicin followed by nonengraftment donor leukocyte infusions in patients with refractory acute myeloid leukemia. |
| Number of Participants With Dose Limiting Toxicities as Defined by the Protocol | Start of treatment through 30 days post the final infusion | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJohn Reagan, MD
Brown University Oncology Research Group (BrUOG)
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age, Continuous | 68 years |
| Race and Ethnicity Not Collected | 0 Participants |
| Region of Enrollment United States | 11 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 3 | 4 / 4 | 4 / 4 |
| other Total, other adverse events | 3 / 3 | 4 / 4 | 3 / 4 |
| serious Total, serious adverse events | 3 / 3 | 2 / 4 | 3 / 4 |
Outcome results
None listed