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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01985477
First received: November 8, 2013
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

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 (MM).

The safety of the drug combination will be studied in both phases.


Condition Intervention Phase
Myeloma
Drug: Lenalidomide
Drug: Dexamethasone
Drug: All-Trans Retinoic Acid (ATRA)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Lenalidomide (Revlimid), All-trans Retinoic Acid (ATRA) and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Lenalidomide/Dexamethasone and All-Trans Retinoic Acid (ATRA) [ Time Frame: 28 days ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Objective Response [ Time Frame: After 4, 28 day cycles ] [ Designated as safety issue: Yes ]
    The objective response (complete response + partial response) at 4 cycles is the primary endpoint. Patients assessed for response each cycle of therapy according to International Myeloma Working Group Criteria.


Estimated Enrollment: 70
Study Start Date: December 2013
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lenalidomide + Dexamethasone + All-Trans Retinoic Acid (ATRA)

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

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.

Other Names:
  • CC-5013
  • Revlimid
Drug: Dexamethasone

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.

Other Name: Decadron
Drug: All-Trans Retinoic Acid (ATRA)

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.

Other Names:
  • ATRA
  • Tretinoin (Oral)
  • Vesanoid
Experimental: Lenalidomide + All-Trans Retinoic Acid (ATRA)

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

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.

Other Names:
  • CC-5013
  • Revlimid
Drug: All-Trans Retinoic Acid (ATRA)

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.

Other Names:
  • ATRA
  • Tretinoin (Oral)
  • Vesanoid

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Understand and voluntarily sign an informed consent form
  2. Age >/= 18 years at the time of signing the informed consent form
  3. Serum creatinine </= 2.5 mg/dl OR Creatine clearance > 30 ml/min
  4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
  5. 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.
  6. Continuation from Inclusion #5: *A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
  7. Able to take prophylactic antiplatelet/anticoagulation, warfarin or equivalent agent
  8. Patient is able to understand and comply with the terms and conditions of the Lenalidomide Counseling Program.
  9. Phase I Specific Inclusion Criteria: Multiple myeloma that has progressed on lenalidomide and dexamethasone combination therapy at a dose of 25 mg daily on lenalidomide and 40 mg weekly of dexamethasone with measurable levels of myeloma paraprotein in serum ( >/= 0.5 g/dl), urine ( >/= 0.2 g excreted in a 24-hour collection sample), or abnormal free light chain (FLC) ratio.
  10. Phase I Specific Inclusion Criteria: Laboratory test results within these ranges: Absolute neutrophil count > 1000 cells/mm^3; Platelet count > 100,000 cells/mm^3 for patients with < 50% of bone marrow plasma cells and platelet count > 50,000 cells/mm^3 for patients in whom > 50% of the bone marrow nucleated cells were plasma cells; Total bilirubin </= 2.0 mg/dL; AST (SGOT) and ALT (AGPT) < 3 x upper limits of normal (ULN)
  11. Phase II Specific Inclusion Criteria: Cohort A: Multiple myeloma that has progressed on lenalidomide and dexamethasone combination therapy with measurable levels of myeloma paraprotein in serum ( >/= 0.5 g/dl), urine ( >/= 0.2 g excreted in a 24-hour collection sample), or involved FLC level by more than 10 mg/dL and abnormal free light chain (FLC) ratio. Cohort B: Multiple myeloma that has progressed on single agent lenalidomide therapy with measurable disease defined as: doubling of the M-component in 2 consecutive measurements in less than or equal to 2 months OR increase in serum M-protein levels by >/= .5g or urine protein by 200mg/24 hours, or involved FLC level by more than 10 mg/dL (with an abnormal FLC ratio).
  12. Phase II Specific Inclusion Criteria: Laboratory test results within these ranges: Absolute neutrophil count > 1000 cells/mm^3; Platelet count > 75,000 cells/mm^3 for patients with < 50% of bone marrow plasma cells and platelet count > 50,000 cells/mm^3 for patients in whom > 50% of the bone marrow nucleated cells were plasma cells; Total bilirubin </= 2.0 mg/dL; AST (SGOT) and ALT (AGPT) < 3 x ULN

Exclusion Criteria:

  1. Any serious medical condition, or psychiatric illness that would prevent the subject from signing the informed consent form.
  2. Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
  3. 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)
  4. Known hypersensitivity to lenalidomide or ATRA.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01985477

Contacts
Contact: Jatin J. Shah, MD 713-792-2860

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Celgene Corporation
Investigators
Principal Investigator: Jatin J. Shah, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01985477     History of Changes
Other Study ID Numbers: 2013-0624, NCI-2014-01098
Study First Received: November 8, 2013
Last Updated: June 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
All-Trans Retinoic Acid
Tretinoin (Oral)
Vesanoid
Myeloma
Multiple myeloma
MM
Relapsed/Refractory Multiple Myeloma
RR MM
Lenalidomide
CC-5013
Revlimid
Dexamethasone
Decadron
ATRA

Additional relevant MeSH terms:
Tretinoin
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Lenalidomide
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on October 19, 2014