Acute Myeloid Leukemia Clinical Trial

IMGN632 as Monotherapy or With Venetoclax and/or Azacitidine for Participants With CD123-Positive Acute Myeloid Leukemia

Summary

This is an open-label, multicenter, Phase 1b/2 study to determine the safety and tolerability of IMGN632 and assess the antileukemia activity of IMGN632 when administered in combination with azacitidine and/or venetoclax in patients with relapsed and frontline CD123-positive AML, and antileukemia activity of IMGN632 when administered as monotherapy in patients with MRD+ AML after frontline treatment.

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Full Description

This study explores multiple IMGN632 doses in combination and monotherapy Regimens, including (A - closed to enrollment)) azacitidine, (B-closed to enrollment) venetoclax, (C) azacitidine+venetoclax, and (D- closed to enrollment) monotherapy in MRD+ AML. For combination Regimens A-C, a Phase 1b Dose Escalation Cohort will determine the recommended Phase 2 dose (RP2D) of IMGN632 in that specific combination Regimen, followed by a Phase 2 Dose Expansion Cohort for each combination Regimen to characterize the safety profile further and assess the antileukemia activity of the different combination Regimens.

View Eligibility Criteria

Eligibility Criteria

Patient Inclusion Criteria

Patient must be ≥ 18 years of age.
Patients must have confirmed diagnosis of AML (excluding acute promyelocytic leukemia) based on World Health Organization classification (Arber 2016).

Disease characteristics and allowable prior therapy:

Patients must be evaluated for any available standard of care therapies (including induction, consolidation chemotherapy and/or transplant) and, in the opinion of the treating physician, be deemed appropriate for this experimental therapy.
Treatment-naïve (untreated) patients will be allowed in the Expansion Phase for Regimen C (Triplet) (IMGN632 + azacitidine + venetoclax). No prior treatments with hypomethylating agents (HMAs) for MDS are allowed.
Patients must have CD123-positive AML as confirmed by local flow cytometry (or immunohistochemistry [IHC]).
Patients may have received prior CD123-targeted therapies, except IMGN632, as long as CD123 remains detectable during screening.
Relapsed or refractory CD123-positive AML patients will be allowed to enroll in the Escalation Phase of Regimens A, B, and C (Triplet) (IMGN632 + azacitidine, venetoclax, or azacitidine + venetoclax, respectively) and relapsed CD123-positive AML patients will be allowed to enroll the Expansion Phase of Regimens A-C. Note: Patients may also have received up to 2 prior lines of therapy, eg, frontline treatment (induction, consolidation [including transplant], and maintenance) and 1 salvage regimen.
Patients enrolling in Regimen D must be in CR (CR/CRh/CRp/CRi) and be MRD+ at the time of screening, confirmed by central laboratory testing. Patients may have no more than 2 prior lines of therapy (which may include stem cell transplant), ie, frontline or first salvage. Note: Fit patients who received intensive treatment (eg 3+7, HiDAC) are eligible for Regimen D Cohort D1. Unfit patients who received non-intensive treatment (eg, HMA, low dose cytarabine) are eligible for Regimen D Cohort D2.
Previous treatment-related toxicities must have resolved to Grade 1 or baseline (excluding alopecia).
For patients enrolling in Regimens A-D, total WBC count must < 25 × 10^9 cells/L. Hydroxyurea may be used to control blood counts before Cycle 1 Day 1, at the discretion of the treating physician, according to institutional practice. During the Escalation Phase in Regimens A-C, hydroxyurea may also be used during Cycle 1.
Liver enzymes (AST and ALT) ≤ 3 × the upper limit of normal (ULN).
Total bilirubin ≤ 1.5 × the ULN; patients with Gilbert syndrome must have total bilirubin < 3.0 × ULN with direct bilirubin < 1.0 × ULN at the time of enrollment.
An estimated glomerular filtration rate (eGFR) of > 30 mL/min/1.73 m2 or creatinine clearance of > 30 mL/min.
Left ventricular ejection fraction (LVEF) ≥ 45% for patients enrolling in Regimens A-D based on locally available assessment, eg, echocardiogram or other modality.
Patients with prior autologous or allogeneic bone marrow transplant are eligible. Patients with an allogeneic transplant must meet the following conditions: The transplant must have been performed more than 120 days before the date of dosing on this study, the patient must not have active ≥ Grade 2 graft versus host disease (GvHD), or extensive chronic GvHD of any severity, and must be off all immunosuppression for at least 2 weeks prior to first dose of IMGN632.
Voluntary written informed consent before performance of any study-related procedure not part of normal medical care.
Women of childbearing potential (WCBP), defined as sexually mature women who have not undergone surgical sterilization or who have not been naturally postmenopausal for at least 12 consecutive months (ie, who have had menses any time in the preceding 12 consecutive months), must agree to use acceptable contraceptive methods while on study drug and for at least 7 months after the last dose of IMGN632.
WCBP must have a negative pregnancy test within 3 days before the first dose of study drug.
Male patients who are able to father children must agree to use acceptable methods of contraception throughout the study and for at least 4 months after the last dose of study drug(s).
Patients with prior malignancy are eligible; however, the patient's malignancy must be well-controlled or stable and have completed all systemic chemotherapy and radiotherapy for the prior malignancy at least 6 months before enrollment, and all treatment-related toxicities must have resolved to ≤ Grade 1 (excluding alopecia). Note: patients with prostate cancer or breast cancer on adjuvant hormonal therapy are eligible and may or may not be on long-term maintenance treatment that is unlikely to interfere with study therapy. Note: patients with tumors with a negligible risk for metastasis or death (eg, adequately controlled basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast) are eligible.

Patients in expansion Cohorts C1 and C2 must be considered ineligible for intensive induction therapy defined by the following:

≥ 75 years of age OR
< 75 years of age with at least one of the following co-morbidities documented within 28 days of Cycle 1 Day 1:
ECOG performance status of 2 or 3
History of congestive heart failure requirement treatment or ejection fraction ≤ 50% or chronic stable angina
Diffusing capacity of the lung for carbon monoxide ≤ 65% or forced expiratory volume in 1 second ≤ 65%
Creatinine clearance ≥ 30 mL/min to < 45 mL/min
Moderate hepatic impairment with total bilirubin > 1.5 to ≤ 3.0 × ULN
Patients in Cohort C1 and C2 must have an ECOG performance status of 0 to 2 for those ≥ 75 years of age OR 0 to 3 for < 75 years of age.

Patient Exclusion Criteria

Patients who have received any anticancer therapy, including investigational agents, within 14 days (or within 28 days for checkpoint inhibitors) before drug administration on this study (hydroxyurea is allowed before beginning study treatment). Patients must have recovered to baseline from all acute toxicity from this prior therapy.
Patients who have been previously treated with IMGN632.
Patients with myeloproliferative neoplasm-related secondary AML are excluded from the Dose Expansion Phase of the study.
Patients with active central nervous system (CNS) AML will be excluded. A lumbar puncture does not need to be performed unless there is clinical suspicion of CNS involvement per investigator judgement. Concurrent therapy for CNS prophylaxis or continuation of therapy for controlled CNS AML is allowed with the approval of the sponsor.
Patients with a history of sinusoidal obstruction syndrome/venous occlusive disease of the liver.
Myocardial infarction within 6 months before enrollment or New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities before study entry.
Clinically relevant active infection including known active hepatitis B or C, HIV infection, or cytomegalovirus or any other known concurrent infectious disease that, in the judgment of the investigator, would make a patient inappropriate for enrollment into this study (testing not required).
Patients who have undergone a major surgery within 4 weeks (or longer if not fully recovered) before study enrollment.
Serious or poorly controlled medical conditions that could be exacerbated by treatment or that would seriously compromise safety assessment or compliance with the protocol, in the judgment of the investigator.
Women who are pregnant or breastfeeding
Prior known hypersensitivity reactions to monoclonal antibodies (≥ Grade 3).
Prior known hypersensitivity reactions to study drugs and/or any of their excipients.
Patients who have a history of allergy to IMGN632 (or any of its excipients), azacitidine, or venetoclax.

Study is for people with:

Acute Myeloid Leukemia

Phase:

Phase 1

Estimated Enrollment:

292

Study ID:

NCT04086264

Recruitment Status:

Recruiting

Sponsor:

ImmunoGen, Inc.

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There are 28 Locations for this study

See Locations Near You

City of Hope Comprehensive Cancer Center
Duarte California, 91010, United States More Info
Ahmed Aribi, MD
Contact
626-218-1133
[email protected]
Contact
877-467-3411
Ahmed Aribi, MD
Principal Investigator
UC Irvine Medical Center
Orange California, 92868, United States More Info
Veronica de Santiago
Contact
877-827-8839
[email protected]
Deepa Jeyakumar, MD
Principal Investigator
Moffitt Cancer Center
Tampa Florida, 33612, United States More Info
Caroline Wagstaff
Contact
813-745-5197
[email protected]
David Sallman, MD
Principal Investigator
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago Illinois, 60611, United States More Info
Patrick McNamara
Contact
312-695-0267
[email protected]
Jessica Altman, MD
Principal Investigator
Beth Israel Deaconess Medical Center
Boston Massachusetts, 02215, United States More Info
Jessica Liegel, MD
Contact
617-667-9920
[email protected]
Jessica Liegel, MD
Principal Investigator
Dana-Farber Cancer Institute
Boston Massachusetts, 02215, United States More Info
Ashleigh Burroughs
Contact
617-632-3500
[email protected]
Daniel DeAngelo, MD
Principal Investigator
University of Michigan Hospital
Ann Arbor Michigan, 48109, United States More Info
Cancer Answer Line
Contact
800-865-1125
[email protected]
Patrick Burke, Dr.
Principal Investigator
Mayo Clinic Hospital - Rochester St. Mary's Campus
Rochester Minnesota, 55905, United States More Info
Clinical Trials
Contact
855-776-0015
[email protected]
Kebede Benga, Dr.
Principal Investigator
Roswell Park Comprehensive Cancer Center
Buffalo New York, 14203, United States More Info
Emily Li
Contact
716-845-4176
Eunice Wang, MD
Principal Investigator
NewYork-Presbyterian - Weill Cornell
New York New York, 10021, United States More Info
Tania J Curcio
Contact
212-746-2571
[email protected]
Gail Roboz, MD
Principal Investigator
Duke University Health System
Durham North Carolina, 27710, United States
Cleveland Clinic
Cleveland Ohio, 44195, United States More Info
Lauren Lee
Contact
216-636-9369
[email protected]
Anjali Advani, MD
Principal Investigator
MD Anderson
Houston Texas, 77030, United States More Info
Joie Alvarez
Contact
713-792-7321
[email protected]
Naval Daver, MD
Principal Investigator
Fred Hutchinson Cancer Research Center
Seattle Washington, 98109, United States More Info
Cherise Athay
Contact
206-667-4536
[email protected]
Roland Walter, MD
Principal Investigator
Hospices Civils de Lyon, Lyon-Sud Hospital
Lyon , 69495, France More Info
Maël Heiblig
Contact
33478862235
[email protected]
Maël Heiblig, Dr.
Principal Investigator
Institute Paoli-Calmettes
Marseille , 13009, France More Info
Sylvain Garciaz, MD
Contact
0033491223868
[email protected]
Sylvain Garciaz, Dr.
Principal Investigator
Centre Antoine Lacassagne
Nice , 06100, France More Info
Lauris Gastaud, MD
Contact
+ 33 (0) 492031221
[email protected]
Lauris Gastaud, MD
Principal Investigator
Hôspital Saint-Louis
Paris , 75010, France More Info
Nicholas Boissel, D=MD
Contact
+33 142499643
[email protected]
Nicholas Boissel, Dr.
Principal Investigator
CHU de Toulouse
Toulouse , 31059, France More Info
Christian Recher, MD
Contact
0033 05 82741631
[email protected]
Christian Recher, Dr.
Principal Investigator
Hôpital André Mignot
Versailles , 78157, France More Info
Philippe Rousselot, MD
Contact
0033 01 39638010
[email protected]
Philippe Rousselot, MD
Principal Investigator
University Hospital Leipzig
Leipzig , 04103, Germany More Info
Karolin Hubert
Contact
+49 341 97-20363
[email protected]
Jana Heinrichs-Knopf
Contact
+49 341 97 12634
Uwe Platzbecker, MD
Principal Investigator
Sabine Kayser, MD
Sub-Investigator
University Hospital Muenster
Münster , 48149, Germany More Info
Christopher Schliemann, MD
Contact
0049 251 83 45363
[email protected]
Christopher Schliemann, Dr.
Principal Investigator
University Hospital of Ulm
Ulm , 89081, Germany More Info
Ayten Sagir
Contact
0731-45927
[email protected]
Tobias Glöggler
Contact
0731-45746
[email protected]
Silke Kapp-Schwoerer, Dr
Principal Investigator
Frank Rueker, Dr
Sub-Investigator
Istituto di Ematologia "Lorenzo e A. Seragnoli" - Policlinco S. Orsola - Malpighi
Bologna , 40138, Italy More Info
Antonio Curti, MD
Contact
+390512144074
[email protected]
Antonio Curti, MD
Principal Investigator
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)
Meldola , 47014, Italy More Info
Giovanni Marconi, MD
Contact
0039 0543 739292
[email protected]
Giovanni Martinelli, MD
Principal Investigator
European Institute of Oncology IRCCS
Milano , 20141, Italy More Info
Enrico Derenzini, MD
Contact
+39 0257489.538
[email protected]
Enrico Derenzini, Dr.
Principal Investigator
Azienda Ospedaliera Universitaria Maggiore Della Carita Novara
Novara , 28100, Italy More Info
Monica Lunghi, MD
Contact
+39 0321 3733092
[email protected]
Monica Lunghi, MD
Principal Investigator
MD Anderson Cancer Center Madrid, Spain
Madrid , , Spain More Info
Adolfo de La Fuente, MD
Contact
+34917878600
[email protected]
Adolfo de La Fuente, MD
Principal Investigator
Hospital Universitario y Politécnico de La Fe
Valencia , 46026, Spain More Info
David Pellicer
Contact
0034961244864
[email protected]
Pau Montesinos, MD
Principal Investigator
Oxford University Hospital - Churchill Hospital
Headington , OX3 7, United Kingdom More Info
Paresh Vyas, MD
Contact
0044 01865222443
[email protected]
Paresh Vyas, Dr.
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Acute Myeloid Leukemia

Phase:

Phase 1

Estimated Enrollment:

292

Study ID:

NCT04086264

Recruitment Status:

Recruiting

Sponsor:


ImmunoGen, Inc.

How clear is this clinincal trial information?

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