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

NCT03374332

Last updated date
Study Location
Rhode Island Hospital
Providence, Rhode Island, 02903, United States
Contact
401-863-3000

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Acute Myeloid Leukemia
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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.

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Advanced Information
Descriptive Information
Brief Title  ICMJE Fractionated Gemtuzumab Ozogamicin Followed by Non-engraftment Donor Leukocyte Infusions for Relapsed/Refractory Acute Myeloid Leukemia
Official Title  ICMJE Fractionated Gemtuzumab Ozogamicin Followed by Non-engraftment Donor Leukocyte Infusions for Relapsed/Refractory Acute Myeloid Leukemia
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia
Intervention  ICMJE
  • Drug: Gemtuzumab Ozogamicin (GO)
    Patients will be given gemtuzumab ozogamicin on days 1,4, and 7. Capped at 4.5mg individual doses. Total doses capped at 13.5mg.
    Other Name: Mylotarg
  • Other: Donor 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.
Study Arms  ICMJE
  • Experimental: Treatment 1: Gemtuzumab Ozogamicin and DLI Dose Level 1

    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.

    Interventions:
    • Drug: Gemtuzumab Ozogamicin (GO)
    • Other: Donor Leukocytes
  • Experimental: Treatment 2: Gemtuzumab Ozogamicin and DLI Dose Level 2

    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.

    Interventions:
    • Drug: Gemtuzumab Ozogamicin (GO)
    • Other: Donor Leukocytes
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 13, 2017)
18
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2022
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Roxanne Wood, BA, CCRC401-863-3000[email protected]
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03374332
Other Study ID Numbers  ICMJE BrUOG 345
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party John Reagan, Brown University
Study Sponsor  ICMJE John Reagan
Collaborators  ICMJE
  • Brown University
  • Rhode Island Hospital
  • The Miriam Hospital
  • Pfizer
Investigators  ICMJE
Principal Investigator:John Reagan, MDBrown University Oncology Research Group (BrUOG)
PRS Account Brown University
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP