Revlimid / All-Trans Retinoic Acid (ATRA) / Dexamethasone in Relapsed/Refractory Multiple Myeloma

NCT01985477 | Terminated Phase 1

• 2 other identifiers: 2013-0624NCI-2014-01098
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of the Phase I portion of this clinical research study is to find the highest tolerated dose of the combination of lenalidomide, all-trans retinoic acid (ATRA), and dexamethasone that can be given to patients with relapsed or refractory multiple myeloma (MM). The goal of the Phase II portion of this study is to learn if ATRA when given in combination with lenalidomide alone or with lenalidomide and dexamethasone can help to control multiple myeloma. In September 2015, the study was terminated due to slow accrual while still a Phase I study, no additional registration or research performed under the Phase II portion of the study.

Conditions

Myeloma

Keywords

Myeloma; Multiple myeloma; MM; Relapsed/Refractory Multiple Myeloma; RR MM; Lenalidomide; CC-5013; Revlimid; Dexamethasone; Decadron; All-Trans Retinoic Acid; ATRA; Tretinoin (Oral); Vesanoid

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Lenalidomide/Dexamethasone and All-Trans Retinoic Acid (ATRA)

  MTD defined as highest dose level in which 6 patients have been treated with less than 2 instances of dose limiting toxicity (DLT). Dose limiting toxicity refers to a medically significant event which meets one of the following: Hematologic dose-limiting toxicity defined as either, Grade 4 neutropenia lasting for \>/=14 days in duration ( growth factors permitted after DLT established), Grade 4 thrombocytopenia \> 14 days despite platelet transfusions. Non-hematologic DLT defined as any Grade 3, 4 or 5 non-hematologic toxicity, with the specific exception of, Isolated Grade 3 elevation of liver function tests (LFTs) without associated clinical symptoms, lasting for \</=7 days in duration, Isolated Grade 3 elevation of amylase without associated clinical symptoms, Grade 3 hypocalcemia, hyperglycemia, hypokalemia, hypomagnesemia, hyponatremia, or hypophosphatemia which responds to medical intervention.

  28 days

Secondary Outcomes (1)

• Objective Response

  After 4, 28 day cycles

Study Arms (2)

Lenalidomide + Dexamethasone + All-Trans Retinoic Acid (ATRA)

EXPERIMENTAL

Phase I All Patients - Induction: Lenalidomide starting dose 25 mg by mouth 1 time every day on Day 1-21. Dexamethasone starting dose 40 mg by mouth on Days 1,8,15,22. ATRA starting dose 25 mg/m2 by mouth 2 times each day on Days 1-21. Phase II Group A: Lenalidomide starting dose: Dose tolerated prior to enrollment. Dexamethasone starting dose: Dose previously on when progressing prior to study entry. ATRA starting dose: MTD from Phase I. Maintenance Therapy Group A: Lenalidomide at dose level tolerated at completion of cycle 3 for 21/28 days, with ATRA at dose determined in Phase I for 14/28 days, and Dexamethasone at last tolerated dose on Days 1, 8, 15 and 22. After 3 months on therapy at MTD in Phase I study, patients must be switched to this dose schedule. Patients unable to tolerate either Dexamethasone during maintenance phase may dose reduce Dexamethasone as needed.

Drug: Lenalidomide; Drug: Dexamethasone; Drug: All-Trans Retinoic Acid (ATRA)

Lenalidomide + All-Trans Retinoic Acid (ATRA)

EXPERIMENTAL

Phase II Group B: Lenalidomide will be given as a single oral dose at the level patient was on at the time of progression on single agent Lenalidomide prior to study enrollment. All-Trans Retinoic Acid (ATRA) starting dose: MTD from Phase I. Maintenance Therapy: Maintenance therapy consists of lenalidomide at the dose level tolerated at the completion of cycle 3 for 21/28 days, with ATRA at the dose determined in the phase I portion of the trial for 14/28 days. Dexamethasone will not be administered. After 3 months on therapy at the MTD in the phase 1 study, patients must be switched to this dose schedule.

Drug: Lenalidomide; Drug: All-Trans Retinoic Acid (ATRA)

Interventions

Lenalidomide DRUG

Phase I All Patients - Induction: Lenalidomide starting dose 25 mg by mouth 1 time every day on Day 1-21. Phase II Group A: Lenalidomide starting dose: Dose tolerated prior to enrollment. Maintenance Therapy: Phase I and Phase II Group A: Maintenance therapy lenalidomide at dose level tolerated at completion of cycle 3 for 21/28 days. Phase II Group B: Lenalidomide will be given as a single oral dose at the level patient was on at the time of progression on single agent lenalidomide prior to study enrollment.

Also known as: CC-5013, Revlimid

Lenalidomide + All-Trans Retinoic Acid (ATRA); Lenalidomide + Dexamethasone + All-Trans Retinoic Acid (ATRA)

Dexamethasone DRUG

Phase I All Patients - Induction: Dexamethasone starting dose 40 mg by mouth on Days 1,8,15,22. Phase II Group A: Dexamethasone starting dose: Dose previously on when progressing prior to study entry. Maintenance Therapy: Phase I and Phase II Group A: Dexamethasone at last tolerated dose on Days 1, 8, 15 and 22.

Also known as: Decadron

Lenalidomide + Dexamethasone + All-Trans Retinoic Acid (ATRA)

All-Trans Retinoic Acid (ATRA) DRUG

Phase I All Patients - Induction: ATRA starting dose 25 mg/m2 by mouth 2 times each day on Days 1-21. Phase II Group A: ATRA starting dose: MTD from Phase I. Maintenance Therapy: Phase I and Phase II Group A: ATRA at dose determined in Phase I for 14/28 days. Phase II Group B: All-Trans Retinoic Acid (ATRA) starting dose: MTD from Phase I. Maintenance Therapy Group B: ATRA at the dose determined in the Phase I portion of the trial for 14/28 days.

Also known as: ATRA, Tretinoin (Oral), Vesanoid

Lenalidomide + All-Trans Retinoic Acid (ATRA); Lenalidomide + Dexamethasone + All-Trans Retinoic Acid (ATRA)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Understand and voluntarily sign an informed consent form
• Age \>/= 18 years at the time of signing the informed consent form
• Serum creatinine \</= 2.5 mg/dl OR Creatine clearance \> 30 ml/min
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
• Females of childbearing potential (FCBP)\* must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mlU/mL within 10-14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional affective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a female of childbearing potential even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
• Able to take prophylactic antiplatelet/anticoagulation, warfarin or equivalent agent
• Patient is able to understand and comply with the terms and conditions of the Lenalidomide Counseling Program.

You may not qualify if:

• Any serious medical condition, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
• Use of any cancer therapy within 14 days prior to beginning cycle 1 day 1 of therapy with the exception of lenalidomide and dexamethasone (radiation therapy allowed within 5 days of completion of radiation therapy)
• Known hypersensitivity to lenalidomide or ATRA.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Celgene Corporation: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Neoplasms, Plasma Cell; Multiple Myeloma

Interventions

Lenalidomide; Dexamethasone; Calcium Dobesilate; Tretinoin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors

Study Officials

• Jatin J. Shah, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2013
• First Posted: November 15, 2013
• Study Start: December 1, 2013
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: September 14, 2016

Record last verified: 2016-09

Locations

US (1)