Venetoclax-Dexamethasone in Relapsed and/or Refractory t(11;14) Amyloidosis

Browse trials for

• Immunoglobulin Light-chain Amyloidosis 167

Keywords

• Light Chain Amyloidosis
• Protein Misfolding Disorder

Immunoglobulin Light-chain Amyloidosis

167 studies on the registry are indexed under Immunoglobulin Light-chain Amyloidosis; 57 are open to participants now.

This study's planned enrollment of 53 is above the median of 37 across 120 interventional studies indexed under Immunoglobulin Light-chain Amyloidosis.

Lead sponsor

Columbia University is the lead sponsor of 1,103 studies on the registry; 193 are open to participants now.

Of its 172 completed or terminated interventional studies of FDA-regulated products, 142 (83%) have results posted.

Study arms

• Experimental
  Phase 1: Venetoclax 200 mg

  Cohort 1: Venetoclax 200 mg tablet, once daily for up to 2 cycles after achieving best response, for a maximum of 6 cycles (1 cycle = 28 days)

  Drug: Venetoclax Oral Tablet, 200 mg · Device: FISH assay

• Experimental
  Phase 1: Venetoclax 400mg

  Cohort 2: Venetoclax 400 mg tablet, once daily for up to 2 cycles after achieving best response, for a maximum of 6 cycles (1 cycle = 28 days)

  Device: FISH assay · Drug: Venetoclax Oral Tablet, 400 mg

• Experimental
  Phase 1: Venetoclax 400mg + Dexamethasone 10 mg

  Cohort 3: Venetoclax 400 mg tablet, once daily and Dexamethasone 10 mg tablet once weekly, for up to 2 cycles after achieving best response, for a maximum of 6 cycles (1 cycle = 28 days)

  Device: FISH assay · Drug: Venetoclax Oral Tablet, 400 mg · Drug: Dexamethasone Oral, 10 mg

• Experimental
  Phase 1: Venetoclax 400mg + Dexamethasone 20 mg

  Cohort 4: Venetoclax 400 mg tablet, once daily and Dexamethasone 20 mg tablet once weekly, for up to 2 cycles after achieving best response, for a maximum of 6 cycles (1 cycle = 28 days)

  Device: FISH assay · Drug: Venetoclax Oral Tablet, 400 mg · Drug: Dexamethasone Oral, 20 mg

• Experimental
  Phase 2: Venetoclax MTD with Dexamethasone

  Venetoclax MTD (200 mg or 400 mg) with Dexamethasone (10 mg or 20 mg) as determined by the phase I results

  Drug: Venetoclax MTD with Dexamethasone

• Active comparator
  Phase 2: Control Arm (Investigator's Choice)

  Participants will receive one of the following as determined by the investigator: Daratumumab, Pomalidomide, Bendamustine, or Ixazomib (+/- dexamethasone)

  Drug: Dexamethasone Oral, 20 mg · Drug: Daratumumab Injection · Drug: Bendamustine · Drug: Pomalidomide · Drug: Ixazomib

Interventions

• DrugVenetoclax Oral Tablet, 200 mg

  200 mg oral tablet daily

  Also known as: Venclexta

• DeviceFISH assay

  Cytogenetic analysis is intended for evaluation of relapsed/refractory AL amyloidosis using fluorescence in situ hybridization (FISH) using known translocation probes. Bone marrow aspirate (BMA) samples are collected in lavender top (Ethylenediaminetetraacetic acid (EDTA)) or green top (Sodium heparin) tubes. Specimen tubes shall be transported at room temperature to the laboratory on the same day of collection.

  Also known as: t(11;14) FISH assay

• DrugVenetoclax Oral Tablet, 400 mg

  400 mg oral tablet daily

  Also known as: Venclexta

• DrugDexamethasone Oral, 10 mg

  10 mg oral tablet weekly

  Also known as: Decadron, Hemady

• DrugDexamethasone Oral, 20 mg

  20 mg oral tablet weekly

  Also known as: Decadron, Hemady

• DrugDaratumumab Injection

  Daratumumab will be administered at a dose of 16 mg/kg by IV infusion once weekly for weeks 1 to 8, every 2 weeks for weeks 9 to 24, and every 4 weeks thereafter for a maximum of 6 months of therapy. If subcutaneous formulation is available, participants can also receive subcutaneous daratumumab (1800 mg in 15 ml) in the same schedule.

  Also known as: Darzalex

• DrugBendamustine

  Bendamustine will be given at an initial dose of 100 mg/m\^2 intravenously on days 1 and 2 in each 28-day cycle.

  Also known as: Treanda

• DrugPomalidomide

  Pomalidomide will be administered at an initial dose of 2 mg per days on days 1-21 every 28 days.

  Also known as: Pomalyst

• DrugIxazomib

  Ixazomib will be administered at an initial dose of 4 mg per days on days 1, 8, and 15 every 28 days.

  Also known as: Ninlaro

• DrugVenetoclax MTD with Dexamethasone

  Venetoclax MTD (200 mg or 400 mg) with Dexamethasone (10 mg or 20 mg) as determined by the phase I results

Primary outcomes

1. Number of Participants with Dose Limiting Toxicities (DLT) (Phase 1)

   The number of participants with dose limiting toxicities for each treatment dose will be used to determine the MTD. Dose limiting toxicity defined as grade 4 neutropenia lasting more than 5 days, any grade febrile neutropenia, grade 4 thrombocytopenia, grade 3 thrombocytopenia with bleeding, other therapy related non-hematologic toxicity of grade 2 or higher that requires discontinuation of therapy, clinical tumor lysis syndrome (TLS), laboratory TLS if the metabolic abnormalities are considered clinically significant by the investigator. All other grade 3 or higher adverse events (AEs) will be considered as DLTs with a few exceptions.

   Time frame: Up to 6 cycles (approximately 6 months)

2. Hematologic ≥ Very Good Partial Response (VGPR) Rate (Phase 2)

   Hematologic ≥VGPR rate defined as proportion of participants achieving VGPR, low serum differential free light chain concentration (dFLC) partial response (PR), or a complete (CR). VGPR is defined as the difference between involved and uninvolved free light chain (FLC) \[dFLC\] \< 40 mg/L. Low dFLC PR is defined as achieving a dFLC\<10 mg/L, low dFLC PR will be considered as a deep hematologic response and included in the ≥VGPR category). CR is defined as negative serum and urine immunofixation electrophoresis along with a serum free light chain ratio that lies within the normal range or skewed towards the non-amyloid forming light chain, as per institutional laboratory values

   Time frame: Up to 6 cycles (approximately 6 months)

Secondary outcomes

1. Overall Organ Response Rate (ORR) (Phase 2)

   ORR defined as proportion of evaluable participants achieving organ response in each involved organ

   Time frame: Up to 1 year

2. Progression Free Survival (PFS) (Phase 2)

   PFS defined as time from the date of enrollment to hematologic progression or death, whichever is earlier

   Time frame: Up to 1 year

3. Overall Hematologic Response Rate (HRR) (Phase 2)

   HRR defined as proportion of patients achieving partial response (PR) or better

   Time frame: Up to 1 year

4. Duration of Hematologic Response (DOHR) (Phase 2)

   DOHR defined as time from the date of first documentation of hematologic response to the date of first documented hematologic disease progression

   Time frame: Up to 1 year

5. Time to hematologic ≥VGPR (Phase 2)

   Time to hematologic ≥VGPR defined as time from the first dose of study treatment to achievement of deep hematologic response (VGPR, low dFLC PR, or a CR)

   Time frame: Up to 1 year

6. Time to next treatment (TTNT) (Phase 2)

   TTNT defined as time from the date of enrollment to initiation of a subsequent line of therapy

   Time frame: Up to 1 year

7. Major Organ Deterioration-Progression Free Survival (MOD-PFS) (Phase 2)

   MOD-PFS defined as time from the date of enrollment to one of the following events (whichever occurs first): death, clinical manifestation of cardiac/renal failure, or development of hematologic progression of disease

   Time frame: Up to 1 year

8. Overall Survival (OS) (Phase 2)

   OS defined as the time from the date of enrollment to death from any cause

   Time frame: Up to 1 year

9. Patient-reported outcomes (PROs) (Phase 2)

   PROs defined as longitudinal score of "Physical Functioning" domain of Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Profile v2.0 The Physical Functioning domain contains four items with a 1 (unable to do) to 5 (without any difficulty) numeric rating.

   Time frame: Start of each cycle (Day 1 of each 28 day cycle) and Follow-up (every 8 weeks for up to 1 year)

Publications

• Locke M, Nieto M. AL Amyloidosis: Current Treatment and Outcomes. Adv Hematol. 2025 Mar 3;2025:7280805. doi: 10.1155/ah/7280805. eCollection 2025. PubMed 40226119 ↗