Iberdomide and Daratumumab as Maintenance Therapy After an Autologous Stem Cell Transplant for Multiple Myeloma

Study Purpose

The goal of this phase 2 clinical trial is to learn if patients with Multiple Myeloma who are minimal residual disease positive after initial therapy (including an autologous stem cell transplant [ASCT]) will benefit from maintenance therapy with Iberdomide and subcutaneous (SC) Daratumumab. The main questions it aims to answer are:

  • - Assess if giving Iberdomide and the SC Daratumumab in the maintenance setting is an effective treatment and warrants further investigation in patients with residual disease.
  • - Is giving Iberdomide and SC Daratumumab maintenance post ASCT a safe option.
Participants will:
  • - provide informed consent and complete screening assessments for eligibility within 28 days of starting treatment.
  • - Screening assessments include specific laboratory tests, a medical history assessment and a physical examination (including temperature, pulse, blood pressure, respirations, height and weight), an assessment of your heart function, a breathing test, cancer imaging, a bone marrow biopsy, minimal residual disease testing (MRD) and a questionnaire.
  • - If eligible, patients will start treatment with Iberdomide (1.0 mg on day 1-21 of each 28 day cycle, with an increase to 1.3 mg on Cycle 4 if the 1.0 mg dose was tolerated, to a maximum of 26 cycles or progressive disease, whichever is first) and SC Daratumumab (1800 mg SC on days 1, 8, 15 and 22 of cycle 1 and 2, then 1800 mg SC on Day 1 and 15 of cycle 3-6 and 1800 mg SC on Day 1 for cycles 7-26 to a maximum of 26 cycles or progressive disease, whichever is first) - while receiving treatment on study, physical exams (including temperature, pulse, blood pressure, respirations, height and weight), toxicity assessments, laboratory assessments and questionnaires will be done at various times over the course of the 26 cycles.
  • - an MRD assessment is required at 6, 12 and 24 months after starting treatment.
  • - End of treatment will occur once 26 cycles are completed, or cancer has progressed whichever comes first.
At that time, specific laboratory tests, a physical examination (including temperature, pulse, blood pressure, respirations, height and weight), cancer imaging, a bone marrow biopsy and minimal residual disease testing (MRD) will occur.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Multiple Myeloma patients who have received prior DARA-containing induction therapy and have attained at least a partial response. 2. Patients who have completed Autologous Stem Cell Transplant (ASCT) 90-150 days prior to registration, without any post-ASCT therapy and without post-ASCT disease progression (according to IMWG criteria) 3. Patients who are Minimal Residual Disease positive (MRD (+)) as measured by the ClonoSEQ assay using a sensitivity of 10-5, measured 90-150 days following ASCT. 4. Prior DARA-containing induction therapy (at least 3 cycles), attaining at least a partial response. 5. Completed ASCT within 90-150 days prior to registration, without any post-ASCT therapy and without evidence of post-ASCT disease progression (according to IMWG criteria) 6. MRD (+) at the time of study enrollment using the clonoSEQ NGS (next-generation sequencing) assay. Patients with an M-spike of ≥ 0.5 g/dL and/or an abnormal free light chain ratio (with an involved serum free light chain of ≥ 10 mg/dL) at enrollment are considered MRD (+) and do not require baseline MRD testing if they have previously had this testing done with successful clonality assessment. 7. ECOG (Eastern Cooperative Oncology Group) Performance Status /= 75,000/mm3, hemoglobin >/= 8 g/dL, and ANC (absolute neutrophil count) >/= 1,000/mm3 within 28 days prior to registration. NOTE: transfusion to achieve the hemoglobin threshold IS permissible. 9. Adequate hepatic function defined by the following within 28 days prior to registration: total bilirubin /= 30 mL/min., as measured by a 24-hour urine collection or estimated by the Cockcroft and Gault formula within 28 days prior to registration. 11. All ASCT-related toxicities must have recovered to Exclusion Criteria: 1. Active HIV, or HCV (defined as detectable viremia for any of these conditions). 2. Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen[HBsAg]). Patients with resolved infection (i.e., patients who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time PCR (polymerase chain reaction) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Patients with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR. 3. Unable to assess MRD status at entry or is MRD(-) at 10-5 threshold at entry. 4. Heart attack or stroke within 90 days of study enrollment. 5. Unable to tolerate required anti-thrombotic or anti-viral prophylaxis. 6. Major surgery within 28 days of enrollment. 7. Medical, neurologic, or psychiatric condition which renders patient unable to safely comply with study therapy and schedule requirements (including, but not limited to, unstable angina, New York Heart Association Class III-IV congestive heart failure, or uncontrolled cardiac arrhythmia) 8. Intolerance of prior DARA therapy (requiring discontinuation of DARA previously due to toxicity) 9. A history of malignancy (other than multiple myeloma) unless all treatment of that malignancy was completed at least 2 years before consent and the patient has no evidence of disease before the date of enrollment. Exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years. 10. Be exhibiting clinical signs of meningeal or central nervous system involvement due to multiple myeloma. 11. Have known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal. 12. Have known moderate or severe persistent asthma within the past 2 years (see Section 9.2.4), or current uncontrolled asthma of any classification. Note that patients who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study, provided that FEV1 is ≥50% of predicted normal. Note: pursuant to exclusion criteria (k) and (l), FEV1 testing is required for patients with suspected COPD or asthma. Patients with FEV1 <50% of predicted normal (or for patients ≥65 years of age, old FEV1 <50% or diffusing capacity of the lung [DLCO] <50%) on screening assessment must be excluded. 13. Have any of the following: 1. Myocardial infarction within 6 months of enrollment, or an unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV), 2. Uncontrolled cardiac arrhythmia. 14. Have known allergies, hypersensitivity, or intolerance to boron or mannitol, sorbitol, corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to the IB) or known sensitivity to lenalidomide, thalidomide, or pomalidomide. 15. Be pregnant, or breast-feeding, or planning to become pregnant or breast-feed while enrolled in this study or within 90 days after the last dose of study treatment(s). Or, if male, planning to father a child while enrolled in this study or within 90 days after the last dose of study treatment(s). 16. Prolongation of QT interval on screening ECG as defined by a QTc interval > 470 msec using Fridericia's QT correction formula. 17. Use of strong inhibitors or inducers of CYP3A4, P-gp, or BCRP for at least 14 days or 5 half-lives (whichever is shorter) prior to initiating protocol therapy.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT06107738
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Barbara Ann Karmanos Cancer Institute
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Jeffery Zonder, M.D.
Principal Investigator Affiliation Barbara Ann Karmanos Cancer Institute
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, Industry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Multiple Myeloma
Arms & Interventions

Arms

Experimental: Iberdomide and Daratumumab

Interventions

Drug: - Iberdomide

Iberdomide 1.0mg daily for days 1-21 of a 28-day cycle, an increase to 1.3 mg daily on Day 1-21 of a 28-day cycle is allowed at cycle 4 or higher if the 1.0 mg dose was well tolerated.

Drug: - Daratumumab/rHuPH20 Co-formulation

Daratumumab/rHuPH20 will be dosed as follows: Daratumumab/rHuPH20 1800 mg SC days 1, 8, 15, 22 (28-day cycle; cycles 1-2) Daratumumab/rHuPH20 1800 mg SC days 1, 15 (28-day cycle; cycles 3-6) Daratumumab/rHuPH20 1800 mg SC day 1 (28-day cycle; cycles 7-26)

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Karmanos Cancer Institute, Detroit, Michigan

Status

Recruiting

Address

Karmanos Cancer Institute

Detroit, Michigan, 48201

Site Contact

Christiane Houde

Houdec@karmanos.org

313-576-8673