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

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ClinicalTrials.gov Identifier: NCT03374332
Recruitment Status : Not yet recruiting
First Posted : December 15, 2017
Last Update Posted : April 20, 2018
Sponsor:
Collaborators:
Brown University Oncology Research Group
Rhode Island Hospital
The Miriam Hospital
Pfizer
Information provided by (Responsible Party):
John Reagan, 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.


Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: Gemtuzumab Ozogamicin (GO) Other: Donor Leukocytes Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prolonged Fractionated Gemtuzumab Ozogamicin Followed by Non-engraftment Donor Leukocyte Infusions for Relapsed/Refractory Acute Myeloid Leukemia
Estimated Study Start Date : June 2018
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2022


Arm Intervention/treatment
Experimental: Treatment 1: Gemtuzumab Ozogamicin and DLI >or =70 years old

Patients > 70 years of age will be given gemtuzumab ozogamicin 6mg/m2 (2mg/m2 each day, capped at 4.5mg) from Day 1, 4, 7.

Day 8: The product will be administered unprocessed on day 8 (same day as leukapheresis) with a minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg irrespective of the number of CD34+ cells.

Drug: Gemtuzumab Ozogamicin (GO)

Treatment 1: > or = 70 years old: GO 6mg/m2 (2mg/m2 each dose, capped at 4.5mg)

Treatment 1: < 70 years old: GO 9mg/m2 (3mg/m2 each dose, capped at 4.5mg)

Treatments 2 and 3: 6mg/m2 (2mg/m2 each dose, capped at 4.5mg)

Day 1,4,7

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 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg irrespective of the number of CD34+ cells.

Experimental: Treatment 1 : Gemtuzumab Ozogamicin and DLI < 70 years old

Patients > 70 years of age will be given gemtuzumab ozogamicin 9mg/m2 (3mg/m2 each day,capped at 4.5mg) from Day 1, day 4, day 7

Day 8: The product will be administered unprocessed on day 8 (same day as leukapheresis) with a minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg irrespective of the number of CD34+ cells.

Drug: Gemtuzumab Ozogamicin (GO)

Treatment 1: > or = 70 years old: GO 6mg/m2 (2mg/m2 each dose, capped at 4.5mg)

Treatment 1: < 70 years old: GO 9mg/m2 (3mg/m2 each dose, capped at 4.5mg)

Treatments 2 and 3: 6mg/m2 (2mg/m2 each dose, capped at 4.5mg)

Day 1,4,7

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 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg irrespective of the number of CD34+ cells.

Experimental: Treatment #2: Gemtuzumab Ozogamicin and DLI

Patients who show a transient response to therapy can receive up to two additional donor leukocyte infusions with GO 6mg/m2 (2mg/m2 day,capped at 4.5mg) for all patients regardless of age administered day 1, 4, 7, no sooner than 35 days status post their last cellular infusion.

Day 8: The product will be administered unprocessed on day 8 (same day as leukapheresis) with a minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg irrespective of the number of CD34+ cells.

Drug: Gemtuzumab Ozogamicin (GO)

Treatment 1: > or = 70 years old: GO 6mg/m2 (2mg/m2 each dose, capped at 4.5mg)

Treatment 1: < 70 years old: GO 9mg/m2 (3mg/m2 each dose, capped at 4.5mg)

Treatments 2 and 3: 6mg/m2 (2mg/m2 each dose, capped at 4.5mg)

Day 1,4,7

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 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg irrespective of the number of CD34+ cells.

Experimental: Treatment #3: Gemtuzumab Ozogamicin and DLI

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 day 1,4,7, no sooner than 35 days status post their last cellular infusion.

Day 8: The product will be administered unprocessed on day 8 (same day as leukapheresis) with a minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg irrespective of the number of CD34+ cells.

Drug: Gemtuzumab Ozogamicin (GO)

Treatment 1: > or = 70 years old: GO 6mg/m2 (2mg/m2 each dose, capped at 4.5mg)

Treatment 1: < 70 years old: GO 9mg/m2 (3mg/m2 each dose, capped at 4.5mg)

Treatments 2 and 3: 6mg/m2 (2mg/m2 each dose, capped at 4.5mg)

Day 1,4,7

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 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg irrespective of the number of CD34+ cells.




Primary Outcome Measures :
  1. Response Rate [ Time Frame: 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 :
  1. Survival [ Time Frame: 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.

  2. Dose limiting toxicities [ Time Frame: Start of treatment through 16 weeks 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 < 2 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:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03374332


Contacts
Contact: Kayla Rosati, EdM 401-863-3000 kayla_rosati@brown.edu

Locations
United States, Rhode Island
Rhode Island Hospital Not yet recruiting
Providence, Rhode Island, United States, 02903
Contact: Kayla Rosati, EdM    401-863-3000    kayla_rosati@brown.edu   
Principal Investigator: John Reagan, MD         
Sponsors and Collaborators
John Reagan
Brown University Oncology Research Group
Rhode Island Hospital
The Miriam Hospital
Pfizer
Investigators
Principal Investigator: John Reagan, MD Brown University Oncology Research Group (BrUOG)

Responsible Party: John Reagan, Principal Investigator: Sponsor-Investigator, Brown University
ClinicalTrials.gov Identifier: NCT03374332     History of Changes
Other Study ID Numbers: BrUOG 345
First Posted: December 15, 2017    Key Record Dates
Last Update Posted: April 20, 2018
Last Verified: April 2018

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

Keywords provided by John Reagan, Brown University:
Refractory
progression
recurrence

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Gemtuzumab
Antineoplastic Agents