Last updated on December 2018

A Phase I Study of Lintuzumab-Ac225 in Patients With Refractory Multiple Myeloma

Brief description of study

  1. Establish the MTD of fractionated doses of Lintuzumab-Ac225 as monotherapy
  2. Establish overall response rate (ORR) where ORR = CR + sCR+ VGPR+PR)
  3. Confirm the safety profile of the treatment regimen
  4. Determine changes in plasmocyte, T-cell and MDSC cell populations
  5. Estimate progression-free survival (PFS) and overall survival

Detailed Study Description

The study is a multicenter, open label Phase I trial. Phase 1, dose-escalation : This study uses a 3+3 design to estimate the maximum tolerated dose (MTD).

There will be 2 escalating dose levels in the trial (0.5 Ci/kg and 1 Ci/kg,). Each dose can be administered in up to 4-8 cycles providing that the total dose received per patient does not exceed 4 Ci/kg.

De-escalation (decrease dose level to 0.25 Ci/kg) is planned if at the first dose level of 0.5 Ci/kg, after expanding the cohort to a maximum of 6 patients, 1/3 patients have M protein decrease >10% AND 2 patient have DLTs. At the dose level of 0.25 Ci/kg, if eligible to continue receiving additional doses of the study drug, patients will receive up to 8 doses in total, with the total administered activity being 2 Ci/kg.

The starting dose level will be 0.5 Ci/kg of 225Ac-Lintuzumab administered on day 1 of each cycle. If this dose level is safe, the second dose level of 1 Ci/kg will be explored. If the starting dose level results in DLTs in 2 patients and 1/3 patients have M protein decrease >10%, the dose level of 0.25 Ci/kg will be explored.

Subjects will receive the investigational drug as a single infusion at the prescribed dose level.

Intra cohort dose escalation/ decrease is not allowed.

Minimum three to maximum six patients will be treated at each dose level, and dose escalation will proceed as follows:

  1. if 1/3 patients have M protein decrease >10% on Day 42 AND no patients have DLTs, redose at the same dose level by Day 60 if ANC and PLT counts allow;
  2. if 1 patient at the given dose level has DLTs, expand the cohort by adding 3 more patients at that dose level.
  3. if 1/3 of patients in the expanded cohort exhibit DLTs, proceed to the next dose level.
  4. if at the first dose level,after expanding the cohort to a maximum of 6 patients .1/3 patients have M protein decrease >10% AND .2 patient has DLTs, decrease dose level to 0.25 uCi/kg
  5. if no patients at the reduced dose level of 0.25 uCi/kg have M protein decrease >10% AND 1 patient has DLTs terminate trial
  6. if none of the patients have DLTs at the given dose level, escalate to the next dose level.
  7. if 2 or more patient exhibit DLTs at any given dose level, the previous dose level will be considered MTD.
  8. if 2/3 patients respond with PR or better and <1/3 patients have DLTs, complete Phase 1 portion at that dose level (no further dose escalation).
  9. if patients who have at least stable disease are eligible to receive an additional cycle of treatment by Day 60 and their response status remains worse than CR, they will continue receiving repeated doses of study drug every 60 days after cycle 2 until they have received a cumulative dose of up to 4 Ci/kg or until they achieve CR, whichever is sooner.

All patients will receive GCSF support starting on Day 9 and continuing until ANC>1,000.

After the dose escalation portion is completed, treat 3 additional patients at the highest established dose level to confirm MTD and establish that dose level as MTD.

Clinical Study Identifier: NCT02998047

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